Transplantation of adipose-derived stem cells for peripheral nerve repair

Abstract

Abstract. Mesenchymal stem cells have become a very attractive source of cell implantation for neural tissue engineering. The ideal stem cells for transplantation should be easily obtained, and should rapidly proliferate in vitro and have low immunogenicity. The purpose of this study was to investigate the regenerative potential of adipose-derived stem cells (ADSC) on peripheral nerve repair. ADSCs were isolated from rat adipose tissue and cultured until adherent cells became morphologically homogeneous with a fibroblast-like shape, and transplanted with acellular nerve allografts (ANAs) into rat models with a 10 mm gap of transected sciatic nerve defect. After cell transplantation, we found that ADSC implantation improved functional recovery of exercise behavior and increased wet weight ratio of the anterior tibial muscle. In the electrophysiological testing, we found that the percentage of activated fibers was higher in the ADSC-implanted animals as evidenced by the increase of nerve conduction velocity and amplitude. Histological examination revealed that the number of nerve fibers, axonal diameter and myelin thickness were significantly higher in the ADSC-implanted animals compared to the control. In addition, we demonstrated that the progression of the regenerative process after ADSC implantation was accompanied by elevated expression of neurotrophic factors at both the early and later phase. Taken together, these results suggest that ADSCs can promote the repair of peripheral nerve injury, and the combination of ADSC and ANA transplantation is a new therapeutic method for long distant peripheral nerve defects. Our data also provide evidence indicating the strong association of neurotrophic factor production to the regenerative potential of implanted ADSCs. IntroductionTraditional therapeutic approaches for the reconstruction of peripheral nerve defects include end-to-end suturing, fascicular suturing, nerve graft, and nerve conduits. There is evidence indicating that nerve grafting is essential for reconstruction of long nerve defects. Recently, neural tissue engineering has received much attention, and Schwann cell transplantation has been reported to achieve reliable outcomes in the regeneration of the sciatic nerve (1-3). However, Schwann cell isolation can cause additional damage, and these cells need a long time for cell culture and growth, which have limited their clinical application.Mesenchymal stem cells (MSC) have recently become a very attractive source of cell implantation for tissue engineering because of their self-proliferation, fast proliferation and multilineage differentiation potential (4). A large number of studies have shown that bone marrow-derived mesenchymal stem cells (BMMSC) can promote the repair of peripheral nervous system injury (5-11). Chen et al (11) found that rat BMMSC can synthesize and secrete a number of neurotrophic factors (NF), including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factors (CNTF) and glial cell line-derive...

Effects of Canine and Murine Mesenchymal Stromal Cell Transplantation on Peripheral Nerve Regeneration

“…Therefore, the absence of muscle recovery in the MSC treated groups might be justified by an insufficient time to achieve complete muscle reinnervation (24). …”

“…However, several studies using MSC-based therapy showed positive effects in the sciatic nerve regeneration 6 to 12 weeks after neurotmesis varying from 3-to-10–mm nerve gap (6, 8, 23, 24, 26, 38–40). Our results are in accordance with these findings, indicating that after a neurotmesis of 10 mm, the nerve regeneration is enhanced by MSC transplantation, even in a short period of 35 days.…”

3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

“…In vivo experiments also confirmed a benefit of applying the ASCs in promoting nerve regeneration after transplanted into the injured site. Several previous studies have demonstrated the utilization of ASCs improved axonal regeneration in vivo , and this effect has been attributed mainly to the environmental support provided by the ASCs during nerve regeneration44454647.…”

Perspectives on the Use of Mesenchymal Stem Cells in Vascularized Composite Allotransplantation

“…MSCs have shown promise in improving clinical and electrophysiological outcomes in animal models of peripheral nerve injury (37–39). In comparison to local delivery, some groups have demonstrated significantly accelerated functional neuronal recovery following systemic administration of MSCs (40).…”