Review Article

Therapeutic Potential of Stem Cells in Follicle Regeneration

Table 2

Researches on the use of stem cells in the regeneration of hair follicles.

AuthorsResearch objectIndicationMethods of obtainingResultsComments

Usage of hair follicle stem cell
Agabalyan et al., 2016 [56]Sprague Dawley rats/nude miceNude mice genetically mutatedBioreactors and static cell cultures with bFGF, PGFInducing de novo HF formation, reconstituting the DP and connective tissue sheathCompared with static culture, stirred suspension bioreactors were significantly reduced, but they can generate larger numbers of autologous DSCs, maintaining their regenerative function
Nilforoushzadeh et al., 2016 [59]Human/miceNude mice genetically mutatedHuman scalp biopsy, isolation of only papilla cells which were cultured and injected into nude miceEvidence of hair growth in mice received epithelial and DP cellsThe combination of human cultured DP and epithelial cells could induce HF in nude mice
Elmaadawi et al., 2018 [21]HumanAlopecia areata and androgenetic alopeciaAutologous bone marrow-derived mononuclear cells compared to follicular stems cells (skin punch biopsy from unaffected areas)Good clinical improvement in both diseasesNonstatistically significant difference between the source of cells
Gentile et al., 2017 [5]HumanAndrogenetic alopeciaBiopsies were collected and disaggregated by Rigeneracons without culture condition, then injected to the frontal scalpA 29% ± 5% increase in hair density for the treated area and less than 1% in hair density for the placebo areaNo culture required, quick time of surgery (about 60 min)
Kalabusheva et al., 2017 [120]HumanIn vitro studyHuman DP cells and skin epidermal keratinocytes in a hanging drop culture to develop an artificial HF germAggrecan, biglycan, fibronectin, and hyaluronic acid significantly stimulated cell proliferation in a DP cell monolayer culture without any effect on DP cell identityMost of the ECM compounds prevented the formation of cell aggregates while hyaluronic acid promoted the formation of larger organoids
Hoffman et al., 2018 [121]Human/miceIn vitro studyHair follicle-associated-pluripotent stem cells from human scalp skin and transgenic mice with nestin-driven GFPIntensive hair growth was observed in the pieces of shaved mouse skin histocultured on GelfoamModel for chemotherapy-induced alopecia (observing a doxorubicin effect)

Usage of adipose-derived stem cells
Park et al., 2010 [74]Human/miceC (3)H/NeH nude miceADSCs in a conditioned medium injected subcutaneously induced the anagen phase from telogen and increased hair regeneration in nude miceADSCs in a conditioned medium increased the proliferation of human DP and human epithelial keratinocytes; the effect of hypoxia on ADSC function increased hair regrowthThe secretion of IGFBP, M-CSF receptor, PGF, and VEGF was significantly increased by hypoxia, while the secretion of EGF production was decreased
Zanzoterra et al., 2014 [78]HumanAndrogenic alopeciaInjection of ADSCs and growth factorsAfter 2 weeks, the healing of microwounds was complete and HF continued growingRigenera system for the automated mechanical disaggregation of cell population
Sabapathy et al., 2016 [82]RatsIn vitro studyADSCs isolated from rats were cocultured with DP spheresA core-shell structure, outer ASCs shell, and an inner DP core exhibited superior potential to HF formation compared to a mixed sphere of ADSCs with DP cellsPPARα signal in ADSCs can induce the hair formation
Yang et al., 2016 [69]Human/miceC57BL/6 nude miceCocultured human ADSCs with LL-37 was topically applied daily on the mouse skinThe conditioned medium of ADSCs preactivated with LL-37 strongly promoted hair growth in vivoLL-37 treatment significantly increased EGR-1 expression
Anderi et al., 2018 [122]HumanAlopecia areataLipoaspiration, autologous ADSCs were injected into the scalp of the patient (4–4.7 × 106 cells)Increased hair growth and decreased pull test, 3 and 6 months after ADSCsSignificant variation was observed between men and women only for hair diameter, no differences with age

Usage of Wharton’s jelly and embryo stem cells
Yoo et al., 2010 [88]HumanIn vitro studyCultivated umbilical stem cells with EGF, HGF, and NGFFormation of aggregates similar to native DP in special media and reconstructed dermal papilla-like tissuesHGF is necessary in the differentiation step
Yoo et al., 2010 [89]Human/miceAthymic nude mice genetically mutatedIsolated and cultivated stem cells from bone marrow and umbilical cord, after obtaining a DP-forming medium, injected in skin of nude miceEffect of inducing new HF in mice within 45 days
Wu et al., 2012 [90]Human embryo MSCs/miceNude mice genetically mutatedThree cultures: DP cells cocultured with hMSCs; DP cells cocultured with fibroblasts; hMSCs cultured single, next injected into skin of miceIn fibroblast injection to mice, no HF was foundThe expression in vivo of HLA-I was confined to DP of the newly grown hair, and the survival time of hMSCs in mice is 1 month

ADSCs: adipose-derived stem cells; DP: dermal papilla; DSCs: dermal stem cells; EGF: epidermal growth factor; bFGF: basic fibroblast growth factor; HF: hair follicle; HGF: hepatocyte growth factor; HLA-I: human leucocyte antigen class I; hMSCs: human mesenchymal stem cells; IGFBP: insulin-like growth factor-binding protein; M-CSF: macrophage colony-stimulating factor; NGF: nerve growth factor; PGF: platelet-derived growth factor; VEGF: vascular endothelial growth factor.