Sara Saffari1,2, Tiam M Saffari1,2, Katelyn Chan3,4, Gregory H Borschel3,4,5,6,7, Alexander Y Shin1. 1. Division of Hand and Microvascular Surgery, Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA. 2. Department of Plastic-, Reconstructive- and Hand Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. 3. Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. Department of Engineering, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. 5. Division of Neurosciences and Mental Health, SickKids Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada. 6. Division of Plastic & Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. 7. Division of Plastic Surgery, Indiana University and Riley Hospital for Children, Indianapolis, Indiana, USA.
Abstract
BACKGROUND: The aim of this study was to investigate the combined effect of mesenchymal stem cells (MSC) and local delivery of tacrolimus (FK506) on nerve regeneration when applied to nerve autografts and decellularized allografts. METHODS: A three-dimensional in vitro compartmented cell culture system consisting of a neonatal dorsal root ganglion adjacent to a nerve graft was used to evaluate the regenerating neurites into the peripheral nerve scaffold. Nerve autografts and allografts were treated with (i) undifferentiated MSCs, (ii) FK506 (100 ng/mL) or (iii) both (N = 9/group). After 48 hours, neurite extension was measured to quantify nerve regeneration and stem cell viability was evaluated. RESULTS: Stem cell viability was confirmed in all MSC-treated grafts. Neurite extension was superior in autografts treated with FK506, and MSCs and FK506 combined (p < 0.001 and p = 0.0001, respectively), and autografts treated with MSCs (p = 0.12) were comparable to untreated autografts. In allografts, FK506 treatment and combined treatment were superior to controls (p < 0.001 and p = 0.0001, respectively), and treatment with MSCs (p = 0.09) was comparable to controls. All autograft groups were superior compared to their respective allograft treatment group (p < 0.05) in neurite extension. CONCLUSIONS: Alone, either MSC or FK506 treatment improved neurite outgrowth, and combined they further enhanced neurite extension in both autografts and allografts.
BACKGROUND: The aim of this study was to investigate the combined effect of mesenchymal stem cells (MSC) and local delivery of tacrolimus (FK506) on nerve regeneration when applied to nerve autografts and decellularized allografts. METHODS: A three-dimensional in vitro compartmented cell culture system consisting of a neonatal dorsal root ganglion adjacent to a nerve graft was used to evaluate the regenerating neurites into the peripheral nerve scaffold. Nerve autografts and allografts were treated with (i) undifferentiated MSCs, (ii) FK506 (100 ng/mL) or (iii) both (N = 9/group). After 48 hours, neurite extension was measured to quantify nerve regeneration and stem cell viability was evaluated. RESULTS: Stem cell viability was confirmed in all MSC-treated grafts. Neurite extension was superior in autografts treated with FK506, and MSCs and FK506 combined (p < 0.001 and p = 0.0001, respectively), and autografts treated with MSCs (p = 0.12) were comparable to untreated autografts. In allografts, FK506 treatment and combined treatment were superior to controls (p < 0.001 and p = 0.0001, respectively), and treatment with MSCs (p = 0.09) was comparable to controls. All autograft groups were superior compared to their respective allograft treatment group (p < 0.05) in neurite extension. CONCLUSIONS: Alone, either MSC or FK506 treatment improved neurite outgrowth, and combined they further enhanced neurite extension in both autografts and allografts.
Authors: Henrik Ekberg; Helio Tedesco-Silva; Alper Demirbas; Stefan Vítko; Björn Nashan; Alp Gürkan; Raimund Margreiter; Christian Hugo; Josep M Grinyó; Ulrich Frei; Yves Vanrenterghem; Pierre Daloze; Philip F Halloran Journal: N Engl J Med Date: 2007-12-20 Impact factor: 91.245
Authors: Tiam M Saffari; Katelyn Chan; Sara Saffari; Kevin J Zuo; Renee M McGovern; Joel M Reid; Gregory H Borschel; Alexander Y Shin Journal: Biotechnol Bioeng Date: 2021-05-03 Impact factor: 4.530