Effects of mesenchymal stem cell therapy on alopecia areata in cellular and hair follicle organ culture models

Abstract

Mesenchymal stem cell therapy (MSCT) has been suggested as a new therapeutic strategy for immunological disorders. There have been only a few attempts to treat alopecia areata (AA) with MSCT. MSCT efficacy and mechanism of action in treating AA are not known. We sought to investigate the effect of human hematopoietic mesenchymal stem cells (hHMSCs) on an in vitro model of AA and to explore relevant mechanisms that regulate efficacy. An AA‐like environment was induced by pretreatment of human dermal papilla cells (hDPCs) with interferon gamma (IFN‐γ). hHMSCs were administered to the hDPCs, and cell viability was determined. Similar studies were also conducted with human hair follicles (HFs) in culture. The change in expression of the Wnt/β‐catenin pathway and JAK/STAT pathway‐related molecules and growth factors in hHMSC‐treated hDPCs was also examined by reverse transcription‐PCR, Western blot assay and growth factor array. Immune privilege–related molecules were examined by immunohistochemistry in HF culture models. hHMSCs enhanced the cell viability of the hDPCs. hHMSCs activated several molecules in the Wnt/β‐catenin signalling pathway, including ß‐catenin and phosphorylated GSK3b, and decreased IFN‐γ‐induced expression of DKK1 in hDPCs. hHMSCs suppressed IFN‐γ‐induced expression of caspase‐1, caspase‐3 and IFN‐γ receptor. hHMSCs induced the phosphorylation of STAT1 and STAT3 compared to controls and IFN‐γ–pretreated hDPCs. hHMSC‐treated HFs enhanced several growth factor mRNAs. hHMSC pretreatment modulated IFN‐γ–induced expression of molecules related to HF immune privilege on HFs in organ culture. These data suggest MSCT may be a new potential therapeutic option in treating AA.

The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells

“…Six-week-old male C57BL/6 mouse vibrissae follicles were microdissected under sterile conditions, as previously described [ 20 ]. Individual follicles were placed in a 24-well tissue culture plate in Williams E medium, which was supplemented with hydrocortisone, insulin, and glutamine in the presence of DMSO, IFN-γ, or ruxolitinib.…”

Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models

“…Cultures of freshly micro‐dissected human scalp hair follicles, which are a special variant of skin explant culture, have been successfully used to study aspects of human hair biology not displayed in the animal models and have been instructive for our understanding of human hair follicle physiology and pathology (Figure 1C) 76,77 . Studies on human hair follicle organ cultures are commonly featured in this journal, including recent works that examined hair growth‐promoting effect of dermal papilla‐derived exosomes, 78 regulation of hair follicle immune privilege 79 and modulation of hair growth by the blue light‐sensitive circadian clock factor CRY1 80 …”

Advanced Medical Therapies in the Management of Non-Scarring Alopecia: Areata and Androgenic Alopecia

“…In addition, hMSC treatment augmented beta-catenin levels and induced much higher phosphorylation of STAT1 and STAT3, proteins that are associated with a prolonged anagen phase. Finally, the investigators observed an immunomodulatory effect in the treatment with hMSC by restoring a HF privilege that induced re-entry signaling from the telogen to anagen phase [43]. Recently, Bak et al conducted a mice-based study in order to evaluate the effect of umbilical cord blood hMSCs on reacquisition of hDPC conduction ability to induce hair growth.…”