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), 2024. Published by Science Publishing Group

Keywords

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

References

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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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