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Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells
INTRODUCTION: Mesenchymal stromal cells (MSCs) have opened a new window to treat inflammatory and non-inflammatory diseases. Nonetheless, their clinical applications require rigorous control and monitoring procedures to ensure full compliance with the principles of good manufacturing practice (GMP)....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137136/ https://www.ncbi.nlm.nih.gov/pubmed/35619148 http://dx.doi.org/10.1186/s13287-022-02899-9 |
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author | Tayebi, Behnoosh Babaahmadi, Mahnaz Pakzad, Mohammad Hajinasrollah, Mostafa Mostafaei, Farhad Jahangiri, Shahrbanoo Kamali, Amir Baharvand, Hossein Baghaban Eslaminejad, Mohamadreza Hassani, Seyedeh-Nafiseh Hajizadeh-Saffar, Ensiyeh |
author_facet | Tayebi, Behnoosh Babaahmadi, Mahnaz Pakzad, Mohammad Hajinasrollah, Mostafa Mostafaei, Farhad Jahangiri, Shahrbanoo Kamali, Amir Baharvand, Hossein Baghaban Eslaminejad, Mohamadreza Hassani, Seyedeh-Nafiseh Hajizadeh-Saffar, Ensiyeh |
author_sort | Tayebi, Behnoosh |
collection | PubMed |
description | INTRODUCTION: Mesenchymal stromal cells (MSCs) have opened a new window to treat inflammatory and non-inflammatory diseases. Nonetheless, their clinical applications require rigorous control and monitoring procedures to ensure full compliance with the principles of good manufacturing practice (GMP). Various evaluations should be passed in conjunction with the development of these newly emerging therapeutic products from bench-to-bedside. These evaluations include in vitro characterization, preclinical studies, and clinical trials to ensure product safety and efficacy. Therefore, a robust and well-designed preclinical study is critical to confirm product safety. This study aims to determine the probable toxicity effects of local and systemic injections of cryopreserved human bone marrow-derived clonal MSCs (BM-cMSCs) during subacute and subchronic periods of time. METHODS: BM-cMSCs were characterized according to the International Society for Cell and Gene Therapy (ISCT) criteria for MSCs. Both safety and toxicity of the BM-cMSCs population produced under GMP-compatible conditions were assessed in both sexes of Sprague Dawley (SD) rats via systemic intravenous (IV) administration and local injection in intervertebral disc (IVD). Behavioral changes, clinical signs of toxicity, and changes in body weight, water and food consumption were the important variables for product toxicity testing over 14 consecutive days during the subacute period and 90 consecutive days during the subchronic period. At the end of the assessment periods, the rats were killed for histopathology analysis of the target tissues. The BM-cMSCs potential for tumorigenicity was checked in nude mice. RESULTS: Single IV and IVD injections of BM-cMSCs did not cause significant signs of clinical toxicity, or changes in laboratory and histopathology data during the subacute (14 day) and subchronic (90 day) periods. Ex vivo-expanded and cryopreserved BM-cMSCs did not induce tumor formation in nude mice. CONCLUSION: The results suggest that local and systemic administrations of xenogeneic BM-cMSCs in both sexes of SD rats do not cause toxicity during the subacute and subchronic periods of time. Also, BM-cMSCs were non-tumorigenic in nude mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02899-9. |
format | Online Article Text |
id | pubmed-9137136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91371362022-05-28 Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells Tayebi, Behnoosh Babaahmadi, Mahnaz Pakzad, Mohammad Hajinasrollah, Mostafa Mostafaei, Farhad Jahangiri, Shahrbanoo Kamali, Amir Baharvand, Hossein Baghaban Eslaminejad, Mohamadreza Hassani, Seyedeh-Nafiseh Hajizadeh-Saffar, Ensiyeh Stem Cell Res Ther Research INTRODUCTION: Mesenchymal stromal cells (MSCs) have opened a new window to treat inflammatory and non-inflammatory diseases. Nonetheless, their clinical applications require rigorous control and monitoring procedures to ensure full compliance with the principles of good manufacturing practice (GMP). Various evaluations should be passed in conjunction with the development of these newly emerging therapeutic products from bench-to-bedside. These evaluations include in vitro characterization, preclinical studies, and clinical trials to ensure product safety and efficacy. Therefore, a robust and well-designed preclinical study is critical to confirm product safety. This study aims to determine the probable toxicity effects of local and systemic injections of cryopreserved human bone marrow-derived clonal MSCs (BM-cMSCs) during subacute and subchronic periods of time. METHODS: BM-cMSCs were characterized according to the International Society for Cell and Gene Therapy (ISCT) criteria for MSCs. Both safety and toxicity of the BM-cMSCs population produced under GMP-compatible conditions were assessed in both sexes of Sprague Dawley (SD) rats via systemic intravenous (IV) administration and local injection in intervertebral disc (IVD). Behavioral changes, clinical signs of toxicity, and changes in body weight, water and food consumption were the important variables for product toxicity testing over 14 consecutive days during the subacute period and 90 consecutive days during the subchronic period. At the end of the assessment periods, the rats were killed for histopathology analysis of the target tissues. The BM-cMSCs potential for tumorigenicity was checked in nude mice. RESULTS: Single IV and IVD injections of BM-cMSCs did not cause significant signs of clinical toxicity, or changes in laboratory and histopathology data during the subacute (14 day) and subchronic (90 day) periods. Ex vivo-expanded and cryopreserved BM-cMSCs did not induce tumor formation in nude mice. CONCLUSION: The results suggest that local and systemic administrations of xenogeneic BM-cMSCs in both sexes of SD rats do not cause toxicity during the subacute and subchronic periods of time. Also, BM-cMSCs were non-tumorigenic in nude mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-02899-9. BioMed Central 2022-05-26 /pmc/articles/PMC9137136/ /pubmed/35619148 http://dx.doi.org/10.1186/s13287-022-02899-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Tayebi, Behnoosh Babaahmadi, Mahnaz Pakzad, Mohammad Hajinasrollah, Mostafa Mostafaei, Farhad Jahangiri, Shahrbanoo Kamali, Amir Baharvand, Hossein Baghaban Eslaminejad, Mohamadreza Hassani, Seyedeh-Nafiseh Hajizadeh-Saffar, Ensiyeh Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells |
title | Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells |
title_full | Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells |
title_fullStr | Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells |
title_full_unstemmed | Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells |
title_short | Standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells |
title_sort | standard toxicity study of clinical-grade allogeneic human bone marrow-derived clonal mesenchymal stromal cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137136/ https://www.ncbi.nlm.nih.gov/pubmed/35619148 http://dx.doi.org/10.1186/s13287-022-02899-9 |
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