Bone marrow‐derived mesenchymal stem cells prevent alopecia areata development through the inhibition of NKG2D expression: A pilot study

Anagen stage hair follicles (HFs) exhibit “immune privilege (IP)” from the level of the bulge downwards to the bulb. Both passive and active IP mechanisms protect HFs from physiologically undesired immune responses and limit immune surveillance. IP is relative, not absolute, and is primarily based on absent, or greatly reduced, intra‐follicular antigen presentation via MHC class I and II molecules, along with prominent expression of “no danger” signals like CD200 and the creation of an immunoinhibitory signalling milieu generated by the secretory activities of HFs. Perifollicular mast cells, Tregs and other immunocytes may also contribute to HF IP maintenance in healthy human skin. Collapse of anagen hair bulb IP is an essential prerequisite for the development of alopecia areata (AA). In AA, lesional HFs are rapidly infiltrated by NKG2D + T cells and natural killer (NK) cells, while perifollicular mast cells acquire a profoundly pro‐inflammatory phenotype and interact with autoreactive CD8+ T cells. Using animal models, significant functional evidence has accumulated that demonstrates the dominance of the immune system in AA pathogenesis. Purified CD8+T‐cell and NK cell populations alone, which secrete fγ, suffice to induce the AA phenotype, while CD4+T‐cells aggravate it, and Tregs and iNKT cells may provide relative protection against AA development. While IP collapse may be induced by exogenous agents, inherent IP deficiencies might confer increased susceptibility to AA for some individuals. Thus, a key goal for effective AA management is the re‐establishment of a functional HF IP, which will also provide superior protection from disease relapse.

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“…Use mesenchymal cells with inherent IP to re‐establish HF antigen tolerance in autoreactive T cells 351,352,383 …”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Hair follicle immune privilege and its collapse in alopecia areata

Bertolini

McElwee

Gilhar

et al. 2020

Experimental Dermatology

182

157

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“…Stem cell‐based therapies have gained tremendous attention owing to their advantages of infinite self‐renewal capacity and multi‐lineage differential potential, 6 thereby providing approaches to coping with the challenges posed by traditional alopecia therapies. Mesenchymal stem cells (MSCs) show considerable promise for intravenous injection of human MSCs into non‐scarring alopecia 12 and co‐culture with human dermal papilla cells (hDPCs) 13 , 14 in preclinical studies. Moreover, using conditioned medium from cells (eg, Wnt1a, 15 , 16 Wnt7a, 17 or Nanog‐overexpressing MSCs 18 ) can accelerate the telogen‐to‐anagen transition of HFs.…”

Section: Introductionmentioning

confidence: 99%

Amphiregulin promotes hair regeneration of skin‐derived precursors via the PI3K and MAPK pathways

Gao

Fan

et al. 2021

Cell Proliferation

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Objectives There are significant clinical challenges associated with alopecia treatment, including poor efficiency of related drugs and insufficient hair follicles (HFs) for transplantation. Skin‐derived precursors (SKPs) exhibit great potential as stem cell‐based therapies for hair regeneration; however, the proliferation and hair‐inducing capacity of SKPs gradually decrease during culturing. Materials and Methods We describe a 3D co‐culture system accompanied by kyoto encyclopaedia of genes and genomes and gene ontology enrichment analyses to determine the key factors and pathways that enhance SKP stemness and verified using alkaline phosphatase assays, Ki‐67 staining, HF reconstitution, Western blot and immunofluorescence staining. The upregulated genes were confirmed utilizing corresponding recombinant protein or small‐interfering RNA silencing in vitro, as well as the evaluation of telogen‐to‐anagen transition and HF reconstitution in vivo. Results The 3D co‐culture system revealed that epidermal stem cells and adipose‐derived stem cells enhanced SKP proliferation and HF regeneration capacity by amphiregulin (AREG), with the promoted stemness allowing SKPs to gain an earlier telogen‐to‐anagen transition and high‐efficiency HF reconstitution. By contrast, inhibitors of the phosphoinositide 3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) pathways downstream of AREG signalling resulted in diametrically opposite activities. Conclusions By exploiting a 3D co‐culture model, we determined that AREG promoted SKP stemness by enhancing both proliferation and hair‐inducing capacity through the PI3K and MAPK pathways. These findings suggest AREG therapy as a potentially promising approach for treating alopecia.

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“…Immunologic disturbances use HF as one of their main targets. When the HF immune privilege is collapsed, CD4 and CD8 T cells and natural killer (NK) cells accumulate around the autoantigens of the hair bulb and contribute to the development of AA [35,36]. Multiple models have shown the association between the development of several types of alopecia with the disruption of certain cytokines and proteins.…”

Section: Mesenchymal Stem Cell Therapymentioning

confidence: 99%

“…Serum samples also showed decreased IFNγ, CXCL9, and CXCL10 concentrations in the treated group. Moreover, histological analysis demonstrated less inflammatory cellular infiltration around the dermal papilla [35]. Later, Kim et al launched another in vitro study with the aim of assessing the effect of hMSCs on the viability and proliferation of human dermal papilla cells (hDPC) via the activation of the JAK/STAT and Wnt/beta-catenin signaling pathways in an AA-model.…”

Section: Mesenchymal Stem Cell Therapymentioning

confidence: 99%

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

Martínez-López

Montero‐Vílchez

Sierra-Sánchez

et al. 2020

IJMS

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Alopecia is a challenging condition for both physicians and patients. Several topical, intralesional, oral, and surgical treatments have been developed in recent decades, but some of those therapies only provide partial improvement. Advanced medical therapies are medical products based on genes, cells, and/or tissue engineering products that have properties in regenerating, repairing, or replacing human tissue. In recent years, numerous applications have been described for advanced medical therapies. With this background, those therapies may have a role in the treatment of various types of alopecia such as alopecia areata and androgenic alopecia. The aim of this review is to provide dermatologists an overview of the different advanced medical therapies that have been applied in the treatment of alopecia, by reviewing clinical and basic research studies as well as ongoing clinical trials.

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Bone marrow‐derived mesenchymal stem cells prevent alopecia areata development through the inhibition of NKG2D expression: A pilot study

Cited by 15 publications

References 8 publications

Hair follicle immune privilege and its collapse in alopecia areata

Hair follicle immune privilege and its collapse in alopecia areata

Amphiregulin promotes hair regeneration of skin‐derived precursors via the PI3K and MAPK pathways

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

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