Mesenchymal stem cell-based therapy for peripheral nerve injuries: A promise or reality?

Abstract

Peripheral nerve injuries (PNI) that result in nerve gaps represent a major clinical challenge, frequently leading to long-term disability and a diminished quality of life for affected individuals. Despite advances in surgical techniques, functional recovery remains limited, highlighting the need for innovative therapeutic strategies. Mesenchymal stem cells (MSCs) have emerged as a promising avenue for nerve repair due to their regenerative, immunomodulatory, and neuroprotective properties. Thus, this review explored current approaches utilizing MSCs in the treatment of PNI, emphasizing their potential to enhance nerve regeneration and functional recovery. Furthermore, tissue engineering and transdifferentiation of MSCs into Schwann-like cells offer a versatile strategy to optimize therapeutic effects, paving the way for personalized medicine. Nevertheless, challenges persist regarding the clinical application of MSCs in PNI, including transplant safety, delivery methods, optimal dosing, and ethical considerations. A deeper understanding of the mechanisms underlying MSC action in PNI may contribute to more effective treatment protocols in the management of peripheral nerve defects.

Keywords: Cell-based therapies; Extracellular vesicles; Mesenchymal stem cells; Nerve guidance conduits; Nerve regeneration; Regenerative medicine.

Figure 1

Schematic representation of the grading systems for peripheral nerve injuries. Neuropraxia (Sunderland: Grade I) involves focal demyelination. Axonotmesis is subdivided into grade II (axon and myelin damage), grade III (axon, myelin, and endoneurium damage), and grade IV (axon, myelin, endoneurium, and perineurium damage). Neurotmesis (grade V) is complete nerve transection. Created in BioRender. Amorim, R. (2025) https://BioRender.com/z6uzrjj.

Figure 2

Endogenous regeneration process of the peripheral nervous system. Following injury, Wallerian degeneration occurs, and Schwann cells proliferate and transdifferentiate while acting alongside macrophages to remove cellular and myelin debris. For regeneration Schwann cells form Büngner’s bands and secrete neurotrophic factors that support axonal growth. Created in BioRender. Amorim, R. (2025) https://BioRender.com/z6uzrjj.

Figure 3

Schematic illustrating of the main mechanisms of mesenchymal stem cell action. Mesenchymal stem cell integration, paracrine activity, release of extracellular vesicles, mitochondrial transfer, and cell-cell contact. Created in BioRender. Amorim, R. (2025) https://BioRender.com/z6uzrjj.MSCs: Mesenchymal stem cells; EVs: Extracellular vesicles.

Figure 4

Summarized schematic of different designs to enhance nerve guidance conduits (NGCs). Design variations include hollow tubes, multichannel, porous, grooved structures, fiber, or hydrogel fillers. These designs can be used alone or in combination with mesenchymal stem cells or Schwann-like cells for the treatment of peripheral nerve injuries. NGCs: Nerve guidance conduits. Created in BioRender. Amorim, R. (2025) https://BioRender.com/z6uzrjj.