The Functional Outcomes of Nerve Allografts Seeded With Differentiated and Undifferentiated Mesenchymal Stem Cells

Abstract

Grant support received from: 2016 AFSH Basic Science Grant Royalty: Mayo Medical Ventures/TriMed Orthopedics (Shin) As decelullarized nerve allografts lag biological support of cells, we hypothesized that the addition of either undifferentiated mesenchymal stem cells (uMSCs) or mesenchymal stem cells differentiated into Schwann-like cells (dMSCs) would enhance nerve regeneration and improve functional outcomes of nerve allografts. Sciatic nerve segments of 80 rats were reconstructed with (1) autografts, (2) decellularized allografts, (3) decellularized allografts seeded with undifferentiated MSCs, or (4) decellularized allografts seeded with differentiated MSCs. Nerve regeneration was quantified by longitudinal ultrasound measurements of the cross-sectional tibial muscle area. At 12 and 16 weeks after surgery, functional outcome measurements (compound muscle action potentials [CMAP], isometric tetanic force measurement [ITF], muscle mass and histological analyses) were performed (Figure 45-1). All outcomes are expressed as a percentage of the contralateral side. 2-way repeated measures ANOVA was used to analyze the ultrasound measurements and a 2-point ANOVA was used to analyze all other outcomes. Post-hoc multiple comparisons analyses were corrected by the Benjamini-Hochberg procedure. Cross-sectional muscle area, CMAP, ITF, muscle mass, and histological measurements demonstrated a beneficial effect of MSC seeding, but only the CMAP recovery (P < .004) and Schwann cell intensity (P < .021) were significantly better in the groups seeded with MSCs compared with unseeded grafts. The differences between uMSCs and dMSCs were not significantly different. The autograft was partially superior to the seeded grafts concerning angle contracture recovery (P = .005), muscle mass (P = .006), and some histological measurements (P < .015), but the outcomes measured by cross-sectional muscle area, ITF, and the remaining histological analysis did not significantly differ from the seeded allografts. •Unseeded allografts significantly underperformed on almost all outcome measures when compared with the seeded grafts.•The differentiation state of seeded MSCs did not alter the functional outcomes.•Autografts remain the reference standard.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This research was supported by a Basic Science Grant from the American Foundation for Surgery of the Hand.