Femke Mathot1, Nadia Rbia2, Roman Thaler3, Allen T Bishop4, Andre J Van Wijnen5, Alexander Y Shin6. 1. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; Department of Plastic Surgery, Radboudumc, Nijmegen, The Netherlands. 2. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; Department of Plastic, Reconstructive and Hand Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. 3. Department of Biochemistry and Molecular Biology, Mayo Clinic, MN, USA. 4. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA. 5. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, MN, USA. Electronic address: vanwijnen.andre@mayo.edu. 6. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA. Electronic address: shin.alexander@mayo.edu.
Abstract
BACKGROUND: Differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells onto processed nerve allografts may support peripheral nerve repair. The purpose of this study was to understand the biological characteristics of undifferentiated and differentiated MSCs before and after seeding onto a processed nerve allograft by comparing gene expression profiles. METHODS: MSCs from Lewis rats were cultured in maintenance media or differentiated into Schwann-like cells. Both treatment groups were dynamically seeded onto decellularized nerve allografts derived from Sprague-Dawley rats. Gene expression was quantified by quantitative polymerase chain reaction (qPCR) analysis of representative biomarkers, including neurotrophic (GDNF, PTN, GAP43, PMP22), angiogenic (CD31, VEGF1), extracellular matrix (ECM) (COL1A1, COL3A1, FBLN1, LAMB2) or cell cycle (CAPS3, CCBN2) genes. Gene expression values were statistically evaluated using a 2-factor ANOVA with repeated measures. RESULTS: Baseline gene expression of undifferentiated and differentiated MSCs was significantly altered upon interaction with processed nerve allografts. Interaction between processed allografts and undifferentiated MSCs enhanced expression of neurotrophic (NGF, GDNF, PMP22), ECM (FBLN1, LAMB2) and regulatory cell cycle genes (CCNB2) during a 7-day time course. Interactions of differentiated MSCs with nerve allografts enhanced expression of neurotrophic (NGF, GDNF, GAP43), angiogenic (VEGF1), ECM (FBLN1) and regulatory cell cycle genes (CASP3, CCNB2) within one week. CONCLUSIONS: Dynamic seeding onto processed nerve allografts modulates temporal gene expression profiles of differentiated and undifferentiated MSCs. These changes in gene expressions may support the reparative functions of MSCs in supporting nerve regeneration in different stages of axonal growth.
BACKGROUND: Differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells onto processed nerve allografts may support peripheral nerve repair. The purpose of this study was to understand the biological characteristics of undifferentiated and differentiated MSCs before and after seeding onto a processed nerve allograft by comparing gene expression profiles. METHODS: MSCs from Lewis rats were cultured in maintenance media or differentiated into Schwann-like cells. Both treatment groups were dynamically seeded onto decellularized nerve allografts derived from Sprague-Dawley rats. Gene expression was quantified by quantitative polymerase chain reaction (qPCR) analysis of representative biomarkers, including neurotrophic (GDNF, PTN, GAP43, PMP22), angiogenic (CD31, VEGF1), extracellular matrix (ECM) (COL1A1, COL3A1, FBLN1, LAMB2) or cell cycle (CAPS3, CCBN2) genes. Gene expression values were statistically evaluated using a 2-factor ANOVA with repeated measures. RESULTS: Baseline gene expression of undifferentiated and differentiated MSCs was significantly altered upon interaction with processed nerve allografts. Interaction between processed allografts and undifferentiated MSCs enhanced expression of neurotrophic (NGF, GDNF, PMP22), ECM (FBLN1, LAMB2) and regulatory cell cycle genes (CCNB2) during a 7-day time course. Interactions of differentiated MSCs with nerve allografts enhanced expression of neurotrophic (NGF, GDNF, GAP43), angiogenic (VEGF1), ECM (FBLN1) and regulatory cell cycle genes (CASP3, CCNB2) within one week. CONCLUSIONS: Dynamic seeding onto processed nerve allografts modulates temporal gene expression profiles of differentiated and undifferentiated MSCs. These changes in gene expressions may support the reparative functions of MSCs in supporting nerve regeneration in different stages of axonal growth.
Authors: Tiam M Saffari; Amr Badreldin; Femke Mathot; Leila Bagheri; Allen T Bishop; Andre J van Wijnen; Alexander Y Shin Journal: Gene Date: 2020-04-27 Impact factor: 3.688
Authors: Sara Saffari; Tiam M Saffari; Katelyn Chan; Gregory H Borschel; Alexander Y Shin Journal: Biotechnol Bioeng Date: 2021-08-25 Impact factor: 4.530
Authors: Meiwand Bedar; Sofia Jerez; Nicholas Pulos; Andre J van Wijnen; Alexander Y Shin Journal: J Plast Reconstr Aesthet Surg Date: 2022-04-22 Impact factor: 3.022
Authors: Femke Mathot; Tiam M Saffari; Nadia Rbia; Tim H J Nijhuis; Allen T Bishop; Steven E R Hovius; Alexander Y Shin Journal: Plast Reconstr Surg Date: 2021-08-01 Impact factor: 5.169
Authors: T M Saffari; F Mathot; R Thaler; A J van Wijnen; A T Bishop; A Y Shin Journal: J Plast Reconstr Aesthet Surg Date: 2020-12-24 Impact factor: 3.022