"Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model" - Experimental research

Jason R Bingham; Kevin R Kniery; Nikolas L Jorstad; Iren Horkayne-Szakaly; Zachary S Hoffer; Shashikumar K Salgar

doi:10.1016/j.amsu.2019.03.009

"Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model" - Experimental research

Ann Med Surg (Lond). 2019 Mar 28:41:20-28. doi: 10.1016/j.amsu.2019.03.009. eCollection 2019 May.

Authors

Jason R Bingham¹, Kevin R Kniery¹, Nikolas L Jorstad², Iren Horkayne-Szakaly³, Zachary S Hoffer⁴, Shashikumar K Salgar⁵

Affiliations

¹ Department of Surgery, Madigan Army Medical Center, Tacoma, WA, 98431, USA.
² Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
³ Department of Neuropathology & Ophthalmic Pathology, Joint Pathology Center, Defense Health Agency, Silver Spring, MD, 20910, USA.
⁴ Department of Pathology, Madigan Army Medical Center, Tacoma, WA, 98431, USA.
⁵ Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA, 98431, USA.

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 × 10⁶; 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.

Keywords: Cell therapy; Mesenchymal stem cells; Microsurgery; Motor function; Rat; Sciatic nerve repair.