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Shin A.y. - One of the best experts on this subject based on the ideXlab platform.
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Adipose derived mesenchymal stem cells seeded onto a decellularized Nerve Allograft enhances angiogenesis in a rat sciatic Nerve defect model
'Wiley', 2020Co-Authors: Mathot F., Rbia N., Hovius S.e.r., Bishop A.t., Shin A.y.Abstract:PURPOSE: Adipose derived mesenchymal stem cells (MSCs) are hypothesized to supplement tissues with growth factors essential for regeneration and neovascularization. The purpose of this study was to determine the effect of MSCs with respect to neoangiogenesis when seeded onto a decellularized Nerve Allograft in a rat sciatic Nerve defect model. METHODS: Allograft Nerves were harvested from Sprague-Dawley rats and decellularized. MSCs were obtained from Lewis rats. 10 mm sciatic Nerve defects in Lewis rats were reconstructed with reversed autograft Nerves, decellularized Allografts, decellularized Allografts seeded with undifferentiated MSC or decellularized Allografts seeded with differentiated MSCs. At 16 weeks, the vascular surface area and volume were evaluated. RESULTS: The vascular surface area in normal Nerves (34.9 +/- 5.7%), autografts (29.5 +/- 8.7%), Allografts seeded with differentiated (38.9 +/- 7.0%) and undifferentiated MSCs (29.2 +/- 3.4%) did not significantly differ from each other. Unseeded Allografts (21.2 +/- 6.2%) had a significantly lower vascular surface area percentage than normal nonoperated Nerves (13.7%, p = .001) and Allografts seeded with differentiated MSCs (17.8%, p = .001). Although the vascular surface area was significantly correlated to the vascular volume (r = .416; p = .008), no significant differences were found between groups concerning vascular volumes. The vascularization pattern in Allografts seeded with MSCs consisted of an extensive nonaligned network of microvessels with a centripetal pattern, while the vessels in autografts and normal Nerves were more longitudinally aligned with longitudinal inosculation patterns. CONCLUSIONS: Neoangiogenesis of decellularized Allograft Nerves was enhanced by stem cell seeding, in particular by differentiated MSCs. The pattern of vascularization was different between decellularized Allograft Nerves seeded with MSCs compared to autograft Nerves
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Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed Nerve Allograft
'Elsevier BV', 2020Co-Authors: Mathot F., Rbia N., Thaler R., Wijnen, A.j. Van, Bishop A.t., Shin A.y.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
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Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed Nerve Allograft
'Elsevier BV', 2020Co-Authors: Mathot F., Rbia N., Thaler R., Wijnen, A.j. Van, Bishop A.t., Shin A.y.Abstract:Item does not contain fulltextBACKGROUND: 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
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Functional Outcome after Reconstruction of a Long Nerve Gap in Rabbits Using Optimized Decellularized Nerve Allografts
'Ovid Technologies (Wolters Kluwer Health)', 2020Co-Authors: Bulstra L.f., Hovius S.e.r., Friedrich P.f., Bishop A.t., Hundepool C.a., Shin A.y.Abstract:Item does not contain fulltextBACKGROUND: Processed Nerve Allografts are a promising alternative to Nerve autografts, providing an unlimited, readily available supply and avoiding donor-site morbidity and the need for immunosuppression. Currently, clinically available Nerve Allografts do not provide satisfactory results for motor reconstruction. This study evaluated motor recovery after reconstruction of a long Nerve gap using a processed Nerve Allograft and the influence of storage techniques. METHODS: Nerve Allografts were decellularized using elastase and detergents and stored at either 4 degrees or -80 degrees C. In 36 New Zealand White rabbits, a 3-cm peroneal Nerve gap was repaired with either an autograft (group 1, control) or a cold-stored (group 2) or frozen-stored (group 3) processed Nerve Allograft. Nerve recovery was evaluated using longitudinal ultrasound measurements, electrophysiology (compound muscle action potentials), isometric tetanic force, wet muscle weight, and histomorphometry after 24 weeks. RESULTS: Longitudinal ultrasound measurements showed that the cold-stored Allograft provided earlier regeneration than the frozen-stored Allograft. Furthermore, ultrasound showed significantly inferior recovery in group 3 than in both other groups (p < 0.05). Muscle weight and isometric tetanic force showed similar outcomes in the autograft and cold-stored Allograft groups [p = 0.096 (muscle weight) and p = 0.286 (isometric tetanic force)], and confirmed the inferiority of the frozen-stored Allograft to the autograft [p < 0.01 (muscle weight) and p = 0.02 (isometric tetanic force)]. CONCLUSIONS: Frozen storage of the Nerve Allograft significantly impairs functional recovery and should be avoided. The cold-stored optimized Nerve Allograft yields functional recovery similar to the gold standard autograft in the reconstruction of a 3-cm motor Nerve defect. Future studies should focus on further improvement of the Nerve Allograft
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Functional Outcome after Reconstruction of a Long Nerve Gap in Rabbits Using Optimized Decellularized Nerve Allografts
'Ovid Technologies (Wolters Kluwer Health)', 2020Co-Authors: Bulstra L.f., Hovius S.e.r., Friedrich P.f., Bishop A.t., Hundepool C.a., Shin A.y.Abstract:BACKGROUND: Processed Nerve Allografts are a promising alternative to Nerve autografts, providing an unlimited, readily available supply and avoiding donor-site morbidity and the need for immunosuppression. Currently, clinically available Nerve Allografts do not provide satisfactory results for motor reconstruction. This study evaluated motor recovery after reconstruction of a long Nerve gap using a processed Nerve Allograft and the influence of storage techniques. METHODS: Nerve Allografts were decellularized using elastase and detergents and stored at either 4 degrees or -80 degrees C. In 36 New Zealand White rabbits, a 3-cm peroneal Nerve gap was repaired with either an autograft (group 1, control) or a cold-stored (group 2) or frozen-stored (group 3) processed Nerve Allograft. Nerve recovery was evaluated using longitudinal ultrasound measurements, electrophysiology (compound muscle action potentials), isometric tetanic force, wet muscle weight, and histomorphometry after 24 weeks. RESULTS: Longitudinal ultrasound measurements showed that the cold-stored Allograft provided earlier regeneration than the frozen-stored Allograft. Furthermore, ultrasound showed significantly inferior recovery in group 3 than in both other groups (p < 0.05). Muscle weight and isometric tetanic force showed similar outcomes in the autograft and cold-stored Allograft groups [p = 0.096 (muscle weight) and p = 0.286 (isometric tetanic force)], and confirmed the inferiority of the frozen-stored Allograft to the autograft [p < 0.01 (muscle weight) and p = 0.02 (isometric tetanic force)]. CONCLUSIONS: Frozen storage of the Nerve Allograft significantly impairs functional recovery and should be avoided. The cold-stored optimized Nerve Allograft yields functional recovery similar to the gold standard autograft in the reconstruction of a 3-cm motor Nerve defect. Future studies should focus on further improvement of the Nerve Allograft
Susan E Mackinnon - One of the best experts on this subject based on the ideXlab platform.
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neuroma management capping Nerve injuries with an acellular Nerve Allograft can limit axon regeneration
Hand, 2021Co-Authors: Thomas Hong, Susan E Mackinnon, Ian Wood, Daniel A Hunter, Ying Yan, Matthew D Wood, Amy M MooreAbstract:Background: Management of painful neuromas continues to challenge clinicians. Controlling axon growth to prevent neuroma has gained considerable traction. A logical extension of this idea is to the...
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stem cell based approaches to enhance Nerve regeneration and improve functional outcomes in vascularized composite allotransplantation
Current Opinion in Organ Transplantation, 2018Co-Authors: Thomas H Tung, Susan E MackinnonAbstract:PURPOSE OF REVIEW The current review will discuss the current understanding of Nerve regeneration in vascularized composite allotransplantation (VCA). The success of proximal arm and leg transplants has been hampered by the limitations of Nerve regrowth across long distances resulting in poor regeneration and functional recovery. Relevant research in stem-cell therapies to overcome these issues will be reviewed. RECENT FINDINGS The effect of rejection on Nerve regeneration in the VCA may be unpredictable and may be quite different for the Nerve Allograft. The issues that limit functional outcome are likely common to both VCA and proximal Nerve injuries or replantation. Stem-cell therapies have focused on augmenting Schwann cell function and appear promising. SUMMARY A better understanding of the effects of transplant rejection on Nerve regeneration and function, as well as the factors that affect regeneration over long distances may inform further therapeutic approaches for improvement.
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acellular Nerve Allografts in peripheral Nerve regeneration a comparative study
Muscle & Nerve, 2011Co-Authors: Amy M Moore, Susan E Mackinnon, Daniel A Hunter, Wilson Z. Ray, Kristofer E. Chenard, Matthew R Macewan, Katherine B Santosa, Philip J JohnsonAbstract:Introduction: Processed Nerve Allografts offer a promising alternative to Nerve autografts in the surgical management of peripheral Nerve injuries where short deficits exist. Methods: Three established models of acellular Nerve Allograft (cold-preserved, detergent-processed, and AxoGen-processed Nerve Allografts) were compared with Nerve isografts and silicone Nerve guidance conduits in a 14-mm rat sciatic Nerve defect. Results: All acellular Nerve grafts were superior to silicone Nerve conduits in support of Nerve regeneration. Detergent-processed Allografts were similar to isografts at 6 weeks postoperatively, whereas AxoGen-processed and cold-preserved Allografts supported significantly fewer regenerating Nerve fibers. Measurement of muscle force confirmed that detergent-processed Allografts promoted isograft-equivalent levels of motor recovery 16 weeks postoperatively. All acellular Allografts promoted greater amounts of motor recovery compared with silicone conduits. Conclusion: These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular Nerve Allografts affects recovery in vivo. Muscle Nerve, 2011
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costimulation blockade inhibits the indirect pathway of allorecognition in Nerve Allograft rejection
Muscle & Nerve, 2011Co-Authors: Rahul Kasukurthi, Susan E Mackinnon, Daniel A Hunter, Philip J Johnson, Katherine B Santosa, Thalachallour Mohanakumar, Santosh S Kale, Thomas H TungAbstract:Background—Nerve Allografts provide a temporary scaffold for host Nerve regeneration. The need for systemic immunosuppression limits clinical application. Characterization of the immunological mechanisms that induce immune hyporesponsiveness may provide a basis for optimizing immunomodulating regimens. Methods—We utilized wild type and MHC class II – deficient mice, as both recipients and donors. Host treatment consisted of triple costimulatory blockade. Quantitative assessment was made at three weeks using Nerve histomorphometry, and muscle testing was performed on a subset of animals at seven weeks. Results—Nerve Allograft rejection occurred as long as either the direct or indirect pathway were functional. Indirect antigen presentation appeared to be more important. Conclusion—Nerve Allograft rejection occurs in the absence of a normal direct or indirect immune response but may be more dependent on indirect allorecognition. The indirect pathway is required to induce costimulatory blockade immune hyporesponsiveness.
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the role of t helper cell differentiation in promoting Nerve Allograft survival with costimulation blockade
Journal of Neurosurgery, 2010Co-Authors: Wilson Z. Ray, Susan E Mackinnon, Amy M Moore, Daniel A Hunter, Rahul Kasukurthi, Esther M Papp, Andrew Yee, Nancy L Solowski, Thalachallour Mohanakumar, Thomas H TungAbstract:Object Peripheral Nerve Allografts provide a temporary scaffold for host Nerve regeneration and allow for the repair of significant segmental Nerve injuries. Despite this potential, Nerve Allograft transplantation requires temporary systemic immunosuppression. Characterization of the immunological mechanisms involved in the induction of immune hyporesponsiveness to prevent Nerve Allograft rejection will help provide a basis for optimizing immunomodulation regimens or manipulating donor Nerve Allografts to minimize or eliminate the need for global immunosuppression. Methods The authors used C57Bl/6 mice and STAT4 and STAT6 gene BALB/c knockout mice. A nonvascularized Nerve Allograft was used to reconstruct a 1-cm sciatic Nerve gap in the murine model. A triple costimulatory blockade of the CD40, CD28/B7, and inducible costimulatory (ICOS) pathways was used. Quantitative assessment was performed at 3 weeks with Nerve histomorphometry, walking track analysis, and the enzyme-linked immunospot assay. Results T...
Bishop A.t. - One of the best experts on this subject based on the ideXlab platform.
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Gene expression and growth factor analysis in early Nerve regeneration following segmental Nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized Nerve Allograft
2020Co-Authors: Rbia N., Bulstra L.f., Friedrich P.f., Bishop A.t., Nijhuis T.h.j., Shin, A.y. Y.)Abstract:Abstract Background: The purpose of this study was to evaluate the molecular mechanisms underlying Nerve repair by a decellularized Nerve Allograft seeded with adipose-derived mesenchymal stromal cells (MSCs) and compare it to the unseeded Allograft and autograft Nerve. Methods: Undifferentiated MSCs were seeded onto decellularized Nerve Allografts and used to reconstruct a 10 mm gap in a rat sciatic Nerve model. Gene expression profiles of genes essential for Nerve regeneration and immunohistochemical staining (IHC) for PGP9.5, NGF, RECA-1, and S100 were obtained 2 weeks postoperatively. Results: Semi-quantitative RT-PCR analysis showed that the angiogenic molecule VEGFA was significantly increased in seeded Allografts, and transcription factor SOX2 was downregulated in seeded Allografts. Seeded grafts showed a significant increase in immunohistochemical markers NGF and RECA-1, when compared with unseeded Allografts. Conclusions: MSCs contributed to the secretion of trophic factors. A beneficial effect of the MSCs on angiogenesis was found when compared with the unseeded Nerve Allograft, but implanted MSCs did not show evidence of differentiation into Schwann cell-like cells
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Gene expression and growth factor analysis in early Nerve regeneration following segmental Nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized Nerve Allograft
'Ovid Technologies (Wolters Kluwer Health)', 2020Co-Authors: Rbia N., Bulstra L.f., Bishop A.t., Nijhuis T.h.j., Friedrich P. F., Shin, A.y. Y.)Abstract:Background: The purpose of this study was to evaluate the molecular mechanisms underlying Nerve repair by a decellularized Nerve Allograft seeded with adiposederived mesenchymal stromal cells (MSCs) and compare it to the unseeded Allograft and autograft Nerve. Methods: Undifferentiated MSCs were seeded onto decellularized Nerve Allografts and used to reconstruct a 10mm gap in a rat sciatic Nerve model. Gene expression profi
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Adipose derived mesenchymal stem cells seeded onto a decellularized Nerve Allograft enhances angiogenesis in a rat sciatic Nerve defect model
'Wiley', 2020Co-Authors: Mathot F., Rbia N., Hovius S.e.r., Bishop A.t., Shin A.y.Abstract:PURPOSE: Adipose derived mesenchymal stem cells (MSCs) are hypothesized to supplement tissues with growth factors essential for regeneration and neovascularization. The purpose of this study was to determine the effect of MSCs with respect to neoangiogenesis when seeded onto a decellularized Nerve Allograft in a rat sciatic Nerve defect model. METHODS: Allograft Nerves were harvested from Sprague-Dawley rats and decellularized. MSCs were obtained from Lewis rats. 10 mm sciatic Nerve defects in Lewis rats were reconstructed with reversed autograft Nerves, decellularized Allografts, decellularized Allografts seeded with undifferentiated MSC or decellularized Allografts seeded with differentiated MSCs. At 16 weeks, the vascular surface area and volume were evaluated. RESULTS: The vascular surface area in normal Nerves (34.9 +/- 5.7%), autografts (29.5 +/- 8.7%), Allografts seeded with differentiated (38.9 +/- 7.0%) and undifferentiated MSCs (29.2 +/- 3.4%) did not significantly differ from each other. Unseeded Allografts (21.2 +/- 6.2%) had a significantly lower vascular surface area percentage than normal nonoperated Nerves (13.7%, p = .001) and Allografts seeded with differentiated MSCs (17.8%, p = .001). Although the vascular surface area was significantly correlated to the vascular volume (r = .416; p = .008), no significant differences were found between groups concerning vascular volumes. The vascularization pattern in Allografts seeded with MSCs consisted of an extensive nonaligned network of microvessels with a centripetal pattern, while the vessels in autografts and normal Nerves were more longitudinally aligned with longitudinal inosculation patterns. CONCLUSIONS: Neoangiogenesis of decellularized Allograft Nerves was enhanced by stem cell seeding, in particular by differentiated MSCs. The pattern of vascularization was different between decellularized Allograft Nerves seeded with MSCs compared to autograft Nerves
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Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed Nerve Allograft
'Elsevier BV', 2020Co-Authors: Mathot F., Rbia N., Thaler R., Wijnen, A.j. Van, Bishop A.t., Shin A.y.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
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Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed Nerve Allograft
'Elsevier BV', 2020Co-Authors: Mathot F., Rbia N., Thaler R., Wijnen, A.j. Van, Bishop A.t., Shin A.y.Abstract:Item does not contain fulltextBACKGROUND: 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
Rbia N. - One of the best experts on this subject based on the ideXlab platform.
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Gene expression and growth factor analysis in early Nerve regeneration following segmental Nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized Nerve Allograft
2020Co-Authors: Rbia N., Bulstra L.f., Friedrich P.f., Bishop A.t., Nijhuis T.h.j., Shin, A.y. Y.)Abstract:Abstract Background: The purpose of this study was to evaluate the molecular mechanisms underlying Nerve repair by a decellularized Nerve Allograft seeded with adipose-derived mesenchymal stromal cells (MSCs) and compare it to the unseeded Allograft and autograft Nerve. Methods: Undifferentiated MSCs were seeded onto decellularized Nerve Allografts and used to reconstruct a 10 mm gap in a rat sciatic Nerve model. Gene expression profiles of genes essential for Nerve regeneration and immunohistochemical staining (IHC) for PGP9.5, NGF, RECA-1, and S100 were obtained 2 weeks postoperatively. Results: Semi-quantitative RT-PCR analysis showed that the angiogenic molecule VEGFA was significantly increased in seeded Allografts, and transcription factor SOX2 was downregulated in seeded Allografts. Seeded grafts showed a significant increase in immunohistochemical markers NGF and RECA-1, when compared with unseeded Allografts. Conclusions: MSCs contributed to the secretion of trophic factors. A beneficial effect of the MSCs on angiogenesis was found when compared with the unseeded Nerve Allograft, but implanted MSCs did not show evidence of differentiation into Schwann cell-like cells
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Gene expression and growth factor analysis in early Nerve regeneration following segmental Nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized Nerve Allograft
'Ovid Technologies (Wolters Kluwer Health)', 2020Co-Authors: Rbia N., Bulstra L.f., Bishop A.t., Nijhuis T.h.j., Friedrich P. F., Shin, A.y. Y.)Abstract:Background: The purpose of this study was to evaluate the molecular mechanisms underlying Nerve repair by a decellularized Nerve Allograft seeded with adiposederived mesenchymal stromal cells (MSCs) and compare it to the unseeded Allograft and autograft Nerve. Methods: Undifferentiated MSCs were seeded onto decellularized Nerve Allografts and used to reconstruct a 10mm gap in a rat sciatic Nerve model. Gene expression profi
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Adipose derived mesenchymal stem cells seeded onto a decellularized Nerve Allograft enhances angiogenesis in a rat sciatic Nerve defect model
'Wiley', 2020Co-Authors: Mathot F., Rbia N., Hovius S.e.r., Bishop A.t., Shin A.y.Abstract:PURPOSE: Adipose derived mesenchymal stem cells (MSCs) are hypothesized to supplement tissues with growth factors essential for regeneration and neovascularization. The purpose of this study was to determine the effect of MSCs with respect to neoangiogenesis when seeded onto a decellularized Nerve Allograft in a rat sciatic Nerve defect model. METHODS: Allograft Nerves were harvested from Sprague-Dawley rats and decellularized. MSCs were obtained from Lewis rats. 10 mm sciatic Nerve defects in Lewis rats were reconstructed with reversed autograft Nerves, decellularized Allografts, decellularized Allografts seeded with undifferentiated MSC or decellularized Allografts seeded with differentiated MSCs. At 16 weeks, the vascular surface area and volume were evaluated. RESULTS: The vascular surface area in normal Nerves (34.9 +/- 5.7%), autografts (29.5 +/- 8.7%), Allografts seeded with differentiated (38.9 +/- 7.0%) and undifferentiated MSCs (29.2 +/- 3.4%) did not significantly differ from each other. Unseeded Allografts (21.2 +/- 6.2%) had a significantly lower vascular surface area percentage than normal nonoperated Nerves (13.7%, p = .001) and Allografts seeded with differentiated MSCs (17.8%, p = .001). Although the vascular surface area was significantly correlated to the vascular volume (r = .416; p = .008), no significant differences were found between groups concerning vascular volumes. The vascularization pattern in Allografts seeded with MSCs consisted of an extensive nonaligned network of microvessels with a centripetal pattern, while the vessels in autografts and normal Nerves were more longitudinally aligned with longitudinal inosculation patterns. CONCLUSIONS: Neoangiogenesis of decellularized Allograft Nerves was enhanced by stem cell seeding, in particular by differentiated MSCs. The pattern of vascularization was different between decellularized Allograft Nerves seeded with MSCs compared to autograft Nerves
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Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed Nerve Allograft
'Elsevier BV', 2020Co-Authors: Mathot F., Rbia N., Thaler R., Wijnen, A.j. Van, Bishop A.t., Shin A.y.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
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Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed Nerve Allograft
'Elsevier BV', 2020Co-Authors: Mathot F., Rbia N., Thaler R., Wijnen, A.j. Van, Bishop A.t., Shin A.y.Abstract:Item does not contain fulltextBACKGROUND: 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
Amy M Moore - One of the best experts on this subject based on the ideXlab platform.
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neuroma management capping Nerve injuries with an acellular Nerve Allograft can limit axon regeneration
Hand, 2021Co-Authors: Thomas Hong, Susan E Mackinnon, Ian Wood, Daniel A Hunter, Ying Yan, Matthew D Wood, Amy M MooreAbstract:Background: Management of painful neuromas continues to challenge clinicians. Controlling axon growth to prevent neuroma has gained considerable traction. A logical extension of this idea is to the...
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acellular Nerve Allografts in peripheral Nerve regeneration a comparative study
Muscle & Nerve, 2011Co-Authors: Amy M Moore, Susan E Mackinnon, Daniel A Hunter, Wilson Z. Ray, Kristofer E. Chenard, Matthew R Macewan, Katherine B Santosa, Philip J JohnsonAbstract:Introduction: Processed Nerve Allografts offer a promising alternative to Nerve autografts in the surgical management of peripheral Nerve injuries where short deficits exist. Methods: Three established models of acellular Nerve Allograft (cold-preserved, detergent-processed, and AxoGen-processed Nerve Allografts) were compared with Nerve isografts and silicone Nerve guidance conduits in a 14-mm rat sciatic Nerve defect. Results: All acellular Nerve grafts were superior to silicone Nerve conduits in support of Nerve regeneration. Detergent-processed Allografts were similar to isografts at 6 weeks postoperatively, whereas AxoGen-processed and cold-preserved Allografts supported significantly fewer regenerating Nerve fibers. Measurement of muscle force confirmed that detergent-processed Allografts promoted isograft-equivalent levels of motor recovery 16 weeks postoperatively. All acellular Allografts promoted greater amounts of motor recovery compared with silicone conduits. Conclusion: These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular Nerve Allografts affects recovery in vivo. Muscle Nerve, 2011
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the role of t helper cell differentiation in promoting Nerve Allograft survival with costimulation blockade
Journal of Neurosurgery, 2010Co-Authors: Wilson Z. Ray, Susan E Mackinnon, Amy M Moore, Daniel A Hunter, Rahul Kasukurthi, Esther M Papp, Andrew Yee, Nancy L Solowski, Thalachallour Mohanakumar, Thomas H TungAbstract:Object Peripheral Nerve Allografts provide a temporary scaffold for host Nerve regeneration and allow for the repair of significant segmental Nerve injuries. Despite this potential, Nerve Allograft transplantation requires temporary systemic immunosuppression. Characterization of the immunological mechanisms involved in the induction of immune hyporesponsiveness to prevent Nerve Allograft rejection will help provide a basis for optimizing immunomodulation regimens or manipulating donor Nerve Allografts to minimize or eliminate the need for global immunosuppression. Methods The authors used C57Bl/6 mice and STAT4 and STAT6 gene BALB/c knockout mice. A nonvascularized Nerve Allograft was used to reconstruct a 1-cm sciatic Nerve gap in the murine model. A triple costimulatory blockade of the CD40, CD28/B7, and inducible costimulatory (ICOS) pathways was used. Quantitative assessment was performed at 3 weeks with Nerve histomorphometry, walking track analysis, and the enzyme-linked immunospot assay. Results T...
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Nerve Allotransplantation as it Pertains to Composite Tissue Transplantation
HAND, 2009Co-Authors: Amy M Moore, Wilson Z. Ray, Kristofer E. Chenard, Thomas Tung, Susan E MackinnonAbstract:Nerve Allografts provide a temporary scaffold for host Nerve regeneration and allow for the repair of significant segmental Nerve injuries. From rodent, large animal, and nonhuman primate studies, as well as clinical experience, Nerve Allografts, with the use of immunosuppression, have the capacity to provide equal regeneration and function to that of an autograft. In contrast to solid organ transplantation and composite tissue transfers, Nerve Allograft transplantation requires only temporary immunosuppression. Furthermore, Nerve Allograft rejection is difficult to assess, as the Nerves are surgically buried and are without an immediate functional endpoint to monitor. In this article, we review what we know about peripheral Nerve Allograft transplantation from three decades of experience and apply our current understanding of Nerve regeneration to the emerging field of composite tissue transplantation.
