Characteristics, Classification, and Application of Stem Cells Derived from Human Teeth

Lei, Tong; Zhang, Xiaoshuang; Du, Hongwu

doi:https://doi.org/10.1155/2021/8886854

Stem Cells International

On this page

Abstract Introduction Discussion and Conclusions Abbreviations Conflicts of Interest Acknowledgments References Copyright Related Articles

Review Article | Open Access

Volume 2021 | Article ID 8886854 | https://doi.org/10.1155/2021/8886854

Characteristics, Classification, and Application of Stem Cells Derived from Human Teeth

Tong Lei,^1,2Xiaoshuang Zhang,^1,2and Hongwu Du^1,2

Academic Editor: Andrea Ballini

Received15 Sept 2020

Revised12 Feb 2021

Accepted07 May 2021

Published31 May 2021

Abstract

Since mesenchymal stem cells derived from human teeth are characterized as having the properties of excellent proliferation, multilineage differentiation, and immune regulation. Dental stem cells exhibit fibroblast-like microscopic appearance and express mesenchymal markers, embryonic markers, and vascular markers but do not express hematopoietic markers. Dental stem cells are a mixed population with different sensitive markers, characteristics, and therapeutic effects. Single or combined surface markers are not only helpful for understanding the subpopulation of mixed stem cell populations according to cell function but also for improving the stable treatment effect of dental stem cells. Focusing on the discovery and characterization of stem cells isolated from human teeth over the past 20 years, this review outlines the effect of marker sorting on cell proliferation and differentiation ability and the assessment of the clinical application potential. Classified dental stem cells from markers and functional molecules can solve the problem of heterogeneity and ensure the efficacy of cell therapy strategies including dentistry, neurologic diseases, bone repair, and tissue engineering.

1. Introduction

Due to the advantages in immune privilege, ethical approval, and easy accession, mesenchymal stem cells are receiving increasing attention in medical research. Mesenchymal stem cells (MSCs) can be isolated from multiple human organs or tissues, such as umbilical cord blood, bone marrow, adipose tissue, and brain tissue. Dental stem cells are a kind of mesenchymal stem cells and can be obtained by specific methods, separating tissues around human teeth. So far, eight types of dental stem cells were successfully isolated, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), apical papilla stem cells (SCAP), periodontal ligament stem cells (PDLSCs), dental follicle stem cells (DFSCs), gingival mesenchymal stem cells (GMSCs), human tooth germ stem cells (TGPCs), and alveolar bone mesenchymal stem cells (ABMSCs) [1–3].

Obtaining the stability of the stem cell transplantation treatment effect has always been the core issue of clinical treatment [4–6]. The most fundamental problem is how to control the quality and efficacy of cell populations in regenerative medicine. This means that the safety of stem cell treatments can only be guaranteed by addressing cell population heterogeneity. However, even the subgroup of stem cells isolated from human teeth has significant differences in cell properties, such as proliferation and differentiation. Therefore, how to identify and characterize dental stem cells is an essential point in basic research, but the systematic discussion is lacking. This review attempted to combine the surface markers with the differentiation ability of eight types of dental stem cells and understand the feature of preclinical applications.

2. Dental Pulp Stem Cells

In 2000, inspired by the extraction of human bone marrow stromal cells (BMSCs), dental pulp stem cells (DPSCs) were first isolated from adult human dental pulp. DPSCs showed fibroblast-like cell morphology in Eagle’s medium and a high colony formation activity as colony-forming unit-fibroblasts (CFU-F) (Figure 1) [7]. Surface marker analysis indicated that DPSCs were positive for CD29, CD44, CD73, CD90, CD105, CD117, CD146, CD271, CD166, and STRO-1, but negative for CD11b, CD14, CD19, CD34, CD45, CD79, CD106, and HLA-DR (Table 1) [8–12]. DPSCs were widely used in various clinical applications of regenerative medicine including dentin regeneration, treatment of retinal degeneration, spinal cord injuries, Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, myocardial infarction, muscular dystrophy, and diabetes and immune diseases [13–16].

2.1. CD34, CD45, and c-Kit

CD34, CD45, and c-kit (CD117) are the markers of hematopoietic stem cells (HSCs). It has been found that CD34 is related to the short-term reproduction capacity and the formation of cell clones [17–19]. After planted in dental scaffolds, CD34 + DPSCs showed excellent biocompatibility, high proliferation viability, osteogenic differentiation, and high abundance of VEGF. This indicated that CD34 could be used as a marker to select DPSCs for subgroups that have the potential to become dental materials. CD45 is involved in proliferation and myogenic capacity [20, 21]. c-Kit is a receptor for stem cell factor (SCF) and c-kit+ HSCs can proliferate in response to hematopoietic factors [22, 23]. In enrichment analysis, these membrane molecules (CD34, CD45, and c-kit) are involved in cell adhesion, vasculature and bone development, cell proliferation, and stem cell differentiation. Populations of cells expressing CD34 and CD45, c-kit were identified as the first landmark in the evaluation of DPSCs. The c-kit+/CD34+/CD45-DPSCs that has high proliferation characteristics can not only differentiate into osteoblasts but also produce active autologous fibrous bone (LAB) tissue in vitro, which can form layered bone after being transplanted into immunodeficient rats [24].

2.2. STRO-1

The antibody of STRO-1 was found to bind to monocytes, and it can specifically identify antigens on perivascular cells in bone marrow and dental pulp tissues. STRO-1+ cell populations appeared to form CFU-F [25–27]. The expression of CD34 in DPSCs was controversial. STRO-1+/c-Kit/CD34- and STRO-1+/c-Kit+/CD34+ cells were similar in their differentiation capabilities. However, compared to STRO-1+/c-Kit+/CD34+ cells, STRO-1+/c-Kit+/CD34- cells proliferated faster and had less senescence and apoptosis. On the contrary, the STRO-1+/c-Kit+/CD34+ DPSCs expressed the typical neuronal markers, including CD271 and Nestin, and had a tendency toward neural differentiation [26]. STRO-1+/c-Kit+/CD34+ DPSCs are considered as a promising source of stem cells for the treatment of demyelinating disorders, which can improve the functional recovery of sciatic nerve defect in rats [28].

2.3. CD90 and CD271

CD90 is positive in mesenchymal progenitor cells but negative in skin fibroblasts. Based on the active screening of CD90, it was found that CD45-/CD90+ population showed a higher floating fat fraction and had a significant correlation with the frequencies of CFU-F [29–31]. CD271 expression is a screening criterion for hematopoietic progenitor cells. The CD34+/CD271+ population has high cloning activity [32]. CD90+/CD271+ DPSC subpopulations are able to form high-density cell populations. These subpopulations have the potential for long-term proliferation and multilineage differentiation. Hence, they can promote the formation of new bones and treat skull defects [33]. The cell surface hydrolase tissue nonspecific alkaline phosphatase (TNAP) (also known as MSCA-1), coexpressed with CD73 and CD90, is a potentially useful marker for DPSC selection, especially for mineralized tissue regenerative therapies [34]. CD271 is regarded as a marker of oral cells originating from the neural crest. This surface marker shows adipogenesis, cartilage formation, myogenic, and osteogenic potential of DPSCs [33, 35]. CD271-DPSCs display higher proliferation rates compared with CD271+ DPSCs [36].

3. Stem Cells from Human Exfoliated Deciduous Teeth

In 2003, stem cells from human exfoliated deciduous teeth (SHED) were isolated from normal detached incisors (Figure 1). Holistically, it is found that SHED express MSC-like antigens such as CD29, CD44, CD63, CD71, CD73, CD90, CD105, CD117, and CD146, CD166 as well as the embryonic stem cell markers OCT3/4, NANOG, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81, and progenitor cell markers CD13, CD31. Meanwhile, SHED do not express CD11b, CD14, CD18, CD19, CD31, CD34, CD45, CD49d, CD49e, CD106, CD133, CD184, CD197, and HLA-DR (Table 1) [37–40]. SHED can be induced into multilineage differentiation cell types including dopaminergic neurons, odontoblasts, osteoblasts, chondrocytes, adipocytes, liver cells, skin cells, and endothelial cells. SHED is a potential cell source in clinical applications such as dental regenerative, bone regeneration, intractable pediatric surgical diseases, liver failure, neural regeneration, and the revascularization for therapeutic applications [41–45].

3.1. CD105

CD105 (also known as Endoglin) is one of the positive markers of HSCs and skeletal-muscle-derived stem cells. CD105 can also promote the production of bone marrow and red blood cells, and regulate hematopoietic development of specific lineages. Besides, CD105+ MSCs have the adipogenesis and osteogenesis potential [46, 47]. In addition, CD105 is closely related to hereditary hemorrhagic telangiectasia and may be involved in preeclampsia, type 2 diabetes, and several types of cancer [48–51]. CD105 was validated in its ability to allow select and enrich for SHED in many studies, and CD105+ subpopulations in SHED have higher osteogenic potential in vitro. In addition, hsa-mir-1287 regulates CD105 expression and controls osteopotential in SHED by fine-tuning hsa-mir-1287 levels [52].

3.2. CD146

CD146, also known as MUC18, is a cell adhesion molecule. CD146+ MSCs tend to form bones, and the bone-forming ability will be downregulated in hypoxia [53, 54]. CD146 is often used as a marker to diagnose diseases such as systemic sclerosis, colorectal cancer, and breast cancer and as a target for immunotherapeutic treatment against osteosarcoma [55–57]. To obtain CD146+ and CD146- subpopulations of SHED, the magnetically activated cell sorting (MACS) was applied. The CD146 + SHED favors the differentiation of osteoblasts and glial and the negative subpopulation prefers adipogenic and neuronal differentiation [58]. Priming with FGF-2 is an effective way to increase the proportion of CD146+ cells in SHED [43].

4. Stem Cells from the Apical Papilla

Stem cells from the apical papilla (SCAP) were extracted from human immature permanent teeth in 2006 (Figure 1). SCAP is positive for CD24, CD29, CD34, CD45, CD73, CD90, CD105, CD106, CD146, CD166, and STRO-1 and negative for CD18, CD34, CD44, CD49f, CD81, CD117, and CD150 (Table 1) [59, 60]. SCAP shows immunosuppressive properties, which expand the application of SCAP in regeneration medicine, including immunotherapy and the reparation of multiple tissues (such as teeth, bone, nerve, and vascular tissue) [61].

4.1. CD24

CD24 is proposed as a specific surface marker, which can distinguish SCAP from DPSCs and BMSCs [60]. CD24 is strongly expressed in SCAP regardless of whether the tissue is inflamed or not, and one of the markers for multilineage stem cells in screening stable proliferation and differentiation populations [62, 63]. Moreover, CD24 shows a high abundance in the early stages of root development. It was found that high-CD24 expressing SCAP showed poor renewal ability but showed stronger osteogenic differentiation ability than low-CD24 expressing SCAP [64].

4.2. STRO-1 and CD146

One of the evidences for the presence of stem cells in the apical papilla was the positive expression of STRO-1 [65]. The positive expression of CD146 in SCAP is still controversial. The CD146+/STRO-1+ SCAP cell population was observed morphologically bigger with greater granularity in flow cytometry. Filtering by multiple marker combinations, the STRO-1+/CD146+ subpopulation was found to have a better potential for embryonic, mesenchymal, and odontogenic differentiation compared with the STRO-1-/CD146+ subpopulation [66, 67].

5. Periodontal Ligament Stem Cells

A cell population was collected by dissolving the periodontal ligament from a third molar of a 16-19-year-old human tooth to obtain a dispersed cell suspension, which could express MSC markers and differentiate into dentin cells, adipocytes, and collagen cells under special support nourishment. After transplantation, the cells were able to help rodents repair periodontal tissue, so the population was named as periodontal ligament stem cells (PDLSCs) (Figure 1). PDLSCs exhibited high expression of CD9, CD10, CD13, CD29, CD34, CD38, CD44, CD49d, CD59, CD73, CD90, CD105, CD106, CD146, CD166, and STRO-1, and lack of CD14, CD117, CD133, CD144, CD309, and HLA-DR (Table 1) [68–73]. PDLSCs can be physically stimulated to regulate proliferation and differentiation by activating different signaling pathways including MAPK, TGF/Smad, and Wnt/catenin pathways. This characteristic, PDLSCs fate to physical force in vitro and orthodontic force in vivo, determines that PDLSCs are a natural periodontal regeneration material in orthodontic tooth movement [74, 75].

5.1. STRO-1 and CD146

The STRO-1+/CD146+ PDLSCs population appears to be a unique cell population in humans while there are no such cells in mice [76]. Immunochemical staining is applied for STRO-1 and CD146 expression in PDLSCs. STRO-1+ PDLSCs can form colonies, which indirectly demonstrate that STRO-1 is an early progenitor cell marker for PDLSCs. Determined by flow cytometry, STRO-1+/CD146+ cells account for 2.6% of the population, and STRO-1-/CD146- cells account for more than 63% of PDLSCs. STRO-1+/CD146+ PDLSCs can form mineralized nodules, lipid vacuoles, and cartilage macromolecules after being induced under certain condition, demonstrating potent multilineage differentiation potential [69]. The outstanding ability to differentiate into the cartilage of STRO-1+/CD146+ PDLSCs making this population is a promising alternative material for cartilage regeneration.

5.2. CD271

CD271 plays an important role in tooth development and epithelial-mesenchymal transition (EMT). It is used as a universal receptor for neurotrophins to stimulate neuronal cell survival and differentiation [77, 78]. CD271+ PDLSCs demonstrate strong mineralization capabilities with the high expression of osteogenic markers such as DLX5, RUNX2, and BGLAP. CD271+ PDLSCs can be used as a promising bone regeneration material due to its excellent osteogenic differentiation ability. CD271 does not coexpress with CD90 and CD146, so it is used as a sole marker for sorting in PDLSCs [79].

6. Dental Follicle Stem Cells

Dental follicle stem cells (DFSCs) are separated from the tissue of the human dental follicle. Genes of FGFR1-IIIC, IGF-2, collagen 1, OCN, BS, and IGF-2 are more strongly expressed by the human DFSCs than in MSCs (Figure 1) [80]. Characterization of DFSCs reveals high expression of CD9, CD10, CD13, CD29, CD44, CD49d, CD56, CD59, CD90, CD105, CD106, CD166, and STRO-1 and poor expression of CD3, CD31, CD33, CD34, CD45, CD133, and CD271 (Table 1) [80–83]. DFSCs demonstrate the ability to differentiate multiple-lineages, such as osteoblastic/cementoblastic and neural lineages [84, 85].

6.1. CD68 and CD117

CD68 and CD117 are markers expressed by endothelial cells, and CD68 is a human macrophage marker [86]. CD117+ DFSCs may be involved in the signal transmission between cells during tooth germ development [87]. The expression of CD68 in DFSCs does not mean the presence of inflammatory cells. On the contrary, CD68+ DFSCs maintain a local hematopoietic stem niche. CD117+/CD68+ DFSCs can be used to identify endothelial progenitor cells and is related to a myeloid and progenitor phenotype in the human dental follicle. Meanwhile, the subsets are able to form neovessels and play a hematopoietic role [88].

7. Gingiva-Derived Mesenchymal Stem Cells

Gingiva-derived mesenchymal stem cells (GMSCs) are MSCs that reside in human gingival tissues (Figure 1). GMSCs express markers including CD13, CD44, CD73, CD90, CD105, CD146, CD166, CD271, and STRO-1, and not express CD14, CD19, CD34, CD38, CD45, and CD54 (Table 1) [89–94]. GMSCs maintain normal karyotype and telomerase activity in long-term in vitro, showing good clinical safety [95].

7.1. CD39 and CD73

CD39 and CD73 are coexpressed on GMSCs and regulate T cells, which play a catalytic role to promote immune regulation and reduce inflammation [96, 97]. CD39 and CD73 are involved in the formation of osteoclasts in GMSCs and significantly attenuate the severity of arthritis in vivo and in vitro [98]. Simultaneously, in the experiment of cotransplantation of GMSCs and PBMC in the NOD/SCID mouse, it was found that GMSCs suppressed the immune response through the CD39/CD73 pathway to relieve graft-versus-host disease (GVHD). It shows that CD39/CD73 can be used as a marker to evaluate the therapeutic effect of GMSCs on autoimmune diseases [99, 100].

8. Tooth Germ Progenitor Cells

A new type of dental stem cell was isolated and named as the tooth germ progenitor cells (TGPCs) in 2008 (Figure 1). RT-PCR and flow cytometry analysis tentatively suggest that TGPCs are positive expression of CD29, CD44, CD73, CD90, CD105, and CD166, and extremely negative expression of STRO-1, CD14, CD34, CD45, CD133, and HLA-DR (Table 1) [101–103]. TGPCs are able to differentiate into muscle, cartilage, fat, nerve, bone, and tooth, and it is an alternative material in regenerative medicine [104].

8.1. STRO-1

STRO-1 is positively expressed in TGPCs, and the subpopulation shows remarkable osteogenic differentiation ability. SRTO-1+ TGPCs exhibit strong mineralization with high expression of the osteogenic gene including OCT4, SOX2, MYC, and NANOG. STRO-1 can be used to evaluate the feasibility of TGPCs application in bone regeneration material [105, 106].

9. Alveolar Bone-Derived Mesenchymal Stem Cells

In 2005, alveolar bone mesenchymal stem cells (ABMSCs) were obtained from surgery on 6 to 44-year-old patients (Figure 1). ABMSCs are found to have sufficiently high proliferative capacity and myogenic potential. ABMSCs are positive expressions of CD29, CD44, CD73, CD90, CD105, CD146, and STRO-1, and negative for CD11b, CD19, CD31, CD34, CD45, and CD324 (Table 1) [107–110]. Protein arrays were used to identify the contents of ABMSCs and found that ABMSCs expressed IL-6 and MCP-1. ABMSCs are able to inhibit the activation and proliferation of monocytes and T cells after cocultured with different types of immune cells including THP-1 monocytes, macrophages, and peripheral blood mononuclear cell (PBMCs). Therefore, ABMSCs are a viable cell source for treating inflammation [111].

10. Regenerative Application of Dental Stem Cells

Dental stem cells are a potential enhancer of regenerative medicine in the future. Oral tissue repair and regeneration are the most widely clinical applications of stem cells in clinical trials (https://clinicaltrials.gov/ct2/home), including dental pulp regeneration, periodontal disease, peripical, periodontitis, knee osteoarthritis, dental plaque, alveolar bone atrophy, root canal therapy, and endodontic disease [112–114]. The use of biomaterials can enhance the efficiency of osteogenic differentiation in vitro and in vivo, including hydroxyapatite-tricalcium phosphate (HA-TCP) and demineralized dentin matrix (DDM) [115]. Dental stem cells can be induced into osteogenic, adipogenic, and neural differentiation in a specific medium [116]. Dental stem cells with pretreatment are an effective material such as in neurodegenerative diseases. Neuron-like stem cell transplantation can exert a stable and significant effect in brain diseases, which involves the activation of Wnt/β-catenin signaling, Rho kinase, and AKT/GSK3β signaling pathway [117–119].

The safety of stem cell transplantation is the primary requirement for cell transplantation [120]. The tumorigenicity of cell transplantation must be checked in clinical trials. Although the safety of dental stem cells has not been questioned, every clinical application should ensure safety under long-term monitoring and large-scale samples [121]. Few clinical records of dental stem cells have been retrieved, so the safety of human trials needs to be constantly monitored [122].

Due to the uncertainty of the timeliness of cell transplantation in vivo, the injection method is one of the factors that affect the therapeutic effect, including systemic injection and local injection [123]. Injection in the lesion area is one of the common ways to improve the effectiveness of cell transplantation, but it is not suitable for systemic diseases and chronic diseases [124, 125].

Why can cells improve symptoms and cure diseases? This is the most urgent problem to be solved in future research. The explanation of the mechanism of action can not only find safe and effective disease treatment drugs but also help to understand the pathogenesis of the disease [126]. Complex networks exist in the mechanism of various diseases, but the selection of key nodes needs to be supported by huge work.

11. Discussion and Conclusions

Since the beginning of the 21st century, stem cells isolated from teeth have been continuously discovered and reported. Dental stem cells exhibit outstanding neural differentiation and immune characteristics due to the neural crests origin. Ethical concerns regarding dental stem cells are not an issue, and the resolution of heterogeneity problems can help improve their performance and expand their applications [127]. One significant defect of stem cells isolated in vitro is the heterogeneity of the cell population. One of the main manifestations is the instability of the source of cellular materials, including the characteristics of surface markers and the ability to differentiate. On the other hand, the unstable treatment effect of stem cell transplantation is the biggest limitation of clinical application [128].

To supplement the practical requirement of allogeneic stem cell transplantation, the screening and identification of markers in dental stem cells have been widely carried out from different donors [129]. The analysis of stem cell contents and the composition of membrane molecules is one way to solve this problem. Proteomics has been applied to the characterization of stem cells, including two-dimensional electrophoresis, iTRAQ or TMT-labeled quantitative proteomics, and nanomass spectrometry [129–131]. However, studies have rarely analyzed the essential differences in one individual by omics analyses. Subsequent studies should concentrate on the differential expression of cells from the same donor [132].

Stem cell subpopulation studies will enable the control of stem cell heterogeneity by flow cytometry or sorting via magnetic beads. Membrane surface markers cannot represent functional cell populations. Stem cells capable of treating diseases should be characterized by functional molecules, which may be involved in metabolic physiological processes and signaling pathways to participate in pathogenesis and development [73, 105]. Surface molecules are used as markers to sort stem cell subsets. The proliferation and differentiation potential of subsets can be analyzed separately. Therefore, a sole marker or a combination of multiple markers separates a subset of cells with different characteristics [47, 50, 52, 54, 57, 67].

Stem cell-derived extracellular vesicles (EVs) are favored as an alternative to cell transplantation [133, 134]. EVs, including RNA, protein, and lipid metabolites, are able to circulate in the blood and cross the blood-brain barrier [135, 136]. EVs are considered to be functional vesicles and participate in disease regulation and are used as drug carriers [137, 138]. EVs secreted from DPSCs promote the formation of blood vessels and release of VEGF in vitro [139, 140]. It is believed that EVs can become potential clinical materials.

In conclusion, dental stem cells as a dental material have become a promising tool for solving oral clinical problems. The heterogeneity of dental stem cell populations severely hampers the process of elucidating their mechanisms of action. A sole marker or a combination of multiple markers is used to identify stem cells derived from teeth, which is an effective method to solve the problem of heterogeneity. In summary, the marker of stem cells is the first stage to ensure the effectiveness of cell therapy. Sole marker and associated markers of stem cells play an essential role in cell characterization in clinical applications. The resolution of heterogeneity problems can help improve performance and expand applications of dental stem cells.

Abbreviations

MSCs:	Mesenchymal stem cells
DPSCs:	Dental pulp stem cells
SHED:	Stem cells from human exfoliated deciduous teeth
SCAP:	Stem cells from the apical papilla
PDLSCs:	Periodontal ligament stem cells
DFSCs:	Dental follicle stem cells
GMSCs:	Gingiva-derived mesenchymal stem cells
TGPCs:	Tooth germ progenitor cells
ABMSCs:	Alveolar bone-derived mesenchymal stem cells
BMSCs:	Human bone marrow stromal cells
HSCs:	Hematopoietic stem cells
VEGF:	Vascular endothelial growth factor
HLA-DR:	Human leukocyte antigen-DR
iTRAQ:	Isobaric tags for relative and absolute quantitation
GVHD:	Graft-versus-host disease
CFU-F:	Colony-forming unit-fibroblasts.

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this manuscript.

Acknowledgments

This work was supported by the Hebei Provincial Department of Science and Technology (No. 19942410G).

References

J. Liu, F. Yu, Y. Sun et al., “Concise reviews: characteristics and potential applications of human dental tissue-derived mesenchymal stem cells,” Stem Cells, vol. 33, no. 3, pp. 627–638, 2015.
View at: Publisher Site | Google Scholar
A. Mantesso and P. Sharpe, “Dental stem cells for tooth regeneration and repair,” Expert Opinion on Biological Therapy, vol. 9, no. 9, pp. 1143–1154, 2009.
View at: Publisher Site | Google Scholar
C. Morsczeck and T. E. Reichert, “Dental stem cells in tooth regeneration and repair in the future,” Expert Opinion on Biological Therapy, vol. 18, no. 2, pp. 187–196, 2018.
View at: Publisher Site | Google Scholar
M. Lei, K. Li, B. Li, L.-N. Gao, F.-M. Chen, and Y. Jin, “Mesenchymal stem cell characteristics of dental pulp and periodontal ligament stem cells after _in vivo_ transplantation,” Biomaterials, vol. 35, no. 24, pp. 6332–6343, 2014.
View at: Publisher Site | Google Scholar
W. C. Shen, Y. C. Lai, L. H. Li et al., “Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis,” Nature Communications, vol. 10, no. 1, p. 2226, 2019.
View at: Publisher Site | Google Scholar
K. Xuan, B. Li, H. Guo et al., “Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth,” Science Translational Medicine, vol. 10, no. 455, p. eaaf3227, 2018.
View at: Publisher Site | Google Scholar
S. Gronthos, M. Mankani, J. Brahim, P. G. Robey, and S. Shi, “Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 25, pp. 13625–13630, 2000.
View at: Publisher Site | Google Scholar
C. Gandia, A. Armiñan, J. M. García-Verdugo et al., “Human Dental Pulp Stem Cells Improve Left Ventricular Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute Myocardial Infarction,” Stem Cells, vol. 26, no. 3, pp. 638–645, 2008.
View at: Publisher Site | Google Scholar
G. T. Huang, S. Gronthos, and S. Shi, “Mesenchymal Stem Cells Derived from Dental Tissues vs. Those from Other Sources: Their Biology and Role in Regenerative Medicine,” Journal of Dental Research, vol. 88, no. 9, pp. 792–806, 2009.
View at: Publisher Site | Google Scholar
Y. Y. Jo, H. J. Lee, S. Y. Kook et al., “Isolation and characterization of postnatal stem cells from human dental tissues,” Tissue Engineering, vol. 13, no. 4, pp. 767–773, 2007.
View at: Publisher Site | Google Scholar
E. Machado, M. H. Fernandes, and P. S. Gomes, “Dental stem cells for craniofacial tissue engineering,” Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, vol. 113, no. 6, pp. 728–733, 2012.
View at: Publisher Site | Google Scholar
A. Uccelli, L. Moretta, and V. Pistoia, “Mesenchymal stem cells in health and disease,” Nature Reviews Immunology, vol. 8, no. 9, pp. 726–736, 2008.
View at: Publisher Site | Google Scholar
H. A. Alsaeedi, C. Lam, A. E.-H. Koh et al., “Looking into dental pulp stem cells in the therapy of photoreceptors and retinal degenerative disorders,” Journal of Photochemistry and Photobiology B: Biology, vol. 203, p. 111727, 2020.
View at: Publisher Site | Google Scholar
A. Pisciotta, L. Bertoni, A. Vallarola, G. Bertani, D. Mecugni, and G. Carnevale, “Neural crest derived stem cells from dental pulp and tooth-associated stem cells for peripheral nerve regeneration,” Neural Regeneration Research, vol. 15, no. 3, pp. 373–381, 2020.
View at: Publisher Site | Google Scholar
X. Shi, J. Mao, and Y. Liu, “Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications,” STEM CELLS Translational Medicine, vol. 9, no. 4, pp. 445–464, 2020.
View at: Publisher Site | Google Scholar
Y. Yamada, S. Nakamura-Yamada, K. Kusano, and S. Baba, “Clinical Potential and Current Progress of Dental Pulp Stem Cells for Various Systemic Diseases in Regenerative Medicine: A Concise Review,” International Journal of Molecular Sciences, vol. 20, no. 5, p. 1132, 2019.
View at: Publisher Site | Google Scholar
M. J. Borowitz, J. J. Shuster, C. I. Civin et al., “Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study,” Journal of Clinical Oncology, vol. 8, no. 8, pp. 1389–1398, 1990.
View at: Publisher Site | Google Scholar
C. Elliott, D. M. Samson, S. Armitage et al., “When to harvest peripheral-blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34-positive concentration in peripheral blood,” Journal of Clinical Oncology, vol. 14, no. 3, pp. 970–973, 1996.
View at: Publisher Site | Google Scholar
M. Osawa, K. Hanada, H. Hamada, and H. Nakauchi, “Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell,” Science, vol. 273, no. 5272, pp. 242–245, 1996.
View at: Publisher Site | Google Scholar
A. Polesskaya, P. Seale, and M. A. Rudnicki, “Wnt Signaling Induces the Myogenic Specification of Resident CD45⁺ Adult Stem Cells during Muscle Regeneration,” Cell, vol. 113, no. 7, pp. 841–852, 2003.
View at: Publisher Site | Google Scholar
S. Taoudi, C. Gonneau, K. Moore et al., “Extensive hematopoietic stem cell generation in the AGM region via maturation of VE-cadherin+CD45+ pre-definitive HSCs,” Cell Stem Cell, vol. 3, no. 1, pp. 99–108, 2008.
View at: Publisher Site | Google Scholar
J. Lennartsson and L. Ronnstrand, “Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications,” Physiological Reviews, vol. 92, no. 4, pp. 1619–1649, 2012.
View at: Publisher Site | Google Scholar
M. Ortiz, J. W. Wine, N. Lohrey, F. W. Ruscetti, S. E. Spence, and J. R. Keller, “Functional characterization of a novel hematopoietic stem cell and its place in the c-kit maturation pathway in bone marrow cell development,” Immunity, vol. 10, no. 2, pp. 173–182, 1999.
View at: Publisher Site | Google Scholar
G. Laino, R. D'Aquino, A. Graziano et al., “A new population of human adult dental pulp stem cells: a useful source of living autologous fibrous bone tissue (LAB),” Journal of Bone and Mineral Research, vol. 20, no. 8, pp. 1394–1402, 2005.
View at: Publisher Site | Google Scholar
Y. A. Cho, D. S. Kim, M. Song, W. J. Bae, S. Lee, and E. C. Kim, “Protein interacting with never in mitosis A-1 induces glutamatergic and GABAergic neuronal differentiation in human dental pulp stem cells,” Journal of Endodontia, vol. 42, no. 7, pp. 1055–1061, 2016.
View at: Publisher Site | Google Scholar
A. Pisciotta, G. Carnevale, S. Meloni et al., “Human Dental pulp stem cells (hDPSCs): isolation, enrichment and comparative differentiation of two sub-populations,” BMC Developmental Biology, vol. 15, no. 1, p. 14, 2015.
View at: Publisher Site | Google Scholar
P. J. Simmons and B. Torok-Storb, “Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1,” Blood, vol. 78, no. 1, pp. 55–62, 1991.
View at: Publisher Site | Google Scholar
G. Carnevale, A. Pisciotta, M. Riccio et al., “Human dental pulp stem cells expressing STRO-1, c-kit and CD34 markers in peripheral nerve regeneration,” Journal of Tissue Engineering and Regenerative Medicine, vol. 12, no. 2, pp. e774–e785, 2018.
View at: Publisher Site | Google Scholar
E. A. Jones, A. English, S. E. Kinsey et al., “Optimization of a flow cytometry-based protocol for detection and phenotypic characterization of multipotent mesenchymal stromal cells from human bone marrow,” Cytometry Part B: Clinical Cytometry, vol. 70B, no. 6, pp. 391–399, 2006.
View at: Publisher Site | Google Scholar
E. A. Jones, S. E. Kinsey, A. English et al., “Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells,” Arthritis and Rheumatism, vol. 46, no. 12, pp. 3349–3360, 2002.
View at: Publisher Site | Google Scholar
G. Nilsson, K. Forsberg-Nilsson, Z. Xiang, F. Hallböök, K. Nilsson, and D. D. Metcalfe, “Human mast cells express functional TrkA and are a source of nerve growth factor,” European Journal of Immunology, vol. 27, no. 9, pp. 2295–2301, 1997.
View at: Publisher Site | Google Scholar
C. M. Baum, I. L. Weissman, A. S. Tsukamoto, A. M. Buckle, and B. Peault, “Isolation of a candidate human hematopoietic stem-cell population,” Proceedings of the National Academy of Sciences, vol. 89, no. 7, pp. 2804–2808, 1992.
View at: Publisher Site | Google Scholar
T. Yasui, Y. Mabuchi, H. Toriumi et al., “Purified Human Dental Pulp Stem Cells Promote Osteogenic Regeneration,” Journal of Dental Research, vol. 95, no. 2, pp. 206–214, 2016.
View at: Publisher Site | Google Scholar
M. J. Tomlinson, C. Dennis, X. B. Yang, and J. Kirkham, “Tissue non-specific alkaline phosphatase production by human dental pulp stromal cells is enhanced by high density cell culture,” Cell and Tissue Research, vol. 361, no. 2, pp. 529–540, 2015.
View at: Publisher Site | Google Scholar
R. Alvarez, H.-L. Lee, C. Hong, and C.-Y. Wang, “Single CD271 marker isolates mesenchymal stem cells from human dental pulp,” International Journal of Oral Science, vol. 7, no. 4, pp. 205–212, 2015.
View at: Publisher Site | Google Scholar
A. Alraies, N. Y. A. Alaidaroos, R. J. Waddington, R. Moseley, and A. J. Sloan, “Variation in human dental pulp stem cell ageing profiles reflect contrasting proliferative and regenerative capabilities,” BMC Cell Biology, vol. 18, no. 1, p. 12, 2017.
View at: Publisher Site | Google Scholar
I. Kerkis, A. Kerkis, D. Dozortsev et al., “Isolation and characterization of a population of immature dental pulp stem cells expressing OCT-4 and other embryonic stem cell markers,” Cells, Tissues, Organs, vol. 184, no. 3-4, pp. 105–116, 2006.
View at: Publisher Site | Google Scholar
M. Miura, S. Gronthos, M. Zhao et al., “SHED: stem cells from human exfoliated deciduous teeth,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 10, pp. 5807–5812, 2003.
View at: Publisher Site | Google Scholar
A. Pivoriūnas, A. Surovas, V. Borutinskaitė et al., “Proteomic Analysis of Stromal Cells Derived from the Dental Pulp of Human Exfoliated Deciduous Teeth,” Stem Cells and Development, vol. 19, no. 7, pp. 1081–1093, 2010.
View at: Publisher Site | Google Scholar
M. Zainuri, R. R. Putri, and E. W. Bachtiar, “Establishing methods for isolation of stem cells from human exfoliated deciduous from carious deciduous teeth,” Interventional Medicine and Applied Science, vol. 10, no. 1, pp. 33–37, 2018.
View at: Publisher Site | Google Scholar
P. Ercal, G. G. Pekozer, and G. T. Kose, “Dental stem cells in bone tissue engineering: current overview and challenges,” Advances in Experimental Medicine and Biology, vol. 1107, pp. 113–127, 2018.
View at: Publisher Site | Google Scholar
R. Feng and C. Lengner, “Application of stem cell technology in dental regenerative medicine,” Advances in Wound Care, vol. 2, no. 6, pp. 296–305, 2013.
View at: Publisher Site | Google Scholar
C. Gorin, G. Y. Rochefort, R. Bascetin et al., “Priming dental pulp stem cells with fibroblast growth factor-2 increases angiogenesis of implanted tissue-engineered constructs through hepatocyte growth factor and vascular endothelial growth factor secretion,” Stem Cells Translational Medicine, vol. 5, no. 3, pp. 392–404, 2016.
View at: Publisher Site | Google Scholar
S. Ohkoshi, H. Hirono, T. Nakahara, and H. Ishikawa, “Dental pulp cell bank as a possible future source of individual hepatocytes,” World Journal of Hepatology, vol. 10, no. 10, pp. 702–707, 2018.
View at: Publisher Site | Google Scholar
V. Rosa, N. Dubey, I. Islam, K.-S. Min, and J. E. Nör, “Pluripotency of Stem Cells from Human Exfoliated Deciduous Teeth for Tissue Engineering,” Stem Cells International, vol. 2016, Article ID 5957806, 6 pages, 2016.
View at: Publisher Site | Google Scholar
G. Alessandri, S. Pagano, A. Bez et al., “Isolation and culture of human muscle-derived stem cells able to differentiate into myogenic and neurogenic cell lineages,” The Lancet, vol. 364, no. 9448, pp. 1872–1883, 2004.
View at: Publisher Site | Google Scholar
S. K. Cho, A. Bourdeau, M. Letarte, and J. C. Zúñiga-Pflücker, “Expression and function of CD105 during the onset of hematopoiesis from Flk1(+) precursors,” Blood, vol. 98, no. 13, pp. 3635–3642, 2001.
View at: Publisher Site | Google Scholar
A. Kasprzak and A. Adamek, “Role of endoglin (CD105) in the progression of hepatocellular carcinoma and anti-angiogenic therapy,” International Journal of Molecular Sciences, vol. 19, no. 12, p. 3887, 2018.
View at: Publisher Site | Google Scholar
M. Kato, V. R. Placencio-Hickok, A. Madhav et al., “Heterogeneous cancer-associated fibroblast population potentiates neuroendocrine differentiation and castrate resistance in a CD105-dependent manner,” Oncogene, vol. 38, no. 5, pp. 716–730, 2019.
View at: Publisher Site | Google Scholar
A. Madhav, A. Andres, F. Duong et al., “Antagonizing CD105 enhances radiation sensitivity in prostate cancer,” Oncogene, vol. 37, no. 32, pp. 4385–4397, 2018.
View at: Publisher Site | Google Scholar
L. Ruiz-Llorente, E. Chiapparino, S. Plumitallo et al., “Characterization of a mutation in the zona pellucida module of endoglin that causes hereditary hemorrhagic telangiectasia,” Gene, vol. 696, pp. 33–39, 2019.
View at: Publisher Site | Google Scholar
F. A. A. Ishiy, R. D. Fanganiello, G. S. Kobayashi, E. Kague, P. S. Kuriki, and M. R. Passos-Bueno, “CD105 is regulated by hsa-miR-1287 and its expression is inversely correlated with osteopotential in SHED,” Bone, vol. 106, pp. 112–120, 2018.
View at: Publisher Site | Google Scholar
W. K. Aicher, H.-J. Bühring, M. Hart, B. Rolauffs, A. Badke, and G. Klein, “Regeneration of cartilage and bone by defined subsets of mesenchymal stromal cells--Potential and pitfalls,” Advanced Drug Delivery Reviews, vol. 63, no. 4-5, pp. 342–351, 2011.
View at: Publisher Site | Google Scholar
A. Tormin, O. Li, J. C. Brune et al., “CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization,” Blood, vol. 117, no. 19, pp. 5067–5077, 2011.
View at: Publisher Site | Google Scholar
C. Y. Huang and G. J. Wu, “METCAM/MUC18 promoted tumorigenesis of human breast cancer SK-BR-3 cells in a dosage-specific manner,” Taiwanese Journal of Obstetrics & Gynecology, vol. 55, no. 2, pp. 202–212, 2016.
View at: Publisher Site | Google Scholar
T. Ito, N. Tamura, S. Okuda et al., “Elevated serum levels of soluble CD146 in patients with systemic sclerosis,” Clinical Rheumatology, vol. 36, no. 1, pp. 119–124, 2017.
View at: Publisher Site | Google Scholar
D. Liu, L. Du, D. Chen et al., “Reduced CD146 expression promotes tumorigenesis and cancer stemness in colorectal cancer through activating Wnt/β-catenin signaling,” Oncotarget, vol. 7, no. 26, pp. 40704–40718, 2016.
View at: Publisher Site | Google Scholar
X. T. Wang, N. Q. Rao, T. J. Fang, Y. M. Zhao, and L. H. Ge, “Comparison of the properties of CD146 positive and CD146 negative subpopulations of stem cells from human exfoliated deciduous teeth,” Beijing Da Xue Xue Bao. Yi Xue Ban= Journal of Peking University. Health Sciences, vol. 50, no. 2, pp. 284–292, 2018.
View at: Google Scholar
A. Bakopoulou, G. Leyhausen, J. Volk, P. Koidis, and W. Geurtsen, “Effects of resinous monomers on the odontogenic differentiation and mineralization potential of highly proliferative and clonogenic cultured apical papilla stem cells,” Dental Materials, vol. 28, no. 3, pp. 327–339, 2012.
View at: Publisher Site | Google Scholar
W. Sonoyama, Y. Liu, D. Fang et al., “Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine,” PLoS One, vol. 1, no. 1, article e79, 2006.
View at: Publisher Site | Google Scholar
J. Kang, W. Fan, Q. Deng, H. He, and F. Huang, “Stem Cells from the Apical Papilla: A Promising Source for Stem Cell-Based Therapy,” BioMed Research International, vol. 2019, Article ID 6104738, 8 pages, 2019.
View at: Publisher Site | Google Scholar
A. Choo, A. S. Ngo, V. Ding, S. Oh, and L. S. Kiang, “Autogeneic feeders for the culture of undifferentiated human embryonic stem cells in feeder and feeder-free conditions,” Methods in Cell Biology, vol. 86, pp. 15–28, 2008.
View at: Publisher Site | Google Scholar
V. Chrepa, B. Pitcher, M. A. Henry, and A. Diogenes, “Survival of the apical papilla and its resident stem cells in a case of advanced pulpal necrosis and apical periodontitis,” Journal of Endodontia, vol. 43, no. 4, pp. 561–567, 2017.
View at: Publisher Site | Google Scholar
P. Aguilar and V. Lertchirakarn, “Comparison of stem cell behaviors between indigenous high and low-CD24 percentage expressing cells of stem cells from apical papilla (SCAPs),” Tissue & Cell, vol. 48, no. 5, pp. 397–406, 2016.
View at: Publisher Site | Google Scholar
G. T.-J. Huang, W. Sonoyama, Y. Liu, H. Liu, S. Wang, and S. Shi, “The Hidden Treasure in Apical Papilla: The Potential Role in Pulp/Dentin Regeneration and BioRoot Engineering,” Journal of Endodontia, vol. 34, no. 6, pp. 645–651, 2008.
View at: Publisher Site | Google Scholar
A. Bakopoulou, A. Kritis, D. Andreadis et al., “Angiogenic potential and secretome of human apical papilla mesenchymal stem cells in various stress microenvironments,” Stem Cells and Development, vol. 24, no. 21, pp. 2496–2512, 2015.
View at: Publisher Site | Google Scholar
A. Bakopoulou, G. Leyhausen, J. Volk, P. Koidis, and W. Geurtsen, “Comparative characterization of STRO-1neg/CD146pos and STRO-1pos/CD146pos apical papilla stem cells enriched with flow cytometry,” Archives of Oral Biology, vol. 58, no. 10, pp. 1556–1568, 2013.
View at: Publisher Site | Google Scholar
B. M. Seo, M. Miura, S. Gronthos et al., “Investigation of multipotent postnatal stem cells from human periodontal ligament,” Lancet, vol. 364, no. 9429, pp. 149–155, 2004.
View at: Publisher Site | Google Scholar
D. Foudah, M. Monfrini, E. Donzelli et al., “Expression of neural markers by undifferentiated mesenchymal-like stem cells from different sources,” Journal of Immunology Research, vol. 2014, Article ID 987678, 16 pages, 2014.
View at: Publisher Site | Google Scholar
B. Lindroos, K. Mäenpää, T. Ylikomi, H. Oja, R. Suuronen, and S. Miettinen, “Characterisation of human dental stem cells and buccal mucosa fibroblasts,” Biochemical and Biophysical Research Communications, vol. 368, no. 2, pp. 329–335, 2008.
View at: Publisher Site | Google Scholar
D. Ponnaiyan, K. M. Bhat, and G. S. Bhat, “Comparison of immuno-phenotypes of stem cells from human dental pulp and periodontal ligament,” International Journal of Immunopathology and Pharmacology, vol. 25, no. 1, pp. 127–134, 2012.
View at: Publisher Site | Google Scholar
E. Prateeptongkum, C. Klingelhöffer, S. Müller, T. Ettl, and C. Morsczeck, “Characterization of progenitor cells and stem cells from the periodontal ligament tissue derived from a single person,” Journal of Periodontal Research, vol. 51, no. 2, pp. 265–272, 2016.
View at: Publisher Site | Google Scholar
A. Szepesi, Z. Matula, A. Szigeti et al., “ABCG2 is a selectable marker for enhanced multilineage differentiation potential in periodontal ligament stem cells,” Stem Cells and Development, vol. 24, no. 2, pp. 244–252, 2015.
View at: Publisher Site | Google Scholar
H. Huang, R. Yang, and Y. H. Zhou, “Mechanobiology of periodontal ligament stem cells in orthodontic tooth movement,” Stem Cells International, vol. 2018, Article ID 6531216, 7 pages, 2018.
View at: Publisher Site | Google Scholar
K. Iwasaki, K. Washio, W. Meinzer, Y. Tsumanuma, K. Yano, and I. Ishikawa, “Application of cell-sheet engineering for new formation of cementum around dental implants,” Heliyon, vol. 5, no. 6, article e01991, 2019.
View at: Publisher Site | Google Scholar
H. Chopra, C. Liao, C. F. Zhang, and E. H. N. Pow, “Lapine periodontal ligament stem cells for musculoskeletal research in preclinical animal trials,” Journal of Translational Medicine, vol. 16, no. 1, p. 174, 2018.
View at: Publisher Site | Google Scholar
M. Alvarez-Viejo, Y. Menendez-Menendez, and J. Otero-Hernandez, “CD271 as a marker to identify mesenchymal stem cells from diverse sources before culture,” World Journal of Stem Cells, vol. 7, no. 2, pp. 470–476, 2015.
View at: Publisher Site | Google Scholar
C. A. Nosrat, K. Fried, S. Lindskog, and L. Olson, “Cellular expression of neurotrophin mRNAs during tooth development,” Cell and Tissue Research, vol. 290, no. 3, pp. 569–580, 1997.
View at: Publisher Site | Google Scholar
R. Alvarez, H. L. Lee, C. Y. Wang, and C. Hong, “Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers,” International Journal of Oral Science, vol. 7, no. 4, pp. 213–219, 2015.
View at: Publisher Site | Google Scholar
C. Morsczeck, W. Götz, J. Schierholz et al., “Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth,” Matrix Biology, vol. 24, no. 2, pp. 155–165, 2005.
View at: Publisher Site | Google Scholar
F. Angiero, C. Rossi, A. Ferri et al., “Stromal phenotype of dental follicle stem cells,” Frontiers in Bioscience, vol. 4, pp. 1009–1014, 2012.
View at: Google Scholar
R. L. Lima, R. C. Holanda-Afonso, V. Moura-Neto, A. M. Bolognese, M. F. DosSantos, and M. M. Souza, “Human dental follicle cells express embryonic, mesenchymal and neural stem cells markers,” Archives of Oral Biology, vol. 73, pp. 121–128, 2017.
View at: Publisher Site | Google Scholar
B. W. Park, S. J. Jang, J. H. Byun et al., “Cryopreservation of human dental follicle tissue for use as a resource of autologous mesenchymal stem cells,” Journal of Tissue Engineering and Regenerative Medicine, vol. 11, no. 2, pp. 489–500, 2017.
View at: Publisher Site | Google Scholar
B. C. Kim, H. Bae, I. K. Kwon et al., “Osteoblastic/cementoblastic and neural differentiation of dental stem cells and their applications to tissue engineering and regenerative medicine,” Tissue Engineering Part B: ReviewsTissue Engineering. Part B, Reviews, vol. 18, no. 3, pp. 235–244, 2012.
View at: Publisher Site | Google Scholar
D. Sybil, V. Jain, S. Mohanty, and S. A. Husain, “Oral stem cells in intraoral bone formation,” Journal of Oral Biosciences, vol. 62, no. 1, pp. 36–43, 2020.
View at: Publisher Site | Google Scholar
C. L. Holness and D. L. Simmons, “Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins,” Blood, vol. 81, no. 6, pp. 1607–1613, 1993.
View at: Publisher Site | Google Scholar
A. C. Didilescu, F. Pop, and M. C. Rusu, “c-Kit positive cells and networks in tooth germs of human midterm fetuses,” Annals of Anatomy, vol. 195, no. 6, pp. 581–585, 2013.
View at: Publisher Site | Google Scholar
M. C. Rusu, A. Rascu, and M. D. Stoenescu, “Endothelial expression of c-kit and CD68 in dental follicles of human impacted third molars,” Folia Morphologica, vol. 77, no. 3, pp. 485–488, 2018.
View at: Google Scholar
S. Ge, K. M. Mrozik, D. Menicanin, S. Gronthos, and P. M. Bartold, “Isolation and characterization of mesenchymal stem cell-like cells from healthy and inflamed gingival tissue: potential use for clinical therapy,” Regenerative Medicine, vol. 7, no. 6, pp. 819–832, 2012.
View at: Publisher Site | Google Scholar
M. E. Grawish, “Gingival-derived mesenchymal stem cells: an endless resource for regenerative dentistry,” World Journal of Stem Cells, vol. 10, no. 9, pp. 116–118, 2018.
View at: Publisher Site | Google Scholar
S. H. Jin, J. E. Lee, J. H. Yun, I. Kim, Y. Ko, and J. B. Park, “Isolation and characterization of human mesenchymal stem cells from gingival connective tissue,” Journal of Periodontal Research, vol. 50, no. 4, pp. 461–467, 2015.
View at: Publisher Site | Google Scholar
S. I. Lee, Y. Ko, and J. B. Park, “Evaluation of the maintenance of stemness, viability, and differentiation potential of gingiva-derived stem-cell spheroids,” Experimental and Therapeutic Medicine, vol. 13, no. 5, pp. 1757–1764, 2017.
View at: Publisher Site | Google Scholar
J. Li, S. Q. Xu, Y. M. Zhao, S. Yu, L. H. Ge, and B. H. Xu, “Comparison of the biological characteristics of human mesenchymal stem cells derived from exfoliated deciduous teeth, bone marrow, gingival tissue, and umbilical cord,” Molecular Medicine Reports, vol. 18, no. 6, pp. 4969–4977, 2018.
View at: Publisher Site | Google Scholar
Q. Zhang, S. Shi, Y. Liu et al., “Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis,” Journal of Immunology, vol. 183, no. 12, pp. 7787–7798, 2009.
View at: Publisher Site | Google Scholar
N. Zhao, Z. Wu, L. Qin, Z. Guo, and D. Li, “Characteristics and tissue regeneration properties of gingiva-derived mesenchymal stem cells,” Critical Reviews in Eukaryotic Gene Expression, vol. 25, no. 2, pp. 135–144, 2015.
View at: Publisher Site | Google Scholar
C. Sattler, M. Steinsdoerfer, M. Offers et al., “Inhibition of T-cell proliferation by murine multipotent mesenchymal stromal cells is mediated by CD39 expression and adenosine generation,” Cell Transplantation, vol. 20, no. 8, pp. 1221–1230, 2011.
View at: Publisher Site | Google Scholar
A. Thiolat, L. Semerano, Y. M. Pers et al., “Interleukin-6 receptor blockade enhances CD39+ regulatory T cell development in rheumatoid arthritis and in experimental arthritis,” Arthritis & Rhematology, vol. 66, no. 2, pp. 273–283, 2014.
View at: Publisher Site | Google Scholar
Y. Luo, W. Wu, J. Gu et al., “Human gingival tissue-derived MSC suppress osteoclastogenesis and bone erosion via CD39-adenosine signal pathway in autoimmune arthritis,” eBioMedicine, vol. 43, pp. 620–631, 2019.
View at: Publisher Site | Google Scholar
F. Huang, M. Chen, W. Chen et al., “Human gingiva-derived mesenchymal stem cells inhibit xeno-graft-versus-host disease via CD39-CD73-adenosine and IDO signals,” Frontiers in Immunology, vol. 8, p. 68, 2017.
View at: Publisher Site | Google Scholar
X. Ni, Y. Xia, S. Zhou et al., “Reduction in murine acute GVHD severity by human gingival tissue-derived mesenchymal stem cells via the CD39 pathways,” Cell Death & Disease, vol. 10, no. 1, p. 13, 2019.
View at: Publisher Site | Google Scholar
E. Ikeda, K. Yagi, M. Kojima et al., “Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease,” Differentiation, vol. 76, no. 5, pp. 495–505, 2008.
View at: Publisher Site | Google Scholar
M. E. Yalvac, M. Ramazanoglu, A. A. Rizvanov et al., “Isolation and characterization of stem cells derived from human third molar tooth germs of young adults: implications in neo-vascularization, osteo-, adipo- and neurogenesis,” The Pharmacogenomics Journal, vol. 10, no. 2, pp. 105–113, 2010.
View at: Publisher Site | Google Scholar
M. E. Yalvac, M. Ramazanoglu, M. Tekguc et al., “Human tooth germ stem cells preserve neuro-protective effects after long-term cryo-preservation,” Current Neurovascular Research, vol. 7, no. 1, pp. 49–58, 2010.
View at: Publisher Site | Google Scholar
S. Aydin and F. Sahin, “Stem cells derived from dental tissues,” Advances in Experimental Medicine and Biology, vol. 1144, pp. 123–132, 2019.
View at: Publisher Site | Google Scholar
P. Ercal, G. G. Pekozer, O. Z. Gumru, G. T. Kose, and M. Ramazanoglu, “Influence of STRO-1 selection on osteogenic potential of human tooth germ derived mesenchymal stem cells,” Archives of Oral Biology, vol. 82, pp. 293–301, 2017.
View at: Publisher Site | Google Scholar
G. Gurel Pekozer, M. Ramazanoglu, K. A. Schlegel, F. N. Kok, and G. Torun Kose, “Role of STRO-1 sorting of porcine dental germ stem cells in dental stem cell-mediated bone tissue engineering,” Artificial Cells, Nanomedicine, and Biotechnology, vol. 46, no. 3, pp. 607–618, 2018.
View at: Publisher Site | Google Scholar
S. Mason, S. A. Tarle, W. Osibin, Y. Kinfu, and D. Kaigler, “Standardization and safety of alveolar bone-derived stem cell isolation,” Journal of Dental Research, vol. 93, no. 1, pp. 55–61, 2014.
View at: Publisher Site | Google Scholar
T. Matsubara, K. Suardita, M. Ishii et al., “Alveolar bone marrow as a cell source for regenerative medicine: differences between alveolar and iliac bone marrow stromal cells,” Journal of Bone and Mineral Research, vol. 20, no. 3, pp. 399–409, 2005.
View at: Publisher Site | Google Scholar
J. C. Park, J. C. Kim, Y. T. Kim et al., “Acquisition of human alveolar bone-derived stromal cells using minimally irrigated implant osteotomy: in vitro and in vivo evaluations,” Journal of Clinical Periodontology, vol. 39, no. 5, pp. 495–505, 2012.
View at: Publisher Site | Google Scholar
V. L. Zorin, A. A. Pulin, I. I. Eremin et al., “Myogenic potential of human alveolar mucosa derived cells,” Cell Cycle, vol. 16, no. 6, pp. 545–555, 2017.
View at: Publisher Site | Google Scholar
C. Cao, S. Tarle, and D. Kaigler, “Characterization of the immunomodulatory properties of alveolar bone-derived mesenchymal stem cells,” Stem Cell Research & Therapy, vol. 11, no. 1, p. 102, 2020.
View at: Publisher Site | Google Scholar
S. Cantore, V. Crincoli, A. Boccaccio et al., “Recent advances in endocrine, metabolic and immune disorders: mesenchymal stem cells (MSCs) and engineered scaffolds,” Endocrine, Metabolic & Immune Disorders Drug Targets, vol. 18, no. 5, pp. 466–469, 2018.
View at: Publisher Site | Google Scholar
P. Hilkens, N. Meschi, P. Lambrechts, A. Bronckaers, and I. Lambrichts, “Dental stem cells in pulp regeneration: near future or long road ahead?” Stem Cells and Development, vol. 24, no. 14, pp. 1610–1622, 2015.
View at: Publisher Site | Google Scholar
Q. Zhai, Z. Dong, W. Wang, B. Li, and Y. Jin, “Dental stem cell and dental tissue regeneration,” Frontiers in Medicine, vol. 13, no. 2, pp. 152–159, 2019.
View at: Publisher Site | Google Scholar
M. Boccellino, D. di Stasio, G. Dipalma et al., “Steroids and growth factors in oral squamous cell carcinoma: useful source of dental-derived stem cells to develop a steroidogenic model in new clinical strategies,” European Review for Medical and Pharmacological Sciences, vol. 23, no. 20, pp. 8730–8740, 2019.
View at: Publisher Site | Google Scholar
S. el Moshy, I. A. Radwan, D. Rady et al., “Dental stem cell-derived secretome/conditioned medium: the future for regenerative therapeutic applications,” Stem Cells International, vol. 2020, Article ID 7593402, 29 pages, 2020.
View at: Publisher Site | Google Scholar
D. K. Smith, M. He, C. L. Zhang, and J. C. Zheng, “The therapeutic potential of cell identity reprogramming for the treatment of aging-related neurodegenerative disorders,” Progress in Neurobiology, vol. 157, pp. 212–229, 2017.
View at: Publisher Site | Google Scholar
A. Mishra, S. Singh, V. Tiwari, Parul, and S. Shukla, “Dopamine D1 receptor activation improves adult hippocampal neurogenesis and exerts anxiolytic and antidepressant-like effect via activation of Wnt/β-catenin pathways in rat model of Parkinson's disease,” Neurochemistry International, vol. 122, pp. 170–186, 2019.
View at: Publisher Site | Google Scholar
Z. Si, X. Wang, Y. Kang et al., “Heme oxygenase 1 inhibits adult neural stem cells proliferation and survival via modulation of Wnt/β-catenin signaling,” Journal of Alzheimer's Disease, vol. 76, no. 2, pp. 623–641, 2020.
View at: Publisher Site | Google Scholar
E. Curtis, J. R. Martin, B. Gabel et al., “A first-in-human, phase I study of neural stem cell transplantation for chronic spinal cord injury,” Cell Stem Cell, vol. 22, no. 6, pp. 941–950.e6, 2018, e6.
View at: Publisher Site | Google Scholar
R. M. Martin, J. L. Fowler, M. K. Cromer et al., “Improving the safety of human pluripotent stem cell therapies using genome-edited orthogonal safeguards,” Nature Communications, vol. 11, no. 1, p. 2713, 2020.
View at: Publisher Site | Google Scholar
M. H. Sidiqi, M. A. Aljama, F. K. Buadi et al., “Stem cell transplantation for light chain amyloidosis: decreased early mortality over time,” Journal of Clinical Oncology, vol. 36, no. 13, pp. 1323–1329, 2018.
View at: Publisher Site | Google Scholar
N. Farrow, P. Cmielewski, M. Donnelley et al., “Epithelial disruption: a new paradigm enabling human airway stem cell transplantation,” Stem Cell Research & Therapy, vol. 9, no. 1, p. 153, 2018.
View at: Publisher Site | Google Scholar
N. Petinati, N. Drize, N. Sats et al., “Recovery of donor hematopoiesis after graft failure and second hematopoietic stem cell transplantation with intraosseous administration of mesenchymal stromal cells,” Stem Cells International, vol. 2018, Article ID 6495018, 7 pages, 2018.
View at: Publisher Site | Google Scholar
M. Vela, T. del Rosal, A. Pérez-Martínez et al., “Possible role of highly activated mucosal NK cells against viral respiratory infections in children undergoing haematopoietic stem cell transplantation,” Scientific Reports, vol. 9, no. 1, p. 18792, 2019.
View at: Publisher Site | Google Scholar
B. Hernández-Monjaraz, E. Santiago-Osorio, A. Monroy-García, E. Ledesma-Martínez, and V. Mendoza-Núñez, “Mesenchymal stem cells of dental origin for inducing tissue regeneration in periodontitis: a mini-review,” International Journal of Molecular Sciences, vol. 19, no. 4, p. 944, 2018.
View at: Publisher Site | Google Scholar
T. Yu and O. D. Klein, “Molecular and cellular mechanisms of tooth development, homeostasis and repair,” Development, vol. 147, no. 2, 2020.
View at: Publisher Site | Google Scholar
M. Ramamoorthi, M. Bakkar, J. Jordan, and S. D. Tran, “Osteogenic potential of dental mesenchymal stem cells in preclinical studies: a systematic review using modified ARRIVE and CONSORT guidelines,” Stem Cells International, vol. 2015, Article ID 378368, 28 pages, 2015.
View at: Publisher Site | Google Scholar
V. Taraslia, S. Lymperi, V. Pantazopoulou et al., “A high-resolution proteomic landscaping of primary human dental stem cells: identification of SHED- and PDLSC-specific biomarkers,” International Journal of Molecular Sciences, vol. 19, no. 1, p. 158, 2018.
View at: Publisher Site | Google Scholar
A. Kumar, V. Kumar, V. Rattan, V. Jha, and S. Bhattacharyya, “Secretome proteins regulate comparative osteogenic and adipogenic potential in bone marrow and dental stem cells,” Biochimie, vol. 155, pp. 129–139, 2018.
View at: Publisher Site | Google Scholar
H. Wang, J. Li, X. Zhang et al., “Priming integrin alpha 5 promotes the osteogenic differentiation of human periodontal ligament stem cells due to cytoskeleton and cell cycle changes,” Journal of Proteomics, vol. 179, pp. 122–130, 2018.
View at: Publisher Site | Google Scholar
M. K. Kolar, V. N. Itte, P. J. Kingham, L. N. Novikov, M. Wiberg, and P. Kelk, “The neurotrophic effects of different human dental mesenchymal stem cells,” Scientific Reports, vol. 7, no. 1, p. 12605, 2017.
View at: Publisher Site | Google Scholar
A. Rahmani, K. Saleki, N. Javanmehr, J. Khodaparast, P. Saadat, and H. R. Nouri, “Mesenchymal stem cell-derived extracellular vesicle-based therapies protect against coupled degeneration of the central nervous and vascular systems in stroke,” Ageing Research Reviews, vol. 62, p. 101106, 2020.
View at: Publisher Site | Google Scholar
A. Tieu, M. M. Lalu, M. Slobodian et al., “An analysis of mesenchymal stem cell-derived extracellular vesicles for preclinical use,” ACS Nano, vol. 14, no. 8, pp. 9728–9743, 2020.
View at: Publisher Site | Google Scholar
W. A. Banks, P. Sharma, K. M. Bullock, K. M. Hansen, N. Ludwig, and T. L. Whiteside, “Transport of extracellular vesicles across the blood-brain barrier: brain pharmacokinetics and effects of inflammation,” International Journal of Molecular Sciences, vol. 21, no. 12, p. 4407, 2020.
View at: Publisher Site | Google Scholar
S. L. French, K. R. Butov, I. Allaeys et al., “Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation,” Blood Advances, vol. 4, no. 13, pp. 3011–3023, 2020.
View at: Publisher Site | Google Scholar
S. Kumar, N. El-Hage, and E. Batrakova, “Extracellular vesicles in HIV, drug abuse, and drug delivery,” Journal of Neuroimmune Pharmacology, vol. 15, no. 3, pp. 387–389, 2020.
View at: Publisher Site | Google Scholar
H. Peng, W. Ji, R. Zhao et al., “Exosome: a significant nano-scale drug delivery carrier,” Journal of Materials Chemistry B, vol. 8, no. 34, pp. 7591–7608, 2020.
View at: Publisher Site | Google Scholar
S. Zhang, A. L. Thiebes, F. Kreimendahl et al., “Extracellular vesicles-loaded fibrin gel supports rapid neovascularization for dental pulp regeneration,” International Journal of Molecular Sciences, vol. 21, no. 12, p. 4226, 2020.
View at: Publisher Site | Google Scholar
H. Zhou, X. Li, Y. Yin et al., “The proangiogenic effects of extracellular vesicles secreted by dental pulp stem cells derived from periodontally compromised teeth,” Stem Cell Research & Therapy, vol. 11, no. 1, p. 110, 2020.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Tong Lei et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

1262

Downloads

1017

Citations