“Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model” – Experimental research

Abstract

Background Optimizing nerve regeneration and mitigating muscle atrophy are the keys to successful outcomes in peripheral nerve damage. We investigated whether mesenchymal stem cell (MSC) therapy can improve limb function recovery in peripheral nerve damage. Materials and methods We used sciatic nerve transection/repair (SNR) and individual nerve transection/repair (INR; branches of sciatic nerve - tibial, peroneal, sural) models to study the effect of MSCs on proximal and distal peripheral nerve damages, respectively, in male Lewis rats. Syngeneic MSCs (5 × 10 6 ; passage≤6) or saline were administered locally and intravenously. Sensory/motor functions (SF/MF) of the limb were assessed. Results Rat MSCs (>90%) were CD29 + , CD90 + , CD34 − , CD31 − and multipotent. Total SF at two weeks post-SNR & INR with or without MSC therapy was ∼1.2 on a 0–3 grading scale (0 = No function; 3 = Normal); by 12 weeks it was 2.6–2.8 in all groups (n ≥ 9/group). MSCs accelerated SF onset. At eight weeks post-INR, sciatic function index (SFI), a measure of MF (0 = Normal; −100 = Nonfunctional) was −34 and −77 in MSC and vehicle groups, respectively (n ≥ 9); post-SNR it was −72 and −92 in MSC and vehicle groups, respectively. Long-term MF (24 weeks) was apparent in MSC treated INR (SFI -63) but not in SNR (SFI -100). Gastrocnemius muscle atrophy was significantly reduced (P < 0.05) in INR. Nerve histomorphometry revealed reduced axonal area (P < 0.01) but no difference in myelination (P > 0.05) in MSC treated INR compared to the naive contralateral nerve. Conclusion MSC therapy in peripheral nerve damage appears to improve nerve regeneration, mitigate flexion-contractures, and promote limb functional recovery.

Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies

“…Animal housing, husbandry and experiments were conducted as per the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978) following approval by the Institutional Animal Care and Use Committee (IACUC), as per protocol (No.215064) and institutional guidelines similar to previously published reports [ 5 ]. The report presented is as per the ARRIVE (Animal Research: Reporting In Vivo Experiments) protocols [ 37 ].…”

“…We used a sciatic nerve repair (SNR) model that involved transection of the main sciatic nerve just above the trifurcation into tibial, sural, and peroneal branches as described previously [ 5 ]. SNR was performed on the right hind limb, and the left naïve limb served as a non-transected nerve control.…”

“…There are several alternative approaches emerging to promote peripheral nerve repair including stem cell administration [ 9 , 11 , 13 , 25 , 26 , 28 , 40 , 45 , 56 , 57 , 59 , 60 , 69 , 70 , 86 ]. However, the role of stem cells on peripheral nerve regeneration is not completely understood; a combination of trophic factor production, extracellular matrix synthesis, axon guidance, remyelination, microenvironmental stabilization, and/or immune modulation support mediated by stem cells appear to promote peripheral nerve regeneration and function [ 5 , 8 , 10 , 12 , 26 , 42 , 44 , 47 , 55 , 56 , 59 , 61 ]. Mesenchymal stem cells (MSCs) have been shown to improve functional recovery in animal models of nervous system diseases (Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, spinal cord injury) including peripheral nerve damage [ 5 , 14 , 19 , 36 , 71 ].…”

Human stem cells – sources, sourcing and in vitro methods

“…After the procedure, the rBM-MSCs were injected in the dorsal penile vein and readministered for 3 weeks with one-week interspace between doses. The rBM-MSCs could improve restoration of extremity function and promote the nerve recovery [80]. The rBM-MSCs have been used in diabetic ischemic wound treatment on the dorsal region of foot of noninsulin-dependent diabetes mellitus in a rat model.…”

Immunological and Hematological Response to Local Transplantation of Stem Cells in Injured Radial Nerve of Dogs

“…Enervated muscle atrophy is still a major problem in the field of peripheral NI repair. Functional recovery is of utmost importance for limb rescue in the management of peripheral NIs that range from compression to complete nerve transection with no continuity of any neural structure (8). The inflammatory response to the injury affects tissue regeneration and has become an important factor influencing the prognosis of patients.…”