Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter

Katarzyna Kozłowska; Klaudia Różczka; Marcin Michał Strojny; Sonia Brodowska; Amber Lopez; Maria Siemionow

doi:doi:10.11648/j.js.20221006.11

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Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter

Katarzyna Kozłowska, Klaudia Różczka, Marcin Michał Strojny, Sonia Brodowska, Amber Lopez, Maria Siemionow

Published in Journal of Surgery (Volume 10, Issue 6)

Received: 12 September 2022 Accepted: 15 November 2022 Published: 29 November 2022

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Abstract

Different therapies have been reported to support nerve gap regeneration following traumatic nerve injuries. Clinically, lack of the donor nerve or nerve conduit match is challenging and may have a negative impact on nerve regeneration and functional outcomes. This study introduces an innovative approach for management of nerve gaps in the cases of nerve conduit mismatch by applying the unmatched human epineural conduit (hEC) of large diameter supported with human mesenchymal stem cells (hMSC). Following resection of 20mm of a sciatic nerve in the athymic nude rat model (Crl: NIH-Foxn1rnu): 24 animals were assessed in four experimental groups of n=6 rats each: Group 1- no repair control, Group 2- nerve autograft repair, Group 3- hEC filled with 1mL of saline, Group 4- hEC filled with 3 × 10⁶of hMSC. We performed functional tests of: toe-spread and pinprick, Gastrocnemius Muscle Index (GMI) and muscle fiber area ratio, immunofluorescence staining for vWF, VEGF, S-100, GFAP, Laminin B, NGF for assessment of nerve regeneration, assessment of human origin of the MSC by HLA-1, HLA-DR and human MSC labeling with PKH26 dye, and Toluidine blue staining of nerve cross sections for histomorphometric analysis of the myelin thickness, axonal density, fiber diameter, and percentage of the myelinated nerve fibers. The hEC supported with human MSC group was second to regain best recovery, following the autograft group, regarding functional assessments of toe-spread and pinprick (p = 0.0032 and p = 0.0079 respectively). Gastrocnemius Muscle Index analysis revealed comparable results between the autograft and hEC supported with hMSC and significantly better results when compared with no gap repair (p < 0.0001 and p = 0.0092 respectively). Significantly increased number of myelinated fibers was observed in the large diameter hEC enhanced with hMSC when compared with the control group of large diameters hEC filled with saline. The myelin sheath thickness, fiber diameters, axonal density and percentage of myelinated fibers analysis results were comparable between the large diameter hEC enhanced with hMSC and the control group of large diameters hEC filled with saline. We confirmed the supportive role of hMSC in the improvement of nerve regeneration after nerve gap repair with hEC of large-unmatched diameter. At 12-weeks we demonstrated comparable functional recovery, histomorphometric parameters and growth factors expression between the autograft repair and the hEC enhanced with hMSC, whereas significantly worse recovery was noted in the control group of hEC filled with saline, further confirming regenerative potential of MSC.

Published in	Journal of Surgery (Volume 10, Issue 6)
DOI	10.11648/j.js.20221006.11
Page(s)	193-205
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Human Epineural Conduit, Conduit Diameter Mismatch, Mesenchymal Stem Cells, Peripheral Nerve Regeneration

References

[1]	Yi S, Zhang Y, Gu X, Huang L, Zhang K, Qian T, et al. Application of stem cells in peripheral nerve regeneration. Burn Trauma. 2020; 8.
[2]	Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biomaterials approach to peripheral nerve regeneration: Bridging the peripheral nerve gap and enhancing functional recovery. J R Soc Interface. 2012; 9 (67): 202–21.
[3]	Sarker M, Naghieh S, McInnes AD, Schreyer DJ, Chen X. Strategic Design and Fabrication of Nerve Guidance Conduits for Peripheral Nerve Regeneration. Biotechnol J. 2018; 1 (7): 1–16.
[4]	Zhao X, Fan C, Wang J, Xiong H, Zhu T, Liu Y, et al. Bioinspired multichannel nerve guidance conduit based on shape memory nanofibers for potential application in peripheral nerve repair. ACS Nano. 2020; 14 (10): 12579–95.
[5]	Houshyar S, Bhattacharyya A, Shanks R. Peripheral Nerve Conduit: Materials and Structures. ACS Chem Neurosci. 2019; 10 (8): 3349–65.
[6]	Sarker MD, Naghieh S, McInnes AD, Schreyer DJ, Chen X. Regeneration of peripheral nerves by nerve guidance conduits: Influence of design, biopolymers, cells, growth factors, and physical stimuli. Prog Neurobiol [Internet]. 2018; 171 (July): 125–50. Available from: https://doi.org/10.1016/j.pneurobio.2018.07.002
[7]	Kerns JM, Walter JS, Patetta MJ, Sood A, Hussain AK, Chung JJ, et al. Histological Assessment of Wallerian Degeneration of the Rat Tibial Nerve following Crush and Transection Injuries. J Reconstr Microsurg. 2021; 37 (5): 391–404.
[8]	Gordon T. Peripheral nerve regeneration and muscle reinnervation. Int J Mol Sci. 2020; 21 (22): 1–24.
[9]	Gordon T. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans. Neurotherapeutics. 2016; 13 (2): 295–310.
[10]	Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review. Neurosurg Focus. 2004; 16 (5): 1–7.
[11]	Vijayavenkataraman S. Nerve guide conduits for peripheral nerve injury repair: A review on design, materials and fabrication methods. Acta Biomater [Internet]. 2020; 106: 54–69. Available from: https://doi.org/10.1016/j.actbio.2020.02.003
[12]	Ray WZ, Mackinnon SE. Management of nerve gaps: Autografts, allografts, nerve transfers, and end-to-side neurorrhaphy. Exp Neurol [Internet]. 2010; 223 (1): 77–85. Available from: http://dx.doi.org/10.1016/j.expneurol.2009.03.031
[13]	Siemionow M, Uygur S, Ozturk C, Siemionow K. Techniques, and materials for enhancement of peripheral nerve regeneration: A literature review. Microsurgery. 2013; 33 (4): 318–28.
[14]	Tamaki T. Bridging long gap peripheral nerve injury using skeletal muscle-derived multipotent stem cells. Neural Regen Res. 2014; 9 (14): 1333–6.
[15]	Meek MF, Coert JH. Clinical use of nerve conduits in peripheral-nerve repair: Review of the literature. J Reconstr Microsurg. 2002; 18 (2): 97–109.
[16]	Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol. 2006; 198 (1): 54–64.
[17]	Wakao S, Matsuse D, Dezawa M. Mesenchymal stem cells as a source of schwann cells: Their anticipated use in peripheral nerve regeneration. Cells Tissues Organs. 2014; 200 (1): 31–41.
[18]	Chen Q, Long Y, Yuan X, Zou LL, Sun J, Chen S, et al. Protective effects of bone marrow stromal cell transplantation in injured rodent brain: Synthesis of neurotrophic factors. J Neurosci Res. 2005; 80 (5): 611–9.
[19]	Kan I, Barhum Y, Melamed E, Offen D. Mesenchymal Stem Cells Stimulate Endogenous Neurogenesis in the Subventricular Zone of Adult Mice. Stem Cell Rev Reports. 2011; 7 (2): 404–12.
[20]	Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, et al. Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol - Hear Circ Physiol. 2004; 287 (656-6): 5–7.
[21]	Tang YL, Zhao Q, Zhang YC, Cheng L, Liu M, Shi J, et al. Autologous mesenchymal stem cell transplantation induces VEGF and neovascularization in ischemic myocardium. Regul Pept. 2004; 117 (1): 3–10.
[22]	Lukaszuk M, Kwiecien G, Madajka M, Uygur S, Drews M, Siemionow M. Repair of the peripheral nerve gap with epineural sheath conduit to prevent muscle denervation atrophy in the diabetic rat model. Pol Prz Chir Polish J Surg. 2013; 85 (7): 387–94.
[23]	Siemionow M, Uygur S, Madajka M. Application of Epineural Sheath as a Novel Approach for Fat Volume Maintenance. Ann Plast Surg. 2017; 79 (6): 606–12.
[24]	Siemionow M, Cwykiel J, Uygur S, Kwiecien G, Oztürk C, Szopinski J, et al. Application of epineural sheath conduit for restoration of 6-cm long nerve defects in a sheep median nerve model. Microsurgery. 2019; 39 (4): 332–9.
[25]	Klimczak A, Siemionow M, Futoma K, Jundzill A, Patrzalek D. Assessment of immunologic, proangiogenic and neurogenic properties of human peripheral nerve epineurium for potential clinical application. Histol Histopathol. 2017; 32 (11): 1197–205.
[26]	Siemionow M, Strojny MM, Kozlowska K, Brodowska S, Grau-Kazmierczak W, Cwykd with Human Mesenchymal Stem Cells as a Novel Therapyiel J. Application of Human Epineural Conduit Supporte for Enhancement of Nerve Gap Regeneration. Stem Cell Rev Reports [Internet]. 2022; 18 (2): 642–59. Available from: https://doi.org/10.1007/s12015-021-10301-z
[27]	Thibodeau A, Galbraith T, Fauvel CM, Khuong HT, Berthod F. Repair of peripheral nerve injuries using a prevascularized cell-based tissue-engineered nerve conduit. Biomaterials. 2022; 280 (July 2021).
[28]	Nijhuis THJ, Bodar CWJ, Van Neck JW, Walbeehm ET, Siemionow M, Madajka M, et al. Natural conduits for bridging a 15-mm nerve defect: Comparison of the vein supported by muscle and bone marrow stromal cells with a nerve autograft. J Plast Reconstr Aesthetic Surg [Internet]. 2013; 66 (2): 251–9. Available from: http://dx.doi.org/10.1016/j.bjps.2012.09.011
[29]	Meek MF, Coert JH. US Food and Drug Administration /Conformit Europe- approved absorbable nerve conduits for clinical repair of peripheral and cranial nerves. Ann Plast Surg. 2008; 60 (4): 466–72.
[30]	Su H, Xu F, Sun H, Fu X, Zhao Y. Preparation and Evaluation of BDNF Composite Conduits for Regeneration of Sciatic Nerve Defect in Rats. J Pharm Sci [Internet]. 2020; 109 (7): 2189–95. Available from: https://doi.org/10.1016/j.xphs.2020.03.027
[31]	Huang YC, Huang YY. Biomaterials and strategies for nerve regeneration. Artif Organs. 2006; 30 (7): 514–22.
[32]	Grinsell D, Keating CP. Peripheral Nerve Reconstruction after Injury: A Review of Clinical and Experimental Therapies. Biomed Res Int. 2014; 2014.
[33]	Chiu DTW, Strauch B. A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. Vol. 86, Plastic and Reconstructive Surgery. 1990. p. 928–34.
[34]	Sehrbundt Viale E, Brambilla M, Martelli A, Pau A VG. Muscle basal lamina as a grafting material for elongation of axons from rat brain. Acta Neurochir. 1991; 109 (3-4): 1.
[35]	Suhar RA, States U, Marquardt LM, States U, Buabbas H. Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits. 2021; 7 (9): 4209–20.
[36]	Yang Y, Yuan X, Ding F, Yao D, Gu Y, Liu J, et al. Repair of Rat Sciatic Nerve Gap by a Silk Fibroin-Based Scaffold Added with Bone Marrow Mesenchymal Stem Cells. Tissue Eng - Part A. 2011; 17 (17–18): 2231–44.
[37]	Giusti G, Shin RH, Lee JY, Mattar TG, Bishop AT SA. The influence of nerve conduits diameter in motor nerve recovery after segmental nerve repair. Microsurgery. 2014; 34 (8): 646–52.
[38]	Abbas OL, Ozatik O, Gonen ZB, Koçman AE, Dag I, Ozatik FY, et al. Bone Marrow Mesenchymal Stem Cell Transplantation Enhances Nerve Regeneration in a Rat Model of Hindlimb Replantation. Plast Reconstr Surg. 2019; 143 (4): 758e-768e.
[39]	Yousefi F, Lavi Arab F, Nikkhah K, Amiri H, Mahmoudi M. Novel approaches using mesenchymal stem cells for curing peripheral nerve injuries. Life Sci. 2019; 221 (February): 99–108.
[40]	Cui Y, Yao Y, Zhao Y, Xiao Z, Cao Z, Han S, et al. Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs. J Tissue Eng Regen Med. 2018; 12 (5): 1285–96.

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Katarzyna Kozłowska, Klaudia Różczka, Marcin Michał Strojny, Sonia Brodowska, Amber Lopez, et al. (2022). Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter. Journal of Surgery, 10(6), 193-205. https://doi.org/10.11648/j.js.20221006.11

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ACS Style

Katarzyna Kozłowska; Klaudia Różczka; Marcin Michał Strojny; Sonia Brodowska; Amber Lopez, et al. Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter. J. Surg. 2022, 10(6), 193-205. doi: 10.11648/j.js.20221006.11

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AMA Style

Katarzyna Kozłowska, Klaudia Różczka, Marcin Michał Strojny, Sonia Brodowska, Amber Lopez, et al. Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter. J Surg. 2022;10(6):193-205. doi: 10.11648/j.js.20221006.11

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@article{10.11648/j.js.20221006.11,
  author = {Katarzyna Kozłowska and Klaudia Różczka and Marcin Michał Strojny and Sonia Brodowska and Amber Lopez and Maria Siemionow},
  title = {Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter},
  journal = {Journal of Surgery},
  volume = {10},
  number = {6},
  pages = {193-205},
  doi = {10.11648/j.js.20221006.11},
  url = {https://doi.org/10.11648/j.js.20221006.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.js.20221006.11},
  abstract = {Different therapies have been reported to support nerve gap regeneration following traumatic nerve injuries. Clinically, lack of the donor nerve or nerve conduit match is challenging and may have a negative impact on nerve regeneration and functional outcomes. This study introduces an innovative approach for management of nerve gaps in the cases of nerve conduit mismatch by applying the unmatched human epineural conduit (hEC) of large diameter supported with human mesenchymal stem cells (hMSC). Following resection of 20mm of a sciatic nerve in the athymic nude rat model (Crl: NIH-Foxn1rnu): 24 animals were assessed in four experimental groups of n=6 rats each: Group 1- no repair control, Group 2- nerve autograft repair, Group 3- hEC filled with 1mL of saline, Group 4- hEC filled with 3 × 106 of hMSC. We performed functional tests of: toe-spread and pinprick, Gastrocnemius Muscle Index (GMI) and muscle fiber area ratio, immunofluorescence staining for vWF, VEGF, S-100, GFAP, Laminin B, NGF for assessment of nerve regeneration, assessment of human origin of the MSC by HLA-1, HLA-DR and human MSC labeling with PKH26 dye, and Toluidine blue staining of nerve cross sections for histomorphometric analysis of the myelin thickness, axonal density, fiber diameter, and percentage of the myelinated nerve fibers. The hEC supported with human MSC group was second to regain best recovery, following the autograft group, regarding functional assessments of toe-spread and pinprick (p = 0.0032 and p = 0.0079 respectively). Gastrocnemius Muscle Index analysis revealed comparable results between the autograft and hEC supported with hMSC and significantly better results when compared with no gap repair (p < 0.0001 and p = 0.0092 respectively). Significantly increased number of myelinated fibers was observed in the large diameter hEC enhanced with hMSC when compared with the control group of large diameters hEC filled with saline. The myelin sheath thickness, fiber diameters, axonal density and percentage of myelinated fibers analysis results were comparable between the large diameter hEC enhanced with hMSC and the control group of large diameters hEC filled with saline. We confirmed the supportive role of hMSC in the improvement of nerve regeneration after nerve gap repair with hEC of large-unmatched diameter. At 12-weeks we demonstrated comparable functional recovery, histomorphometric parameters and growth factors expression between the autograft repair and the hEC enhanced with hMSC, whereas significantly worse recovery was noted in the control group of hEC filled with saline, further confirming regenerative potential of MSC.},
 year = {2022}
}

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TY  - JOUR
T1  - Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter
AU  - Katarzyna Kozłowska
AU  - Klaudia Różczka
AU  - Marcin Michał Strojny
AU  - Sonia Brodowska
AU  - Amber Lopez
AU  - Maria Siemionow
Y1  - 2022/11/29
PY  - 2022
N1  - https://doi.org/10.11648/j.js.20221006.11
DO  - 10.11648/j.js.20221006.11
T2  - Journal of Surgery
JF  - Journal of Surgery
JO  - Journal of Surgery
SP  - 193
EP  - 205
PB  - Science Publishing Group
SN  - 2330-0930
UR  - https://doi.org/10.11648/j.js.20221006.11
AB  - Different therapies have been reported to support nerve gap regeneration following traumatic nerve injuries. Clinically, lack of the donor nerve or nerve conduit match is challenging and may have a negative impact on nerve regeneration and functional outcomes. This study introduces an innovative approach for management of nerve gaps in the cases of nerve conduit mismatch by applying the unmatched human epineural conduit (hEC) of large diameter supported with human mesenchymal stem cells (hMSC). Following resection of 20mm of a sciatic nerve in the athymic nude rat model (Crl: NIH-Foxn1rnu): 24 animals were assessed in four experimental groups of n=6 rats each: Group 1- no repair control, Group 2- nerve autograft repair, Group 3- hEC filled with 1mL of saline, Group 4- hEC filled with 3 × 106 of hMSC. We performed functional tests of: toe-spread and pinprick, Gastrocnemius Muscle Index (GMI) and muscle fiber area ratio, immunofluorescence staining for vWF, VEGF, S-100, GFAP, Laminin B, NGF for assessment of nerve regeneration, assessment of human origin of the MSC by HLA-1, HLA-DR and human MSC labeling with PKH26 dye, and Toluidine blue staining of nerve cross sections for histomorphometric analysis of the myelin thickness, axonal density, fiber diameter, and percentage of the myelinated nerve fibers. The hEC supported with human MSC group was second to regain best recovery, following the autograft group, regarding functional assessments of toe-spread and pinprick (p = 0.0032 and p = 0.0079 respectively). Gastrocnemius Muscle Index analysis revealed comparable results between the autograft and hEC supported with hMSC and significantly better results when compared with no gap repair (p < 0.0001 and p = 0.0092 respectively). Significantly increased number of myelinated fibers was observed in the large diameter hEC enhanced with hMSC when compared with the control group of large diameters hEC filled with saline. The myelin sheath thickness, fiber diameters, axonal density and percentage of myelinated fibers analysis results were comparable between the large diameter hEC enhanced with hMSC and the control group of large diameters hEC filled with saline. We confirmed the supportive role of hMSC in the improvement of nerve regeneration after nerve gap repair with hEC of large-unmatched diameter. At 12-weeks we demonstrated comparable functional recovery, histomorphometric parameters and growth factors expression between the autograft repair and the hEC enhanced with hMSC, whereas significantly worse recovery was noted in the control group of hEC filled with saline, further confirming regenerative potential of MSC.
VL  - 10
IS  - 6
ER  -

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Author Information

Katarzyna Kozłowska
Klaudia Różczka
Marcin Michał Strojny
Sonia Brodowska

Department of Orthopaedics, University of Illinois at Chicago, Chicago, USA
Amber Lopez

Department of Orthopaedics, University of Illinois at Chicago, Chicago, USA
Maria Siemionow

Department of Orthopaedics, University of Illinois at Chicago, Chicago, USA

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APA Style

Katarzyna Kozłowska, Klaudia Różczka, Marcin Michał Strojny, Sonia Brodowska, Amber Lopez, et al. (2022). Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter. Journal of Surgery, 10(6), 193-205. https://doi.org/10.11648/j.js.20221006.11

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ACS Style

Katarzyna Kozłowska; Klaudia Różczka; Marcin Michał Strojny; Sonia Brodowska; Amber Lopez, et al. Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter. J. Surg. 2022, 10(6), 193-205. doi: 10.11648/j.js.20221006.11

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AMA Style

Katarzyna Kozłowska, Klaudia Różczka, Marcin Michał Strojny, Sonia Brodowska, Amber Lopez, et al. Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter. J Surg. 2022;10(6):193-205. doi: 10.11648/j.js.20221006.11

Copy | Download

@article{10.11648/j.js.20221006.11,
  author = {Katarzyna Kozłowska and Klaudia Różczka and Marcin Michał Strojny and Sonia Brodowska and Amber Lopez and Maria Siemionow},
  title = {Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter},
  journal = {Journal of Surgery},
  volume = {10},
  number = {6},
  pages = {193-205},
  doi = {10.11648/j.js.20221006.11},
  url = {https://doi.org/10.11648/j.js.20221006.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.js.20221006.11},
  abstract = {Different therapies have been reported to support nerve gap regeneration following traumatic nerve injuries. Clinically, lack of the donor nerve or nerve conduit match is challenging and may have a negative impact on nerve regeneration and functional outcomes. This study introduces an innovative approach for management of nerve gaps in the cases of nerve conduit mismatch by applying the unmatched human epineural conduit (hEC) of large diameter supported with human mesenchymal stem cells (hMSC). Following resection of 20mm of a sciatic nerve in the athymic nude rat model (Crl: NIH-Foxn1rnu): 24 animals were assessed in four experimental groups of n=6 rats each: Group 1- no repair control, Group 2- nerve autograft repair, Group 3- hEC filled with 1mL of saline, Group 4- hEC filled with 3 × 106 of hMSC. We performed functional tests of: toe-spread and pinprick, Gastrocnemius Muscle Index (GMI) and muscle fiber area ratio, immunofluorescence staining for vWF, VEGF, S-100, GFAP, Laminin B, NGF for assessment of nerve regeneration, assessment of human origin of the MSC by HLA-1, HLA-DR and human MSC labeling with PKH26 dye, and Toluidine blue staining of nerve cross sections for histomorphometric analysis of the myelin thickness, axonal density, fiber diameter, and percentage of the myelinated nerve fibers. The hEC supported with human MSC group was second to regain best recovery, following the autograft group, regarding functional assessments of toe-spread and pinprick (p = 0.0032 and p = 0.0079 respectively). Gastrocnemius Muscle Index analysis revealed comparable results between the autograft and hEC supported with hMSC and significantly better results when compared with no gap repair (p < 0.0001 and p = 0.0092 respectively). Significantly increased number of myelinated fibers was observed in the large diameter hEC enhanced with hMSC when compared with the control group of large diameters hEC filled with saline. The myelin sheath thickness, fiber diameters, axonal density and percentage of myelinated fibers analysis results were comparable between the large diameter hEC enhanced with hMSC and the control group of large diameters hEC filled with saline. We confirmed the supportive role of hMSC in the improvement of nerve regeneration after nerve gap repair with hEC of large-unmatched diameter. At 12-weeks we demonstrated comparable functional recovery, histomorphometric parameters and growth factors expression between the autograft repair and the hEC enhanced with hMSC, whereas significantly worse recovery was noted in the control group of hEC filled with saline, further confirming regenerative potential of MSC.},
 year = {2022}
}

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TY  - JOUR
T1  - Human Mesenchymal Stem Cells Enhance Nerve Regeneration in Nerve Gap Repair with Human Epineural Conduit of a Large - Unmatched Diameter
AU  - Katarzyna Kozłowska
AU  - Klaudia Różczka
AU  - Marcin Michał Strojny
AU  - Sonia Brodowska
AU  - Amber Lopez
AU  - Maria Siemionow
Y1  - 2022/11/29
PY  - 2022
N1  - https://doi.org/10.11648/j.js.20221006.11
DO  - 10.11648/j.js.20221006.11
T2  - Journal of Surgery
JF  - Journal of Surgery
JO  - Journal of Surgery
SP  - 193
EP  - 205
PB  - Science Publishing Group
SN  - 2330-0930
UR  - https://doi.org/10.11648/j.js.20221006.11
AB  - Different therapies have been reported to support nerve gap regeneration following traumatic nerve injuries. Clinically, lack of the donor nerve or nerve conduit match is challenging and may have a negative impact on nerve regeneration and functional outcomes. This study introduces an innovative approach for management of nerve gaps in the cases of nerve conduit mismatch by applying the unmatched human epineural conduit (hEC) of large diameter supported with human mesenchymal stem cells (hMSC). Following resection of 20mm of a sciatic nerve in the athymic nude rat model (Crl: NIH-Foxn1rnu): 24 animals were assessed in four experimental groups of n=6 rats each: Group 1- no repair control, Group 2- nerve autograft repair, Group 3- hEC filled with 1mL of saline, Group 4- hEC filled with 3 × 106 of hMSC. We performed functional tests of: toe-spread and pinprick, Gastrocnemius Muscle Index (GMI) and muscle fiber area ratio, immunofluorescence staining for vWF, VEGF, S-100, GFAP, Laminin B, NGF for assessment of nerve regeneration, assessment of human origin of the MSC by HLA-1, HLA-DR and human MSC labeling with PKH26 dye, and Toluidine blue staining of nerve cross sections for histomorphometric analysis of the myelin thickness, axonal density, fiber diameter, and percentage of the myelinated nerve fibers. The hEC supported with human MSC group was second to regain best recovery, following the autograft group, regarding functional assessments of toe-spread and pinprick (p = 0.0032 and p = 0.0079 respectively). Gastrocnemius Muscle Index analysis revealed comparable results between the autograft and hEC supported with hMSC and significantly better results when compared with no gap repair (p < 0.0001 and p = 0.0092 respectively). Significantly increased number of myelinated fibers was observed in the large diameter hEC enhanced with hMSC when compared with the control group of large diameters hEC filled with saline. The myelin sheath thickness, fiber diameters, axonal density and percentage of myelinated fibers analysis results were comparable between the large diameter hEC enhanced with hMSC and the control group of large diameters hEC filled with saline. We confirmed the supportive role of hMSC in the improvement of nerve regeneration after nerve gap repair with hEC of large-unmatched diameter. At 12-weeks we demonstrated comparable functional recovery, histomorphometric parameters and growth factors expression between the autograft repair and the hEC enhanced with hMSC, whereas significantly worse recovery was noted in the control group of hEC filled with saline, further confirming regenerative potential of MSC.
VL  - 10
IS  - 6
ER  -

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