"Strategic sequences" in adipose-derived stem cell nerve regeneration.

Background: Peripheral nerve injuries (PNI) are a major source of morbidity worldwide. The development of cellular regenerative therapies has the potential to improve outcomes of nerve injuries. However, an ideal therapy has yet to be found. The purpose of this study is to examine the current literature key points of regenerative techniques using human adipose-derived stem cells (hADSCs) for nerve regeneration and derive a comprehensive approach to hADSC therapy for PNI. Methods: A literature review was conducted using the electronic database PubMed to search for current experimental approaches to repairing PNI using hADSCs. Key search elements focused on specific components of nerve regeneration paradigms, including (1) support cells, (2) scaffolds, and (3) nerve conduits. Results: Strategic sequences were developed by optimizing the components of different experimental regenerative therapies. These sequences focus on priming hADSCs within a specialized growth medium, a hydrogel matrix base, and a collagen nerve conduit to achieve neuromodulatory nerve regeneration. hADSCs may exert their neuroregenerative influence through paracrine effects on surrounding Schwann cells in addition to physical interactions with injured tissue. Conclusions: hADSCs may play a key role in nerve regeneration by acting primarily as support for local neurotrophic mediation and modulation of nerve growth rather than that of a primary neuronal differentiation agent. V C 2013 Wiley Periodicals, Inc. Microsurgery 00:000‐000, 2013. The standard method of treatment of peripheral nerve injuries (PNI) with autologous nerve grafts has limitations, including donor site morbidity and suboptimal functional recovery. Tissue engineering provides an interesting alternative to current treatments and several variations of therapies have been studied, including nerve conduits, regenerative stimulants, and cellular components. However, intervening to change the natural physiologic course at this level requires a proper understanding of the timing and mechanisms of the events that occur during degeneration and regrowth after PNI. Nerve injury is accompanied by a sequence of events that precede the final outcome of nerve healing. 1 This outcome ranges from almost complete nerve regeneration to degeneration, nerve loss, neuroma formation, and incomplete or absent nerve regeneration. Each sequence within this nerve injury process is accompanied by biologic events that may influence the ongoing regenerative process. Thus, any strategy relating to nerve regeneration should consider these sequences individually and cumulatively as the process of regeneration unfolds. From this standpoint, it is pertinent to deconstruct PNI into sequences relating to degeneration, initial regeneration, and possible intervention strategies that may limit, speed up, or facilitate such sequences. This approach enables us to examine the process at different time frames and to plan combined approaches that consider most of these components when designing a comprehensive regenerative device. Human adipose tissue-derived stem cells (hADSCs) are a heterogeneous group of multipotent progenitor cells that can be harvested autogenously in high numbers with low donor site morbidity and have been used in several studies to promote nerve regeneration. 2‐6 This review focuses on the utilization of hADSCs as neurotrophic mediators, stimulating nerve regeneration from environmental cues rather than promoting the in vitro neuronal differentiation of hADSCs. The goal of this approach is to create an effective method of promoting nerve regeneration while minimizing the manipulation of autologous cells to move toward a transnational therapy.