In Vivo Survival of Mesenchymal Stromal Cell–Enhanced Decellularized Nerve Grafts for Segmental Peripheral Nerve Reconstruction

Purpose: Adipose-derived mesenchymal stromal cells (MSCs) have emerged as promising tools for peripheral nerve reconstruction. There is a paucity of information regarding the ultimate survivorship of implanted MSCs or whether these cells remain where they are placed. The aim of the present study was to track the in vivo distribution and survival of MSCs seeded on a decellularized nerve allograft reconstruction of a peripheral nerve defect using luciferase-based bioluminescence imaging (BLI). Methods: To determine the in vivo survivability of MSCs, autologous Lewis rat MSCs were stably labeled with luciferase by lentiviral particles. Labeled cells were dynamically seeded onto a Sprague Dawley decellularized rat nerve allograft and used to bridge a 10-mm sciatic nerve defect. The MSC survival was determined by performing in vivo BLI to detect living cells. Twelve animals were examined at 24 hours after implantation, 3, 7, 9, 11, and 14 days, and at daily intervals thereafter if signals were still present. Results: Labeled MSCs could be detected for up to 29 days. Gradually diminishing BLI signals were observed within the first week following implantation. Implanted MSCs were not detected anywhere other than the site of surgery. Conclusions: The MSCs seeded on decellularized nerve allografts can survive in vivo but have finite survival after implantation. There was no evidence of migration of MSCs to surrounding tissues. Clinical relevance: The findings support a therapeutic approach that combines MSCs with a biological scaffold for peripheral nerve surgery. It provides understanding of the viability and distribution of implanted MSCs, which is a prerequisite before clinical translation can be considered.