Human bone marrow‐derived MSCs spontaneously express specific Schwann cell markers

Abstract

In peripheral nerve injuries, Schwann cells (SC) play pivotal roles in regenerating damaged nerve. However, the use of SC in clinical cell‐based therapy is hampered due to its limited availability. In this study, we aim to evaluate the effectiveness of using an established induction protocol for human bone marrow derived‐MSC (hBM‐MSCs) transdifferentiation into a SC lineage. A relatively homogenous culture of hBM‐MSCs was first established after serial passaging (P3), with profiles conforming to the minimal criteria set by International Society for Cellular Therapy (ISCT). The cultures (n = 3) were then subjected to a series of induction media containing β‐mercaptoethanol, retinoic acid, and growth factors. Quantitative RT‐PCR, flow cytometry, and immunocytochemistry analyses were performed to quantify the expression of specific SC markers, that is, S100, GFAP, MPZ and p75 NGFR, in both undifferentiated and transdifferentiated hBM‐MSCs. Based on these analyses, all markers were expressed in undifferentiated hBM‐MSCs and MPZ expression (mRNA transcripts) was consistently detected before and after transdifferentiation across all samples. There was upregulation at the transcript level of more than twofolds for NGF, MPB, GDNF, p75 NGFR post‐transdifferentiation. This study highlights the existence of spontaneous expression of specific SC markers in cultured hBM‐MSCs, inter‐donor variability and that MSC transdifferentiation is a heterogenous process. These findings strongly oppose the use of a single marker to indicate SC fate. The heterogenous nature of MSC may influence the efficiency of SC transdifferentiation protocols. Therefore, there is an urgent need to re‐define the MSC subpopulations and revise the minimal criteria for MSC identification.

CXCL12/CXCR4 facilitates perineural invasion via induction of the Twist/S100A4 axis in salivary adenoid cystic carcinoma

“…Accumulating evidences have indicated that tumour cells differentiating towards Schwann‐like cell could accelerate the predisposition for PNI of tumours. 19 , 37 , 38 , 39 In this study, the level of S100A4, p75NTR and GFAP, which had been characterized as Schwann cell markers, 11 , 12 was evidently increased at nerve invasion frontier. And the relevancy analysis indicated that CXCR4 expression level was positively correlated with S100A4, p75NTR and GFAP level at nerve invasion front.…”

“…Schwann cells are fundamental to the merisis and luxuriance of nerves and conducive to the guidance of axons. 11 , 12 A growing body of evidence showed that the level of Schwann cell hallmarks, including glial fibrillary acidic protein (GFAP), p75 neurotrophin receptor (p75NTR), S100 calcium‐binding protein A4 (S100A4), was significantly increased in many tumour with PNI, including melanoma, 13 breast cancer, 14 prostate cancer, 15 colorectal cancer. 16 Hence, researchers inferred that the differentiation of cancer cell towards Schwann‐like cell might be responsible for the PNI occurrence of tumours.…”

MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma

“…Schwann cells, which constituted the main cells of peripheral nerve, are essential for peripheral nerve survival and development and related to the maintenance of axons. Studies showed that the expression of Schwann cell biomarkers, including S100 calcium binding protein A4 (S100A4), p75 neurotrophin receptor (p75NTR), and glial fibrillary acidic protein (GFAP) was involved in occurrence and metastasis of tumors through increased migration and invasion capabilities . Furthermore, a large body of evidence showed that S100A4 was evidently increased in tumors with PNI, such as melanoma, colorectal cancer, prostate cancer, breast carcinoma .…”

Tacrolimus-Induced Neurotrophic Differentiation of Adipose-Derived Stem Cells as Novel Therapeutic Method for Peripheral Nerve Injury

“…It is very true that we can hardly say or judge the differentiation efficiency of ADSCs simply via S100β. As the previous study mentioned, many Schwann cell markers (e.g., GFAP, P75NGFR, MPZ, and S100β) can be employed to characterize Schwann cell phenotype, but all of these markers had low expression (less than 15%) following the established neural induction protocol ( Ramli et al, 2019 ). The accurate characterization of Schwann cell-like differentiation may require more rigorous assessments (including but not limited to Schwann cell specific markers and transcription factors listed above).…”