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Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy

Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i)...

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Autores principales: Marquardt, Laura M., Doulames, Vanessa M., Wang, Alice T., Dubbin, Karen, Suhar, Riley A., Kratochvil, Michael J., Medress, Zachary A., Plant, Giles W., Heilshorn, Sarah C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112763/
https://www.ncbi.nlm.nih.gov/pubmed/32270042
http://dx.doi.org/10.1126/sciadv.aaz1039
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author Marquardt, Laura M.
Doulames, Vanessa M.
Wang, Alice T.
Dubbin, Karen
Suhar, Riley A.
Kratochvil, Michael J.
Medress, Zachary A.
Plant, Giles W.
Heilshorn, Sarah C.
author_facet Marquardt, Laura M.
Doulames, Vanessa M.
Wang, Alice T.
Dubbin, Karen
Suhar, Riley A.
Kratochvil, Michael J.
Medress, Zachary A.
Plant, Giles W.
Heilshorn, Sarah C.
author_sort Marquardt, Laura M.
collection PubMed
description Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.
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spelling pubmed-71127632020-04-08 Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy Marquardt, Laura M. Doulames, Vanessa M. Wang, Alice T. Dubbin, Karen Suhar, Riley A. Kratochvil, Michael J. Medress, Zachary A. Plant, Giles W. Heilshorn, Sarah C. Sci Adv Research Articles Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies. American Association for the Advancement of Science 2020-04-01 /pmc/articles/PMC7112763/ /pubmed/32270042 http://dx.doi.org/10.1126/sciadv.aaz1039 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Marquardt, Laura M.
Doulames, Vanessa M.
Wang, Alice T.
Dubbin, Karen
Suhar, Riley A.
Kratochvil, Michael J.
Medress, Zachary A.
Plant, Giles W.
Heilshorn, Sarah C.
Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy
title Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy
title_full Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy
title_fullStr Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy
title_full_unstemmed Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy
title_short Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy
title_sort designer, injectable gels to prevent transplanted schwann cell loss during spinal cord injury therapy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112763/
https://www.ncbi.nlm.nih.gov/pubmed/32270042
http://dx.doi.org/10.1126/sciadv.aaz1039
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