Cell-Based Transplantation versus Cell Homing Approaches for Pulp-Dentin Complex Regeneration
Table 1
Summary of cell-based transplantation studies for pulp-dentin complex regeneration.
Study
Study design
Outcomes
Blind; random; design
Animal model/human
Type of study
Groups
Primary outcomes
Secondary outcomes
Histology
Clinically and radiographically
Discoloration and sensibility test
Chen et al. 2015
Randomized controlled trial
Animal study; 3 dogs providing 60 root canals
Cell based
Group I: DPSC/PRF construct Group II: DPSCs only Group III: PRF granules only Group IV: blank controls without any exogenous transplanted grafts
DPSC/PRF construct led induced regeneration of dense pulp-like tissues with richly distributed blood capillaries. The deposition of regenerated dentin alongside the intracanal walls was evident.
Cai et al. 2016
Randomized controlled trial
Animal study; 6 rats, 12 incisors
Cell based
Group I: 6 untouched incisors Group II: 2 sham incisors Group III: 4 transplanted incisors
Immunohistochemistry revealed globular dentin and pulp-like tissue formation.
Jia et al. 2016
Randomized controlled trial
Animal study; 18 immature premolars from 2 dogs
Cell based
Group I: mineral trioxide aggregate Group II: absorbable gelatin sponge Group III: cDPSCs Group IV: Simvastatin group
Simvastatin stimulated cDPSC mineralization and induced DPSC pulp and dentin regeneration.
After 10 weeks, radiographic examination of pulpotomized teeth showed closure of the root apex and thickening of the root canal wall.
cDPSCs pretreated with SI, regenerated pulp that was filling most of the pulp cavity. Newly formed dentin deposits succeed to the primary dentin and odontoblasts were evident in the regenerated area. It was significantly higher than that in all other groups.
Iohara et al. 2016
Randomized controlled trial
Animal study; a total of 28 teeth from 5 dogs were randomly divided into 4 groups.
Cell based
Group I: pulpectomy only (no cells and no collagen) Group II: normal teeth Group III: transplantation of MDPSCs and 7.5 ng/mL G-CSF with an atelocollagen scaffold Group IV: collagen only
The signal intensity (SI) of MRI of the normal teeth was significantly higher than that of nonvital pulpectomized teeth and the controls of collagen transplanted teeth at 90 days. The stem cell transplanted teeth showed gradual decrease in the SI until 180 days which was similar to the normal teeth and significantly higher than that in the teeth transplanted with collagen alone without the stem cells.
One day after transplantation of collagen alone or MDPSCs and G-CSF with collagen, the root canal was filled with collagen like-fibers. Ninety days after the transplantation of MDPSCs and G-CSF with collagen, most of the root canal was filled with pulp-like tissue in which well-developed vasculature and dentin were formed along the dentinal wall. On day 180, the root canal was completely filled with pulp-like tissue and secondary dentin was formed in the apical part and along the dentinal wall.
Bakhtiar et al. 2017
Randomized controlled trial
Animal study; 32 premolars of 5 dogs
Cell based
Group A: MTA Group B: TDM Group C: TCP Group D: TDM scaffold impregnated with DPSCs+TDM Group E: TCP scaffold impregnated with DPSCs+TCP
The negative control group showed severe inflammation and granulation tissue formation. The positive control group was characterized by intact periodontal tissues and no inflammation.
Dentin bridge formation was absent in specimens of all groups. The SC+TDM group was associated with significantly more bone formation than other groups. Cementum was formed with a cellular and continuous pattern in all specimens.
Ito et al. 2017
Randomized controlled trial
Animal study; 48 female Wistar rats
Cell based
Group 1: RBMMSC/PLLA/Matrigel constructs Group 2: Matrigel constructs without RBMMSC Constructs were implanted into the cavity for 3, 7, or 14 days ( in each group).
Immunohistochemistry revealed that nestin-expressing odontoblast-like cells beneath the dentin at the border of implanted area increased until 14 days.
Considering RBMMSC constructs at 3 days, cells were located mainly along the implanted scaffolds. At 7 days, pulp tissue regeneration was created in almost the entire implanted region. At 14 days, pulp tissue regeneration continued throughout the implanted region.
Mangione et al. 2017
Randomized controlled study, split-mouth model
Animal study; 3 minipigs, of total 48 teeth
Cell based
Group 1: pDPCs were implanted in the left maxillary and mandibular teeth. Group 2: no pDPC scaffold was implanted in teeth of the right side.
Micro-CT examination of the treated teeth showed the formation of a reparative mineralized bridge in the remaining pulp of both groups. External root resorption was evident in all teeth.
With pDPSCs, reparative dentin bridge presented many abundant and joined nonmineralized areas.
Sueyama et al. 2017
Randomized controlled trial
Animal study; 40 female rats
Cell based
Group 1: PLLA implanted scaffolds with MSCs and Ecs Group 2: implanted scaffolds with MSCs Group 3: implanted acellular scaffolds Group 4: pulpotomy cavities were sealed with MTA only. Group 5: no pulpotomy (used as the normal control)
14 days after implantation; MSCs associating Ecs accelerated the pulp tissue regeneration and enhanced dentin bridge formation.
Teeth with MSC/EC constructs showed pulp healing and complete dentin bridge formation, but MSCs alone showed incomplete, thinner dentin bridges. Teeth implanted with acellular scaffolds were of poor tissue regeneration in the implanted area and incomplete hard tissue formation. Teeth subjected to pulpotomy without implantation did not show pulp tissue regeneration.
El Ashiry et al. 2018
Randomized controlled trial, split-mouth design
Animal study; 12 dogs, 36 teeth
Cell based
Group A: tooth transplanted with a construct of autologous dental pulp stem cells with growth factors seeded in a chitosan hydrogel scaffold Group B: tooth received only growth factors with scaffold.
DPSC constructs resulted in complete root maturation., radicular thickening, root lengthening, and apical closure.
DPSC constructs showed regeneration of pulp-dentin-like tissue filling the emptied canals. The vascularized pulp-like tissue resembled the natural pulp. On the contrary, in the other group, no soft tissues were observed.
Cordero et al. 2020
Case report
Human mature molar with accidental root perforation
Cell based
Radiographic and cone-beam computed tomographic images indicated remission of the apical lesion. Clinically, normal responses to percussion and palpation tests
Tooth was responsive to the electric pulp test, and the vitality test indicated low blood perfusion units.
Iohara et al. 2020
Randomized controlled trial
Animal study; aged dogs
Cell based
Group I: no treatment Group II: nanobubble treatment Group III: 0.05% trypsin for 10 min Group IV: 0.5% trypsin for 10 min Group V: 0.05% trypsin for 30 min Group VI: 0.05% trypsin for 10 min with nanobubbles
The amount of pulp-like regenerated tissues was three-times higher with 0.05 and 0.5% trypsin pretreatment for 10 min than that in the no treatment group. Moreover, the trypsin pretreatment induced higher pulp tissue vascularization compared with no pretreatment.
