Human adipose-derived stem cells stimulate neuroregeneration

Abstract

Traumatic brain injuries and degenerative neurological disorders such as Alzheimer's dementia, Parkinson's disease, amyotrophic lateral sclerosis and many others are characterized by loss of brain cells and supporting structures. Restoring microanatomy and function using stem cells is a promising therapeutic approach. Among the many various sources, adipose-derived stem cells (ADSCs) are one of the most easily harvested alternatives, they multiply rapidly, and they demonstrate low immunogenicity with an ability to differentiate into several cell types. The objective of this study was to evaluate the effect of xenotransplanted human ADSCs on post-traumatic regeneration of rat sciatic nerve. Peripheral reconstruction following complete sciatic transection and autonerve grafting was complemented by intra-operative injection of hADSCs into the proximal and distal stumps. The injury caused gliosis and apoptosis of sensory neurons in the lumbar 5 (L5) ganglia in the control rodents; however, animals treated with hADSCs demonstrated a smaller amount of cellular loss. Formation of amputation neuroma, which hinders axonal repair, was less prominent in the experimental group, and immunohistochemical analysis of myelin basic protein showed good myelination 65 days after surgery. At this point, control groups still exhibited high levels of microglia/macrophage-specific marker Iba-1 and proliferating cell nuclear antigen, the mark of an ongoing inflammation and incomplete axonal growth 2 months after the injury. This report demonstrates that hADSCs promote neuronal survival in the spinal ganglion, fuel axonal repair and stimulate the regeneration of peripheral nerves.

The potential roles for adipose tissue in peripheral nerve regeneration

“…Rodents have an intrinsic ability to effectively regenerate nerves across short gaps; therefore, these experiments do not isolate the benefits of adding adipose tissue from the intrinsic ability of the nerve to regenerate itself. Furthermore, the clinical gold standard for repair of critical peripheral nerve gaps remains nerve autografts, and only one of the experiments evaluated the effectiveness of adipose tissue in supplementing nerve autografts . While this study demonstrated positive histological results, it lacked functional outcome measures.…”

“…Nineteen of the 23 experiments (83%) on cultured undifferentiated ASCs ( cuASCs) demonstrated a significant beneficial effect on nerve regeneration according to their primary outcome measures …”

“…Fourteen experiments examined the effects of cuASCs on nerve regeneration following injury to the sciatic nerve . Of the ten experiments that examined walking track and motor analysis, seven illustrated significant improvement compared with the controls.…”

“…Thirteen of the 14 experiments (93%) demonstrated significant improvements in histologic outcomes compared to controls. One of these 14 experiments evaluated the effects of cuASCs on enhancing regeneration of nerve gaps treated with autografts and demonstrated positive histological results, but lacked functional outcome measures …”

Current Status in Peripheral Nerve Xenotransplantation

“…A total of 22 articles were retrieved, all of them experimentally controlled studies in animals. Most studies used rats as host species [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Four studies used mice [16][17][18][19].…”