TABLE 7.
Studies regarding mesenchymal stromal cell-conditioned medium for hair restoration in animal models.
| MSC source | Method of tissue extraction | MSC characterization | MSC treatment | Model | Groups of treatments and via of administration | Follow-up (days) | Assessment | Main outcome | Other outcomes | |
| Xiao et al., 2020 | Human adipose tissue | Fat grafting | IF (alkaline phosphatase+ and β-catenin+) | MSCs of passage 3 were used. CM from MSCs and from ECM/SVF-gel was collected | Murine. Back hair shaved with clippers and then completely removed using hair remover cream | Injected subcutaneously in the dorsal skin once per week - PBS (control) - ECM/ADSVC-CM - ADSVC-CM (n = 10/group) |
21 | Macroscopic appearance (skin darkening, hair growth score, gross observation of the inner skin of the hair-regrowth), IHC (CD31), WB | Both CMs enhanced hair growth. CM from ECM/SVF had a stronger ability to stimulate hair growth. 95–100% hair regeneration to full length was observed in the ECM/SVF group and 70–75% in the ADSVC-CM group | Both CM promoted dermal papilla cells and bulge cell proliferation, neovascularization, and anagen induction. Growth factor levels (VEGF, bFGF, PDGF, KGF) increased in CM-treated mice, even more than in ECM/ADSVC-CM group |
| Ou et al., 2020 | Donor hair follicles from the adult occipital scalp | Biopsy sample of hair follicles | − | MSCs at 80% confluence were used. CM was then collected | Murine. Left and right body of each rat shaved as close as possible to the skin | Gel topically applied - Vehicle (control) - MSC-CM (n = 4/group) |
15 | Macroscopic appearance (photography), histology (HE) | No significant differences in hair growth were observed between MSC-CM and control group | MSC-CM-treated group showed a darker area of the skin and bigger diffusion. Histologically, the hair follicle cycling was enlarged in the MSC-CM-treated group |
| Park J. et al., 2019 | Human amniotic fluid | Amniocentesis performed for fetal karyotyping between 16- and 20-week gestation | IF and quantification (CD13+, CD29+, and CD44+). Osteogenic, adipogenic, and chondrogenic differentiation | MSCs of passage 3 at 70–80% confluence were used. CM was then collected | Murine. Plucking the dorsal skin of mice in the telogen phase of the hair cycle, inducing the second anagen stage | 50 μl topically applied - MSC-CM - MSC-Nanog-CM - Minoxidil 2% (control) (n = 3/group) |
10 | Macroscopic appearance (photography), histology (HE), IHC (ALP, CK15), qRT-PCR, WB (ALP, LEF1, and Versican) | The dorsal skin of MSC-Nanog-CM and minoxidil-treated mice was fully darkened, while bare spots were observed in MSC-CM group | MSC-Nanog-CM accelerated the telogen-to-anagen transition in HFs and increased HF density to a greater extent than MSC-CM. The expression of DP and HF stem cell markers and genes related to hair induction were higher in MSC-Nanog-CM than in AF-MSC-CM. Paracrine factors contained in MSC-Nanog-CM |
| upregulated the expression of hair induction genes and accelerated hair regeneration | ||||||||||
| Gunawardena et al., 2019 | hDP-MSCs: human deciduous teeth hHF-MSCs: human donor hair follicles | hDP-MSCs: teeth extraction hHF-MSCs: scalp biopsy | Flow cytometry (CD73+, CD90+, CD105+). Adipogenic, chondrogenic, osteogenic differentiation | SHED of passages 2–5 and HFSCs of passage 1 at 80% confluence were used. CM was then collected | Murine. Dorsal region shaved with clippers | 100 μl subcutaneously injected at the dorsal region every 3 days - hDP-MSCs -CM (n = 9) - hHF-MSC-CM (n = 9) - STK2 media, control (n = 3) - No treatment, control (n = 2) |
60 | Macroscopic appearance (photography) | hDP-MSC-CM-treated group showed a faster stimulation of hair growth in comparison with hHF-MSC-CM. The visual observance for the appearance of dark patches indicating the transition from telogen to anagen stage by hDP-MSC-CM ranged from 8 to 12 days while hHF-MSC-CM ranged from 12 to 15 days | VEGF-A and HGF were overexpressed in hDP-MSC-CM and hHF-MSC-CM group. No adverse events were reported |
| Choi et al., 2019 | Human adipose subcutaneous fat | Liposuction | − | MSCs were of passages 4–6 were used. Cells were seeded and treated with HB-EGF. CM was then collected. | Murine. Dorsal region shaved with clippers | Subcutaneously injected - ADSC-CM - ADSC-HB-EGF- CM (n = 4/group) |
17 | Macroscopic appearance (photography), histology (HE), IHC, qRT-PCR | MSC-CM and MSC-HB-EGF-CM promoted hair growth. MSC-HB-EGF-CM showed higher increase in hair weight | MSC-HB-EGF-CM more rapidly induced telogen-to-anagen hair cycling and showed higher number of mature hair follicles. Expression levels of several growth factors in the MSC-HB-EGF-CM were upregulated compared with MSC-CM group |
| Won et al., 2015 | Donor hair follicles | CELLnTEC | Flow cytometry (integrin a6 and CD71) | MSCs were obtained from CELLnTEC. MSCs were used | Murine. Dorsal side shaved with a clipper and electric shaver | Subcutaneously injected every 2 days - PBS (control) |
14 | WB | MSC-CM-treated group increased hair growth compared | MSC-CM enhanced the proliferation of HFs. The level of |
| at 100% confluence. CM was then collected | - MSC-CM (n = 5/group) | with controls | phosphorylated AKT and phosphorylated ERK1/2 was significantly increased after MSC-CM treatment | |||||||
| Shim, 2015 | Human dermal cells | − | Flow cytometry. Adipogenic, chondrogenic, osteogenic differentiation | MSCs of passage 2 were used. CM was then collected | Murine. Dorsal region shaved with a clipper | 100 μl topically applied daily - MSC-CM or - Minoxidil - Non-treated group (n = 6/group) |
35 | Visual scoring of hair growth | MSC-CM increased hair regeneration. After the follow-up, hair weight was around 20, 40, and 80 mg in control, minoxidil, and MSC-CM group, respectively | MSC-CM increased promoted early telogen-to-anagen phase conversion of hair follicles compared with minoxidil treated group and non-treated mice |
| Dong et al., 2014 | Murine bone marrow from the femur | Needle aspiration | Flow cytometry (CD29+, CD44+, CD73+, CD14−, CD34, CD45, CD133−). Adipogenic, chondrogenic, osteogenic differentiation | MSCs were transfected with murine Wnt1a cDNA retroviral vector. MSCs and Wnt1a-MSCs at 50–60% confluence were used. CM was collected from MSCs and Wnt1a-MSC- | Murine. Dorsal region shaved with a clipper | 100 ml intradermally injected - Wnt-CM - MSC-CM - DMEM (control) (n = 3/group) |
14 | Macroscopic appearance (photography), histology (HE), IHC, qRT-PCR | Both Wnt-CM and MSC-CM promoted the hair follicle cycling more than control group | Wnt-CM induces hair to enter earlier anagen of the hair cycle. ALP expression was enhanced in both MSC-CM and Wnt-CM group. More Ki67-positive cells were observed in Wnt-CM-treated mice. Both MSC-CM and Wnt-CM upregulated the hair induction-related genes |
| Won et al., 2010 | Human hair follicles | Dissection | IHC (alpha smooth muscle actin, alkaline phosphatase) | MSCs were transfected with plasmid carrying SV40T antigen and c-myc gene and neomycin-resistant gene. MSCs of passages 3–4 were used. CM was collected | Murine | Topical application - MSC-CM - DMEM (n = 3/group) |
21 | Macroscopic appearance (photography) | MSC-CM enhanced hair growth. Hair weight was 2- to 5-fold higher in MSC-CM compared with control group | MSC-CM accelerated hair growth |
| Park et al., 2010 | Human subcutaneous adipose tissue | Liposuction | − | MSCs of passages 4–5 were used. MSCs were cultured in nomoxic and hypoxic conditions. CM was then collected | Murine | Subcutaneously injected - Normoxic MSC-CM (n = 5) - Hypoxic MSC-CM (n = 5) - Control (n = 3) |
56 | Macroscopic appearance (photography) | MSC-CM increased hair regeneration compared with control | MSC-CM induced the anagen phase. Hair regeneration growth factors significantly increased by hypoxia |
ADSCs, adipose-derived stem cells; ADSVCs, adipose-derived stromal vascular cells; BM, bone marrow; DP, dermal papilla; hDPs, human dermal papilla cells; ECM, extracellular matrix; HF, hair follicle; hFDPs, human follicle dermal papilla cells; hHF-MSCs, human hair follicle mesenchymal stromal cells; hDSPC, human dermal stem/progenitor cell; hDP-MSC, human dental pulp mesenchymal stromal cells; IF, immunofluorescence IHC, immunohistochemistry; KSCs, keratinocyte stem/progenitor cells; MSCs, mesenchymal stromal cells, PBS, phosphate-buffered saline; SHED, dental pulp stem cells obtained from human deciduous teeth; SVF, stromal vascular fraction; WB, Western blotting.