Adipose-Derived Stem Cells Produce Factors Enhancing Peripheral Nerve Regeneration: Influence of Age and Anatomic Site of Origin

Abstract

Adipose-derived stem cells (ADSCs) are attracting increased attention as a novel source in regenerative medicine. Transplantation of ADSCs promotes functional recovery in animal models of peripheral nerve injury, but the mechanism of enhanced nerve regeneration remains to be elucidated. In addition, it is important to examine whether the supportive functions of ADSCs are dependent on donor age or anatomic site of origin. In this study, we examined the effects of factors produced by mouse ADSCs on Schwann cells (SCs) and dorsal root ganglion (DRG) neurons in vitro and compared these effects among ADSCs from donors of different age and from different anatomic regions. ADSC-derived soluble factors supported survival and proliferation of SCs and promoted neurite outgrowth in DRG neurons. These beneficial effects were far superior to that of factors from 3T3-L1 cells and comparable to those of SC- and astrocyte (AC)-derived factors. ADSCs from different sources similarly retained their neurotrophic activity. Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay analyses demonstrated that ADSCs produced various growth factors, some of which were more abundant than in SCs and ACs. These results suggest that ADSCs promote peripheral nerve regeneration partly through paracrine secretion of trophic factors and regardless of donor age or anatomic site of origin.