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Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion
Spinal fusion surgery is a surgical technique that connects one or more vertebrae at the same time to prevent movement between the vertebrae. Although synthetic bone substitutes or osteogenesis-inducing recombinant proteins were introduced to promote bone union, the rate of revision surgery is still...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585955/ https://www.ncbi.nlm.nih.gov/pubmed/36180050 http://dx.doi.org/10.1093/stcltm/szac052 |
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author | Cho, Sumin Choi, Hyemin Jeong, Hyundoo Kwon, Su Yeon Roh, Eun Ji Jeong, Kwang-Hun Baek, Inho Kim, Byoung Ju Lee, Soo-Hong Han, Inbo Cha, Jae Min |
author_facet | Cho, Sumin Choi, Hyemin Jeong, Hyundoo Kwon, Su Yeon Roh, Eun Ji Jeong, Kwang-Hun Baek, Inho Kim, Byoung Ju Lee, Soo-Hong Han, Inbo Cha, Jae Min |
author_sort | Cho, Sumin |
collection | PubMed |
description | Spinal fusion surgery is a surgical technique that connects one or more vertebrae at the same time to prevent movement between the vertebrae. Although synthetic bone substitutes or osteogenesis-inducing recombinant proteins were introduced to promote bone union, the rate of revision surgery is still high due to pseudarthrosis. To promote successful fusion after surgery, stem cells with or without biomaterials were introduced; however, conventional 2D-culture environments have resulted in a considerable loss of the innate therapeutic properties of stem cells. Therefore, we conducted a preclinical study applying 3D-spheroids of human bone marrow-dewrived mesenchymal stem cells (MSCs) to a mouse spinal fusion model. First, we built a large-scale manufacturing platform for MSC spheroids, which is applicable to good manufacturing practice (GMP). Comprehensive biomolecular examinations, which include liquid chromatography-mass spectrometry and bioinformatics could suggest a framework of quality control (QC) standards for the MSC spheroid product regarding the identity, purity, viability, and potency. In our animal study, the mass-produced and quality-controlled MSC spheroids, either undifferentiated or osteogenically differentiated were well-integrated into decorticated bone of the lumbar spine, and efficiently improved angiogenesis, bone regeneration, and mechanical stability with statistical significance compared to 2D-cultured MSCs. This study proposes a GMP-applicable bioprocessing platform and QC directions of MSC spheroids aiming for their clinical application in spinal fusion surgery as a new bone graft substitute. |
format | Online Article Text |
id | pubmed-9585955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-95859552022-10-24 Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion Cho, Sumin Choi, Hyemin Jeong, Hyundoo Kwon, Su Yeon Roh, Eun Ji Jeong, Kwang-Hun Baek, Inho Kim, Byoung Ju Lee, Soo-Hong Han, Inbo Cha, Jae Min Stem Cells Transl Med Tissue Engineering and Regenerative Medicine Spinal fusion surgery is a surgical technique that connects one or more vertebrae at the same time to prevent movement between the vertebrae. Although synthetic bone substitutes or osteogenesis-inducing recombinant proteins were introduced to promote bone union, the rate of revision surgery is still high due to pseudarthrosis. To promote successful fusion after surgery, stem cells with or without biomaterials were introduced; however, conventional 2D-culture environments have resulted in a considerable loss of the innate therapeutic properties of stem cells. Therefore, we conducted a preclinical study applying 3D-spheroids of human bone marrow-dewrived mesenchymal stem cells (MSCs) to a mouse spinal fusion model. First, we built a large-scale manufacturing platform for MSC spheroids, which is applicable to good manufacturing practice (GMP). Comprehensive biomolecular examinations, which include liquid chromatography-mass spectrometry and bioinformatics could suggest a framework of quality control (QC) standards for the MSC spheroid product regarding the identity, purity, viability, and potency. In our animal study, the mass-produced and quality-controlled MSC spheroids, either undifferentiated or osteogenically differentiated were well-integrated into decorticated bone of the lumbar spine, and efficiently improved angiogenesis, bone regeneration, and mechanical stability with statistical significance compared to 2D-cultured MSCs. This study proposes a GMP-applicable bioprocessing platform and QC directions of MSC spheroids aiming for their clinical application in spinal fusion surgery as a new bone graft substitute. Oxford University Press 2022-10-01 /pmc/articles/PMC9585955/ /pubmed/36180050 http://dx.doi.org/10.1093/stcltm/szac052 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | Tissue Engineering and Regenerative Medicine Cho, Sumin Choi, Hyemin Jeong, Hyundoo Kwon, Su Yeon Roh, Eun Ji Jeong, Kwang-Hun Baek, Inho Kim, Byoung Ju Lee, Soo-Hong Han, Inbo Cha, Jae Min Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion |
title | Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion |
title_full | Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion |
title_fullStr | Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion |
title_full_unstemmed | Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion |
title_short | Preclinical Study of Human Bone Marrow-Derived Mesenchymal Stem Cells Using a 3-Dimensional Manufacturing Setting for Enhancing Spinal Fusion |
title_sort | preclinical study of human bone marrow-derived mesenchymal stem cells using a 3-dimensional manufacturing setting for enhancing spinal fusion |
topic | Tissue Engineering and Regenerative Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585955/ https://www.ncbi.nlm.nih.gov/pubmed/36180050 http://dx.doi.org/10.1093/stcltm/szac052 |
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