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Artikel ; Online: The Role of Nerve Graft Substitutes in Motor and Mixed Motor/Sensory Peripheral Nerve Injuries.

Rbia, Nadia / Shin, Alexander Y

2017 Band 42, Heft 5, Seite(n) 367–377

Abstract: Alternatives to nerve autograft have been invented and approved for clinical use. The reported outcomes of these alternatives in mixed motor nerve repair in humans are scarce and marked by wide variabilities. The purpose of our Current Concepts review is ...

Abstract	Alternatives to nerve autograft have been invented and approved for clinical use. The reported outcomes of these alternatives in mixed motor nerve repair in humans are scarce and marked by wide variabilities. The purpose of our Current Concepts review is to provide an evidence-based overview of the effectiveness of nerve conduits and allografts in motor and mixed sensory/motor nerve reconstruction. Nerve graft substitutes have good outcomes in mixed/motor nerves in gaps less than 6 mm and internal diameters between 3 and 7 mm. There is insufficient evidence for their use in larger-gap and -diameter nerves; the evidence remains that major segmental motor or mixed nerve injury is optimally treated with a cabled nerve autograft.
Sprache	Englisch
Erscheinungsdatum	2017-05
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ZDB-ID	605716-0
ISSN	1531-6564 ; 0363-5023
ISSN (online)	1531-6564
ISSN	0363-5023
DOI	10.1016/j.jhsa.2017.02.017
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Adipose derived mesenchymal stem cells seeded onto a decellularized nerve allograft enhances angiogenesis in a rat sciatic nerve defect model.

Mathot, Femke / Rbia, Nadia / Bishop, Allen T / Hovius, Steven E R / Shin, Alexander Y

Microsurgery

2020 Band 40, Heft 5, Seite(n) 585–592

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 ... ...

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.
Mesh-Begriff(e)	Allografts ; Animals ; Mesenchymal Stem Cells ; Nerve Regeneration ; Rats ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Sciatic Nerve/surgery
Sprache	Englisch
Erscheinungsdatum	2020-03-31
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	605524-2
ISSN	1098-2752 ; 0738-1085
ISSN (online)	1098-2752
ISSN	0738-1085
DOI	10.1002/micr.30579
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed nerve allograft

Mathot, Femke / Rbia, Nadia / Thaler, Roman / Bishop, Allen T / Van Wijnen, Andre J / Shin, Alexander Y

Gene. 2020 Jan. 15, v. 724

2020

Abstract: 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 ... ...

Abstract	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.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.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.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.
Schlagwörter	allografting ; biomarkers ; cell cycle ; extracellular matrix ; gene expression ; genes ; mesenchymal stromal cells ; nerve regeneration ; nerve tissue ; quantitative polymerase chain reaction ; rats ; sowing
Sprache	Englisch
Erscheinungsverlauf	2020-0115
Erscheinungsort	Elsevier B.V.
Dokumenttyp	Artikel
Anmerkung	NAL-light
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2019.144151
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel: Gene expression profiles of human adipose-derived mesenchymal stem cells dynamically seeded on clinically available processed nerve allografts and collagen nerve guides.

Mathot, Femke / Rbia, Nadia / Thaler, Roman / Dietz, Allan B / van Wijnen, Andre J / Bishop, Allen T / Shin, Alexander Y

Neural regeneration research

2021 Band 16, Heft 8, Seite(n) 1613–1621

Abstract: It was hypothesized that mesenchymal stem cells (MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance® Nerve ... ...

Abstract	It was hypothesized that mesenchymal stem cells (MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance® Nerve Grafts or NeuraGen® Nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance® Nerve Grafts and 30 NeuraGen® Nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), pleiotrophin (PTN), growth associated protein 43 (GAP43) and brain-derived neurotrophic factor (BDNF)], myelination [peripheral myelin protein 22 (PMP22) and myelin protein zero (MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1 (PECAM1/CD31) and vascular endothelial cell growth factor alpha (VEGFA)], extracellular matrix (ECM) [collagen type alpha I (COL1A1), collagen type alpha III (COL3A1), Fibulin 1 (FBLN1) and laminin subunit beta 2 (LAMB2)] and cell surface marker cluster of differentiation 96 (CD96) gene expression was quantified. Unseeded Avance® Nerve Grafts and NeuraGen® Nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance® Nerve Grafts led to a short-term upregulation of neurotrophic (NGF, GDNF and BDNF), myelination (PMP22 and MPZ) and angiogenic genes (CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the NeuraGen® Nerve Guide led to short term upregulation of neurotrophic (NGF, GDNF and BDNF) myelination (PMP22 and MPZ), angiogenic (CD31 and VEGFA), ECM (COL1A1) and cell surface (CD96) genes and long-term upregulation of neurotrophic (GDNF and BDNF), angiogenic (CD31 and VEGFA), ECM genes (COL1A1, COL3A1, and FBLN1) and cell surface (CD96) genes. Analysis demonstrated MSCs seeded onto NeuraGen® Nerve Guides expressed significantly higher levels of neurotrophic (PTN), angiogenic (VEGFA) and ECM (COL3A1, FBLN1) genes in the long term period compared to MSCs seeded onto Avance® Nerve Grafts. Overall, the interaction between human MSCs and both nerve graft substitutes resulted in a significant upregulation of the expression of numerous genes important for nerve regeneration over time. The in vitro interaction of MSCs with the NeuraGen® Nerve Guide was more pronounced, particularly in the long term period (> 14 days after seeding). These results suggest that MSC-seeding has potential to be applied in a clinical setting, which needs to be confirmed in future in vitro and in vivo research.
Sprache	Englisch
Erscheinungsdatum	2021-01-11
Erscheinungsland	India
Dokumenttyp	Journal Article
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.303031
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Functional Outcomes of Nerve Allografts Seeded with Undifferentiated and Differentiated Mesenchymal Stem Cells in a Rat Sciatic Nerve Defect Model.

Mathot, Femke / Saffari, Tiam M / Rbia, Nadia / Nijhuis, Tim H J / Bishop, Allen T / Hovius, Steven E R / Shin, Alexander Y

Plastic and reconstructive surgery

2021 Band 148, Heft 2, Seite(n) 354–365

Abstract: Background: Mesenchymal stem cells have the potential to produce neurotrophic growth factors and establish a supportive microenvironment for neural regeneration. The purpose of this study was to determine the effect of undifferentiated and ... ...

Abstract	Background: Mesenchymal stem cells have the potential to produce neurotrophic growth factors and establish a supportive microenvironment for neural regeneration. The purpose of this study was to determine the effect of undifferentiated and differentiated mesenchymal stem cells dynamically seeded onto decellularized nerve allografts on functional outcomes when used in peripheral nerve repair. Methods: In 80 Lewis rats, a 10-mm sciatic nerve defect was reconstructed with (1) autograft, (2) decellularized allograft, (3) decellularized allograft seeded with undifferentiated mesenchymal stem cells, or (4) decellularized allograft seeded with mesenchymal stem cells differentiated into Schwann cell-like cells. Nerve regeneration was evaluated over time by cross-sectional tibial muscle ultrasound measurements, and at 12 and 16 weeks by isometric tetanic force measurements, compound muscle action potentials, muscle mass, histology, and immunofluorescence analyses. Results: At 12 weeks, undifferentiated mesenchymal stem cells significantly improved isometric tetanic force measurement and compound muscle action potential outcomes compared to decellularized allograft alone, whereas differentiated mesenchymal stem cells significantly improved compound muscle action potential outcomes. The autografts outperformed both stem cell groups histologically at 12 weeks. At 16 weeks, functional outcomes normalized between groups. At both time points, the effect of undifferentiated versus differentiated mesenchymal stem cells was not significantly different. Conclusions: Undifferentiated and differentiated mesenchymal stem cells significantly improved functional outcomes of decellularized allografts at 12 weeks and were similar to autograft results in the majority of measurements. At 16 weeks, outcomes normalized as expected. Although differences between both cell types were not statistically significant, undifferentiated mesenchymal stem cells improved functional outcomes of decellularized nerve allografts to a greater extent and had practical benefits for clinical translation by limiting preparation time and costs.
Mesh-Begriff(e)	Allografts/physiology ; Allografts/transplantation ; Animals ; Autografts/physiology ; Autografts/transplantation ; Cell Differentiation ; Disease Models, Animal ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/physiology ; Nerve Regeneration ; Nerve Transfer/methods ; Rats ; Schwann Cells/physiology ; Schwann Cells/transplantation ; Sciatic Nerve/injuries ; Sciatic Nerve/physiology ; Sciatic Nerve/transplantation ; Sciatic Neuropathy/surgery ; Transplantation, Autologous/methods ; Transplantation, Homologous/methods ; Treatment Outcome
Sprache	Englisch
Erscheinungsdatum	2021-06-18
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	208012-6
ISSN	1529-4242 ; 0032-1052 ; 0096-8501
ISSN (online)	1529-4242
ISSN	0032-1052 ; 0096-8501
DOI	10.1097/PRS.0000000000008191
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Collagen Nerve Conduits and Processed Nerve Allografts for the Reconstruction of Digital Nerve Gaps: A Single-Institution Case Series and Review of the Literature.

Rbia, Nadia / Bulstra, Liselotte F / Saffari, Tiam M / Hovius, Steven E R / Shin, Alexander Y

World neurosurgery

2019 Band 127, Seite(n) e1176–e1184

Abstract: Objective: A single-institution case series is reported and a review of the literature on the outcomes of digital nerve gap reconstruction with the NeuraGen type 1 collagen nerve conduit (Integra Life Sciences, Plainsboro New Jersey, USA) and the Avance ...

Abstract	Objective: A single-institution case series is reported and a review of the literature on the outcomes of digital nerve gap reconstruction with the NeuraGen type 1 collagen nerve conduit (Integra Life Sciences, Plainsboro New Jersey, USA) and the Avance Nerve Graft (Axogen Inc., Alachua, Florida, USA) is presented. Methods: Thirty-seven patients were included with a minimal follow-up of 12 months. Primary outcome was postoperative sensory recovery measured by static 2-point discrimination test or the Semmes-Weinstein monofilament test. Secondary outcome measurements were perioperative or postoperative complications. Final outcome data were stratified to grade results as excellent, good, or poor. Results: The mean nerve gap length was 14 ± 4.9 mm for the collagen conduits versus 18.4 ± 9.3 for nerve allografts. After 12 months, outcomes were graded as excellent sensory recovery in 48% of the collagen conduit repairs and 39% of the nerve allografts (P = 0.608), good in 26% of the conduits and 55% of the allografts (P = 0.074), and poor in 26% of the conduits versus 6% of the allografts (P = 0.091). One neuroma and 1 infection were reported. Graft rejection or extrusion was not observed. Conclusions: Nerve conduits and processed nerve allografts offer convenient off-the-shelf options for digital nerve gap repair. Both techniques offer effective means of reconstructing a digital nerve gap <2.5 cm at a minimum of 12 months of follow-up. Future prospective randomized large sample size studies comparing nerve conduits with allografts are needed to perform subgroup analyses and to define their exact role in digital nerve injuries.
Mesh-Begriff(e)	Adolescent ; Adult ; Aged ; Allografts/transplantation ; Animals ; Cattle ; Child ; Collagen/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Peripheral Nerve Injuries/diagnosis ; Peripheral Nerve Injuries/surgery ; Peripheral Nerves/transplantation ; Reconstructive Surgical Procedures/methods ; Retrospective Studies ; Young Adult
Chemische Substanzen	Collagen (9007-34-5)
Sprache	Englisch
Erscheinungsdatum	2019-04-16
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2019.04.087
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Gene expression and growth factor analysis in early nerve regeneration following segmental nerve defect reconstruction with a mesenchymal stromal cell-enhanced decellularized nerve allograft.

Rbia, Nadia / Bulstra, Liselotte F / Friedrich, Patricia F / Bishop, Allen T / Nijhuis, Tim H J / Shin, Alexander Y

Plastic and reconstructive surgery. Global open

2020 Band 8, Heft 1, Seite(n) e2579

Abstract: 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.: ... ...

Abstract	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 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.
Sprache	Englisch
Erscheinungsdatum	2020-01-21
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2851682-5
ISSN	2169-7574 ; 2169-7574
ISSN (online)	2169-7574
ISSN	2169-7574
DOI	10.1097/GOX.0000000000002579
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Introducing human adipose-derived mesenchymal stem cells to Avance

Mathot, Femke / Rbia, Nadia / Thaler, Roman / Bishop, Allen T / van Wijnen, Andre J / Shin, Alexander Y

Journal of plastic, reconstructive & aesthetic surgery : JPRAS

2020 Band 73, Heft 8, Seite(n) 1473–1481

Abstract: Background: When direct nerve coaptation is impossible after peripheral nerve injury, autografts, processed allografts, or conduits are used to bridge the nerve gap. The purpose of this study was to examine if human adipose-derived Mesenchymal Stromal/ ... ...

Abstract	Background: When direct nerve coaptation is impossible after peripheral nerve injury, autografts, processed allografts, or conduits are used to bridge the nerve gap. The purpose of this study was to examine if human adipose-derived Mesenchymal Stromal/Stem Cells (MSCs) could be introduced to commercially available nerve graft substitutes and to determine cell distribution and the seeding efficiency of a dynamic seeding strategy. Methods: MTS assays examined the viability of human MSCs after introduction to the Avance Results: The viability of MSCs was not affected by nerve substitutes. Dynamic seeding led to uniformly distributed MSCs over the surface of both nerve substitutes and revealed MSCs on the inner surface of the NeuraGen Conclusion: Human MSCs can be dynamically seeded on Avance
Mesh-Begriff(e)	Adipose Tissue/cytology ; Allografts ; Biocompatible Materials ; Cell Movement ; Cell Survival ; Collagen ; Humans ; Mesenchymal Stem Cell Transplantation ; Nerve Regeneration/physiology ; Neurosurgical Procedures/methods ; Peripheral Nerve Injuries/surgery ; Peripheral Nerves/transplantation ; Surface Properties ; Transplantation, Homologous
Chemische Substanzen	Biocompatible Materials ; Collagen (9007-34-5)
Sprache	Englisch
Erscheinungsdatum	2020-04-11
Erscheinungsland	Netherlands
Dokumenttyp	Journal Article
ZDB-ID	2217750-4
ISSN	1878-0539 ; 1748-6815 ; 0007-1226
ISSN (online)	1878-0539
ISSN	1748-6815 ; 0007-1226
DOI	10.1016/j.bjps.2020.03.012
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Konferenzbeitrag: Gene interaction profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed nerve allograft

Mathot, Femke / Rbia, Nadia / Van Wijnen, Andre / Bishop, Allen / Shin, Alexander

2020 , Seite(n) IFSSH19–748

Veranstaltung/Kongress	14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT); Berlin; ; International Federation of Societies for Hand Therapy; 2019
Schlagwörter	Medizin, Gesundheit ; Differentiated MSCs ; undifferentiated MSCs ; gene expression ; nerve regeneration ; stem cells ; nerve allografts
Erscheinungsdatum	2020-02-06
Verlag	German Medical Science GMS Publishing House; Düsseldorf
Dokumenttyp	Konferenzbeitrag
DOI	10.3205/19ifssh1391
Datenquelle	German Medical Science

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Konferenzbeitrag: The introduction of human Mesenchymal Stem Cells to clinically available nerve substitutes

Mathot, Femke / Rbia, Nadia / Bishop, Allen / Van Wijnen, Andre / Shin, Alexander

2020 , Seite(n) IFSSH19–737

Veranstaltung/Kongress	14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT); Berlin; ; International Federation of Societies for Hand Therapy; 2019
Schlagwörter	Medizin, Gesundheit ; Neuragen nerve guide ; avance nerve graft ; nerve reconstruction ; stem cells
Erscheinungsdatum	2020-02-06
Verlag	German Medical Science GMS Publishing House; Düsseldorf
Dokumenttyp	Konferenzbeitrag
DOI	10.3205/19ifssh1386
Datenquelle	German Medical Science

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