American Society for Peripheral Nerve

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Stem Cell-Derived Exosomes: A New Option in the Treatment of Peripheral Nerve Injury?
Rosanna C Ching, MBChB; Mikael Wiberg, MD, PhD; Paul J Kingham, PhD
Umea University, Umea, Sweden

Introduction: Aiming to develop new treatment strategies that could speed up regeneration and guide axons across nerve gaps, we have explored the effect that exosomes from adipose-derived stem cells (ASC) have on neurite outgrowth. Functional recovery following a significant peripheral nerve injury continues to be inadequate. This impacts considerably on both patients and society as sufferers are commonly young workers. Poor outcomes often are due to the proximity of the injury and subsequent length to regenerate, or secondary to a nerve gap injury. We propose exosomes (nanovesicles involved in intercellular communication) could contribute to the management of such injuries.

Materials and Methods: Rat ASCs were differentiated into Schwann cell-like cells (dASCs). Exosomes from both Schwann cells (SCs) and dASCs were isolated and applied to neurons in vitro. Computerised image analysis assessed neurite outgrowth after 24 hours for comparison against a control group. The exosome cargo was also investigated for RNAs involved in nerve regeneration through RT-PCR techniques.

Results: Neurons incubated with either SC or dASC exosomes showed significantly longer neurites after 24 hours than the control group (Figure 1). SC and dASC exosomes both transport microRNA and mRNA cargo that has a role in nerve regeneration, and these neurons were shown to internalise this RNA carried.

Fig.1: Neurons incubated with either SC or dASC exosomes produced longer neurites compared to control (p<0.05).

Conclusions: dASC exosomes increase neurite outgrowth in vitro, mirroring the proven success of their SC counterparts. The RNAs within these exosomes likely coordinate this regenerative enhancement. Potential applications of this for clinical use could include direct injections of dASC exosomes to primary repairs of simple injuries, or in combination with synthetic conduits for nerve gaps. Such methods could overcome the concerns of harvesting a functioning nerve for an autologous graft, and avoid the numerous problems associated with using stem cells themselves.

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