A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease

Cellular replacement therapy using mesenchymal stem cells (MSCs) and/or the delivery of growth factors are at the forefront of minimally invasive biological treatment options for Degenerative Disc Disease (DDD). In this study, we compared the therapeutic potential of a novel drug candidate, NTG-101...

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Autores principales: Matta, Ajay, Karim, Muhammad Zia, Gerami, Hoda, Benigno, Bettina, Erwin, W. Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292352/
https://www.ncbi.nlm.nih.gov/pubmed/34285277
http://dx.doi.org/10.1038/s41598-021-94173-w
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author Matta, Ajay
Karim, Muhammad Zia
Gerami, Hoda
Benigno, Bettina
Erwin, W. Mark
author_facet Matta, Ajay
Karim, Muhammad Zia
Gerami, Hoda
Benigno, Bettina
Erwin, W. Mark
author_sort Matta, Ajay
collection PubMed
description Cellular replacement therapy using mesenchymal stem cells (MSCs) and/or the delivery of growth factors are at the forefront of minimally invasive biological treatment options for Degenerative Disc Disease (DDD). In this study, we compared the therapeutic potential of a novel drug candidate, NTG-101 to MSCs, including rat cartilage derived stem cells (rCDSCs), bone marrow stem cells (rBMSCs) and human Umbilical Cord Derived Mesenchymal Stem Cells (hUCMSCs) for the treatment of DDD. We induced DDD using a validated image-guided needle puncture injury in rat-tail IVDs. Ten weeks post-injury, animals were randomized and injected with MSCs, NTG-101 or vehicle. At the end of the study, histological analysis of the IVD-Nucleus Pulposus (NPs) injected with NTG-101 or rCDSCs showed a healthy or mild degenerative phenotype in comparison to vehicle controls. Immunohistochemical analysis revealed strong expression of aggrecan, collagen 2, brachyury and Oct4 in IVD-NPs injected with NTG-101. Our results also demonstrated suppression of inflammation induced p38 and NFκB resulting in inhibition of catabolic genes, but activation of Smad-2/3, Erk-1/2 and Akt-dependent signaling inducing anabolic genes in IVD-NP on treatment with NTG-101. In conclusion, a single injection of NTG-101 into the degenerative disc demonstrated superior benefits compared to stem cell transplantation.
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spelling pubmed-82923522021-07-22 A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease Matta, Ajay Karim, Muhammad Zia Gerami, Hoda Benigno, Bettina Erwin, W. Mark Sci Rep Article Cellular replacement therapy using mesenchymal stem cells (MSCs) and/or the delivery of growth factors are at the forefront of minimally invasive biological treatment options for Degenerative Disc Disease (DDD). In this study, we compared the therapeutic potential of a novel drug candidate, NTG-101 to MSCs, including rat cartilage derived stem cells (rCDSCs), bone marrow stem cells (rBMSCs) and human Umbilical Cord Derived Mesenchymal Stem Cells (hUCMSCs) for the treatment of DDD. We induced DDD using a validated image-guided needle puncture injury in rat-tail IVDs. Ten weeks post-injury, animals were randomized and injected with MSCs, NTG-101 or vehicle. At the end of the study, histological analysis of the IVD-Nucleus Pulposus (NPs) injected with NTG-101 or rCDSCs showed a healthy or mild degenerative phenotype in comparison to vehicle controls. Immunohistochemical analysis revealed strong expression of aggrecan, collagen 2, brachyury and Oct4 in IVD-NPs injected with NTG-101. Our results also demonstrated suppression of inflammation induced p38 and NFκB resulting in inhibition of catabolic genes, but activation of Smad-2/3, Erk-1/2 and Akt-dependent signaling inducing anabolic genes in IVD-NP on treatment with NTG-101. In conclusion, a single injection of NTG-101 into the degenerative disc demonstrated superior benefits compared to stem cell transplantation. Nature Publishing Group UK 2021-07-20 /pmc/articles/PMC8292352/ /pubmed/34285277 http://dx.doi.org/10.1038/s41598-021-94173-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Matta, Ajay
Karim, Muhammad Zia
Gerami, Hoda
Benigno, Bettina
Erwin, W. Mark
A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease
title A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease
title_full A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease
title_fullStr A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease
title_full_unstemmed A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease
title_short A comparative study of mesenchymal stem cell transplantation and NTG-101 molecular therapy to treat degenerative disc disease
title_sort comparative study of mesenchymal stem cell transplantation and ntg-101 molecular therapy to treat degenerative disc disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292352/
https://www.ncbi.nlm.nih.gov/pubmed/34285277
http://dx.doi.org/10.1038/s41598-021-94173-w
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