Table 2.
Researches on the use of stem cells in the regeneration of hair follicles.
| Authors | Research object | Indication | Methods of obtaining | Results | Comments |
|---|---|---|---|---|---|
| Usage of hair follicle stem cell | |||||
| Agabalyan et al., 2016 [56] | Sprague Dawley rats/nude mice | Nude mice genetically mutated | Bioreactors and static cell cultures with bFGF, PGF | Inducing de novo HF formation, reconstituting the DP and connective tissue sheath | Compared 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/mice | Nude mice genetically mutated | Human scalp biopsy, isolation of only papilla cells which were cultured and injected into nude mice | Evidence of hair growth in mice received epithelial and DP cells | The combination of human cultured DP and epithelial cells could induce HF in nude mice |
| Elmaadawi et al., 2018 [21] | Human | Alopecia areata and androgenetic alopecia | Autologous bone marrow-derived mononuclear cells compared to follicular stems cells (skin punch biopsy from unaffected areas) | Good clinical improvement in both diseases | Nonstatistically significant difference between the source of cells |
| Gentile et al., 2017 [5] | Human | Androgenetic alopecia | Biopsies were collected and disaggregated by Rigeneracons without culture condition, then injected to the frontal scalp | A 29% ± 5% increase in hair density for the treated area and less than 1% in hair density for the placebo area | No culture required, quick time of surgery (about 60 min) |
| Kalabusheva et al., 2017 [120] | Human | In vitro study | Human DP cells and skin epidermal keratinocytes in a hanging drop culture to develop an artificial HF germ | Aggrecan, biglycan, fibronectin, and hyaluronic acid significantly stimulated cell proliferation in a DP cell monolayer culture without any effect on DP cell identity | Most 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/mice | In vitro study | Hair follicle-associated-pluripotent stem cells from human scalp skin and transgenic mice with nestin-driven GFP | Intensive hair growth was observed in the pieces of shaved mouse skin histocultured on Gelfoam | Model for chemotherapy-induced alopecia (observing a doxorubicin effect) |
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| Usage of adipose-derived stem cells | |||||
| Park et al., 2010 [74] | Human/mice | C (3)H/NeH nude mice | ADSCs in a conditioned medium injected subcutaneously induced the anagen phase from telogen and increased hair regeneration in nude mice | ADSCs in a conditioned medium increased the proliferation of human DP and human epithelial keratinocytes; the effect of hypoxia on ADSC function increased hair regrowth | The 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] | Human | Androgenic alopecia | Injection of ADSCs and growth factors | After 2 weeks, the healing of microwounds was complete and HF continued growing | Rigenera system for the automated mechanical disaggregation of cell population |
| Sabapathy et al., 2016 [82] | Rats | In vitro study | ADSCs isolated from rats were cocultured with DP spheres | A 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 cells | PPARα signal in ADSCs can induce the hair formation |
| Yang et al., 2016 [69] | Human/mice | C57BL/6 nude mice | Cocultured human ADSCs with LL-37 was topically applied daily on the mouse skin | The conditioned medium of ADSCs preactivated with LL-37 strongly promoted hair growth in vivo | LL-37 treatment significantly increased EGR-1 expression |
| Anderi et al., 2018 [122] | Human | Alopecia areata | Lipoaspiration, 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 ADSCs | Significant variation was observed between men and women only for hair diameter, no differences with age |
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| Usage of Wharton's jelly and embryo stem cells | |||||
| Yoo et al., 2010 [88] | Human | In vitro study | Cultivated umbilical stem cells with EGF, HGF, and NGF | Formation of aggregates similar to native DP in special media and reconstructed dermal papilla-like tissues | HGF is necessary in the differentiation step |
| Yoo et al., 2010 [89] | Human/mice | Athymic nude mice genetically mutated | Isolated and cultivated stem cells from bone marrow and umbilical cord, after obtaining a DP-forming medium, injected in skin of nude mice | Effect of inducing new HF in mice within 45 days | |
| Wu et al., 2012 [90] | Human embryo MSCs/mice | Nude mice genetically mutated | Three cultures: DP cells cocultured with hMSCs; DP cells cocultured with fibroblasts; hMSCs cultured single, next injected into skin of mice | In fibroblast injection to mice, no HF was found | The 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.