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Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)

Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as...

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Autores principales: Bonfield, Tracey L., Sutton, Morgan T., Fletcher, David R., Reese-Koc, Jane, Roesch, Erica A., Lazarus, Hillard M., Chmiel, James F., Caplan, Arnold I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960767/
https://www.ncbi.nlm.nih.gov/pubmed/37259368
http://dx.doi.org/10.3390/ph16020220
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author Bonfield, Tracey L.
Sutton, Morgan T.
Fletcher, David R.
Reese-Koc, Jane
Roesch, Erica A.
Lazarus, Hillard M.
Chmiel, James F.
Caplan, Arnold I.
author_facet Bonfield, Tracey L.
Sutton, Morgan T.
Fletcher, David R.
Reese-Koc, Jane
Roesch, Erica A.
Lazarus, Hillard M.
Chmiel, James F.
Caplan, Arnold I.
author_sort Bonfield, Tracey L.
collection PubMed
description Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. The application of hMSC immunotherapy to the CF clinical armamentarium is important even in the era of modulators when patients with an established disease still need anti-inflammatory and anti-microbial therapies. Additionally, people with CF mutations not addressed by current modulator resources need anti-inflammation and anti-infection management. Furthermore, hMSCs possess dynamic therapeutic properties, but the potency of their products is highly variable with respect to their anti-inflammatory and anti-microbial effects. Due to the variability of hMSC products, we utilized standardized in vitro and in vivo models to select hMSC donor preparations with the greatest potential for clinical efficacy. The models that were used recapitulate many of the pathophysiologic outcomes associated with CF. We applied this strategy in pursuit of identifying the optimal donor to utilize for the “First in CF” Phase I clinical trial of hMSCs as an immunotherapy and anti-microbial therapy for people with cystic fibrosis. The hMSCs screened in this study demonstrated significant diversity in antimicrobial and anti-inflammatory function using models which mimic some aspects of CF infection and inflammation. However, the variability in activity between in vitro potency and in vivo effectiveness continues to be refined. Future studies require and in-depth pursuit of hMSC molecular signatures that ultimately predict the capacity of hMSCs to function in the clinical setting.
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spelling pubmed-99607672023-02-26 Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF) Bonfield, Tracey L. Sutton, Morgan T. Fletcher, David R. Reese-Koc, Jane Roesch, Erica A. Lazarus, Hillard M. Chmiel, James F. Caplan, Arnold I. Pharmaceuticals (Basel) Article Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. The application of hMSC immunotherapy to the CF clinical armamentarium is important even in the era of modulators when patients with an established disease still need anti-inflammatory and anti-microbial therapies. Additionally, people with CF mutations not addressed by current modulator resources need anti-inflammation and anti-infection management. Furthermore, hMSCs possess dynamic therapeutic properties, but the potency of their products is highly variable with respect to their anti-inflammatory and anti-microbial effects. Due to the variability of hMSC products, we utilized standardized in vitro and in vivo models to select hMSC donor preparations with the greatest potential for clinical efficacy. The models that were used recapitulate many of the pathophysiologic outcomes associated with CF. We applied this strategy in pursuit of identifying the optimal donor to utilize for the “First in CF” Phase I clinical trial of hMSCs as an immunotherapy and anti-microbial therapy for people with cystic fibrosis. The hMSCs screened in this study demonstrated significant diversity in antimicrobial and anti-inflammatory function using models which mimic some aspects of CF infection and inflammation. However, the variability in activity between in vitro potency and in vivo effectiveness continues to be refined. Future studies require and in-depth pursuit of hMSC molecular signatures that ultimately predict the capacity of hMSCs to function in the clinical setting. MDPI 2023-02-01 /pmc/articles/PMC9960767/ /pubmed/37259368 http://dx.doi.org/10.3390/ph16020220 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bonfield, Tracey L.
Sutton, Morgan T.
Fletcher, David R.
Reese-Koc, Jane
Roesch, Erica A.
Lazarus, Hillard M.
Chmiel, James F.
Caplan, Arnold I.
Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
title Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
title_full Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
title_fullStr Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
title_full_unstemmed Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
title_short Human Mesenchymal Stem Cell (hMSC) Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
title_sort human mesenchymal stem cell (hmsc) donor potency selection for the “first in cystic fibrosis” phase i clinical trial (cease-cf)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960767/
https://www.ncbi.nlm.nih.gov/pubmed/37259368
http://dx.doi.org/10.3390/ph16020220
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