The Potential Role of Adipose-Derived Stem Cells in Regeneration of Peripheral Nerves

Abstract

Peripheral nerve injuries are common complications in surgical and dental practices, often resulting in functional deficiencies and reduced quality of life. Current treatment choices, such as autografts, have limitations, including donor site morbidity and suboptimal outcomes. Adipose-derived stem cells (ADSCs) have shown assuring regenerative potential due to their accessibility, ease of harvesting and propagation, and multipotent properties. This review investigates the therapeutic potential of ADSCs in peripheral nerve regeneration, focusing on their use in bioengineered nerve conduits and supportive microenvironments. The analysis is constructed on published case reports, organized reviews, and clinical trials from Phase I to Phase III that investigate ADSCs in managing nerve injuries, emphasizing both peripheral and orofacial applications. The findings highlight the advantages of ADSCs in promoting nerve regeneration, including their secretion of angiogenic and neurotrophic factors, support for cellular persistence, and supplementing scaffold-based tissue repair. The regenerative capabilities of ADSCs in peripheral nerve injuries offer a novel approach to augmenting nerve repair and functional recovery. The accessibility of adipose tissue and the minimally invasive nature of ADSC harvesting further encourage its prospective application as an autologous cell source in regenerative medicine. Future research is needed to ascertain standardized protocols and optimize clinical outcomes, paving the way for ADSCs to become a mainstay in nerve regeneration.

Keywords: adipose tissue-derived stem cells; adipose-derived stromal cells; nerve conduits; peripheral nerve injury; peripheral nerve repair and regeneration; regenerative medicine.

Figure 1

Schematic diagram details the microanatomy and classifications of peripheral nerve injuries (PNI), including both Sunderland and Seddon classifications. The image underscores that the peripheral nervous system (PNS) is not an independent entity and requires the central nervous system (CNS) for repair and regeneration. The intricate network of peripheral nerves, which are structured into fascicles and enclosed within multi-layered shielding sheaths by specialized cells like Schwann cells and fibroblasts, necessitates substantial support for the regenerative process.

Figure 2

The illustration features Wallerian degeneration at the individual nerve level in both myelinated and unmyelinated nerves. Post-injury, the perikaryon in the CNS will endure chromatolysis: The cell body swells; the nucleus becomes eccentric; and Nissl granules disperse. When needed, microglia cells, astrocytes, and oligodendrocytes are recruited to aid in the recovery of the nerve body. At the PNS level, the injury site divides the axon into a proximal segment, which is continuous with the cell body in the CNS, and a distal segment which is disconnected from the cell body. Wallerian degeneration begins with the fragmented axons initiating modifications in the Schwann cells and recruiting macrophages to remove the damaged myelin and axon debris. These changes are marked by a fluid phase that accumulates defense and scavenger cells around the injured site. Later, during the cellular phase, the Schwann cells guide the sprouting axons by forming bands of Büngner to prune and guide them. The process continues until regeneration is complete.

Figure 3

The role of adipose-derived stem cells (ADSCs) in nerve repair and regeneration. ADSCs are derived from adipose tissue and contain mesenchymal stromal cells (MSCs), including fibroblasts, smooth muscle cells, endothelial cells, and mast cells. ADSCs release neurotrophic factors, neural stem cells, and growth factors like bFGF, VEGF, HGF, TGF-β, and Angiopoietin 1, which promote nerve regeneration, neuroprotection, Schwann cell-like differentiation, and vascularization. These mechanisms collectively support blood vessel formation, preservation of neuronal integrity, Schwann cell development, and functional recovery of damaged nerves.

Figure 4

The use of nerve conduits made from synthetic and natural materials for nerve repair based on injury length. Synthetic materials include nonbiodegradable polymers (e.g., silicone, polytetrafluoroethylene) and biodegradable polymers (e.g., PGA, PLA, PCL), offering strength but with disadvantages like the need for secondary surgeries and potential foreign body reactions. Natural materials, such as collagen, gelatin, and alginate, exhibit intrinsic cell adhesion properties and compatibility with tissue repair. For extended injuries, conduits integrated with adipose-derived stem cells (ADSCs) and hydrogels (e.g., polyethylene glycol, chitosan) support regeneration by providing extracellular matrix (ECM) scaffolding, promoting nerve repair through enhanced cell growth and vascularization.