MESENCHYMAL STEM CELLS AND CELLULAR TRANSPLANTATION

G. Brzezicki, A. Jundzill, A. Mendiola, A. Klimczak, J. Gatherwright, M. Siemionow
Plastic And Reconstructive Surgery, Cleveland Clinic, Cleveland/UNITED STATES OF AMERICA

Body: Introduction Limited source of autografts available for transfer and donor site morbidity after harvesting the grafts warrants further research on new methods of nerve repair. Allogenic epineural tube supported with BMSC may be a valuable alternative for nerve gap repair. The aim of this study is to assess the outcome of peripheral nerve repair with allogenic tube supported with BMSC. Methods 18 fully allogenic [ACI (RT1^a) to LEW (RT1^l)] 2 cm epineural tubes were transplanted into sciatic nerve gaps in 3 groups without immunosupression: Group 1 the tube was filled with saline control, Group 2 supported with isogenic BMSC [LEW (RT1^l)], Group 3 allogenic BMSC [ACI (RT1^a)]. Before transplantation 3.5-4 x106 BMSC were stained with PKH-dye to evaluate engraftment of cells. 6 additional autograft repairs were performed as a control group. Assessment methods included clinical examination: pinprick (PP) and toe-spread (TS) test at 6, 12 and 24 weeks post-transplant, Somatosensory Evoked Potentials (SSEP), Gastrocnemius Muscle Index (GMI), histomorphometry, immunostaining for NGF and Laminin B2 at 24 weeks. Results Macroscopic observation revealed nerve regeneration through the tube without any signs of rejection. 6 and 12 weeks post transplantation there were no differences between experimental groups in TS and PP evaluation. At 24 weeks saline group had tendency to lower TS scores, however no differences were noted in PP. Significantly higher GMI were observed in autograft group compared to Group 1 and Group 2 compared to Group 1 and 3. There were no significant differences between groups in SSEP latencies and amplitudes. Autograft group had thicker myelin and nerve fibers than Group 1 and 2 (Figure 1). Saline group had significantly higher axonal density than autograft group and ACI BMSC group. Immunostaining confirmed presence of BMSC expressing NGF in the tube up to 24 weeks (Figure 2). Laminin B2 expression was comparable in all groups. Conclusions Allogenic epineural tube alone provides neuropermissive environment for nerve regeneration without immunosupression, however local BMSC therapy supports maturation of nerve fibers. Allogenic epineural tube supports nerve regeneration by high expression of Laminin B2. NGF expression by BMSC potentiates this effect. Allogenic epineural tube/BMSC construct may be a future alternative to autograft repair, with comparable outcomes.

Disclosure: All authors have declared no conflicts of interest.