Abstract

Mesenchymal stromal cells (MSCs) have unique immunomodulatory capacities. We investigated hair follicle-derived MSCs (HF-MSCs) from the dermal sheath, which are advantageous as an alternative source because of their relatively painless and minimally risky extraction procedure. These cells expressed neural markers upon isolation and maintained stemness for a minimum of 10 passages. Furthermore, HF-MSCs showed responsiveness to pro-inflammatory environments by expressing type-II major histocompatibility complex antigens (MHC)-II to a lesser extent than adipose tissue-derived MSCs (AT-MSCs). HF-MSCs effectively inhibited the proliferation of peripheral blood mononuclear cells equivalently to AT-MSCs. Additionally, HF-MSCs promoted the induction of CD4+CD25+FOXP3+ regulatory T cells to the same extent as AT-MSCs. Finally, HF-MSCs, more so than AT-MSCs, skewed M0 and M1 macrophages towards M2 phenotypes, with upregulation of typical M2 markers CD163 and CD206 and downregulation of M1 markers such as CD64, CD86, and MHC-II. Thus, we conclude that HF-MSCs are a promising source for immunomodulation.

Highlights

  • Mesenchymal stromal cells (MSCs) are proliferative and multipotent cells that exist in most tissues of the body and show numerous therapeutic properties

  • We evaluated the capacity of hair follicle-derived MSCs (HF-MSCs) to induce T regulatory differentiation as compared to adipose tissue-derived MSCs (AT-MSCs)

  • HFMSCs showed immunomodulatory potential equal to or exceeding that of AT-MSCs, inMSCs showed immunomodulatory potential equal to or exceeding that of AT-MSCs, includcluding inhibition of peripheral blood mononuclear cells (PBMCs) proliferation, suppression of cytotoxic T cell induction, proing inhibition of PBMC proliferation, suppression of cytotoxic T cell induction, promotion motion of regulatory T cell differentiation, and modulation of macrophage phenotype of regulatory T cell differentiation, and modulation of macrophage phenotype from M1 to from M1 to M2. These results suggest that HF-MSCs should be considered a viable alterM2. These results suggest that HF-MSCs should be considered a viable alternative to BMnative to BM- and AT-MSCs for therapies that rely on their immunomodulatory potential

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Summary

Introduction

Mesenchymal stromal cells (MSCs) are proliferative and multipotent cells that exist in most tissues of the body and show numerous therapeutic properties As their immunomodulatory potential has become increasingly appreciated through hundreds of clinical trials—reviewed in [1]—in recent years, a number of MSC cell therapies have been approved for clinical use, including Temcell® , Alofisel® , and Remestemcel-L—reviewed in [1,2]. MSCs have two important characteristics that make them an attractive therapeutic option for a wide range of inflammatory and immune-mediated diseases: immune evasion and immunomodulation. Their ability to evade immune rejection results from relatively 4.0/). The clinical potential of MSCs remains limited by numerous obstacles, including (i) the invasive and painful harvesting procedure with possible complications; (ii) their gradual loss of “stemness” and immunomodulatory properties during in vitro expansion; and (iii) their loss of immune evasiveness in inflammatory environments [7]

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