Differentiation of adipose-derived stem cells into Schwann cell-like cells through intermittent induction: potential advantage of cellular transient memory function

Xun Sun,Shi-Bi Lu,He-Yong Yin,Feng Xu,Zhi-Yuan Guo,Jiang Peng,Bo Xiao,Yu Wang,Yun Zhu,Wen-Li Jiang,Wei-Min Guo,Hao-Ye Meng

doi:10.1186/s13287-018-0884-3

Abstract

BackgroundPeripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Tissue engineering technology is a novel therapeutic strategy, and mesenchymal stromal cells (MSCs) are promising seed cells for nerve tissue engineering. However, the efficiency of traditional methods for inducing the differentiation of MSCs to Schwann cell-like cells (SCLCs) remains unsatisfactory.MethodsHere, we propose an intermittent induction method with alternate use of complete and incomplete induction medium to induce differentiation of adipose-derived stem cells (ASCs) to SCLCs. The time dependence of traditional induction methods and the efficiency of the intermittent induction method and traditional induction methods were evaluated and compared using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and co-culture with the dorsal root ganglion (DRG) in vitro. Cell transplantation was used to compare the effects of the traditional induction method and the intermittent induction method in repairing sciatic nerve defects in vivo.ResultsThe results of the present study indicated that the intermittent induction method is more efficient than traditional methods for inducing ASCs to differentiate into SCLCs. In addition, SCLCs induced by this method were closer to mature myelinating Schwann cells and were capable of secreting neurotrophins and promoting DRG axon regeneration in vitro. Furthermore, SCLCs induced by the intermittent induction method could repair sciatic nerve defects in rats by cell transplantation in vivo more effectively than those produced by traditional methods.ConclusionIntermittent induction represents a novel strategy for obtaining seed cells for use in nerve tissue engineering.

Highlights

Peripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden
Identification of adipose-derived stem cells Primary Adipose-derived stem cell (ASC) grew in clusters and had a rounded spindle-like shape (Fig. 1a)
ASCs at passage 2 could differentiate into adipocytes, and the visual field in photographs was filled with red lipid droplets stained with Oil Red O solution (Fig. 1b)

Summary

Introduction

Peripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Peripheral nerve injury (PNI) affects 1 million people every year worldwide [1, 2]. There are nearly 300,000 traumatic PNI cases in Europe every year. Endto-end suturing is sufficient for treatment in cases of simple nerve transection. Autologous nerve grafting is the gold standard treatment for this type of PNI [5, 6]. There are a number of technical limitations in autologous nerve grafting, such as limited donor sources, complications from second operations, and risk of painful neuroma formation [5, 9, 10]. Peripheral nerve repair using synthetic or bioderived transplants has aroused widespread attention

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