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A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells
In addition to their stem/progenitor properties, mesenchymal stem cells (MSCs) also exhibit potent effector (angiogenic, antiinflammatory, immuno-modulatory) functions that are largely paracrine in nature. It is widely believed that effector functions underlie most of the therapeutic potential of MS...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776067/ https://www.ncbi.nlm.nih.gov/pubmed/26981553 http://dx.doi.org/10.1016/j.ebiom.2015.12.020 |
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author | Boregowda, Siddaraju V. Krishnappa, Veena Haga, Christopher L. Ortiz, Luis A. Phinney, Donald G. |
author_facet | Boregowda, Siddaraju V. Krishnappa, Veena Haga, Christopher L. Ortiz, Luis A. Phinney, Donald G. |
author_sort | Boregowda, Siddaraju V. |
collection | PubMed |
description | In addition to their stem/progenitor properties, mesenchymal stem cells (MSCs) also exhibit potent effector (angiogenic, antiinflammatory, immuno-modulatory) functions that are largely paracrine in nature. It is widely believed that effector functions underlie most of the therapeutic potential of MSCs and are independent of their stem/progenitor properties. Here we demonstrate that stem/progenitor and effector functions are coordinately regulated at the cellular level by the transcription factor Twist1 and specified within populations according to a hierarchical model. We further show that manipulation of Twist1 levels by genetic approaches or by exposure to widely used culture supplements including fibroblast growth factor 2 (Ffg2) and interferon gamma (IFN-gamma) alters MSC efficacy in cell-based and in vivo assays in a predictable manner. Thus, by mechanistically linking stem/progenitor and effector functions our studies provide a unifying framework in the form of an MSC hierarchy that models the functional complexity of populations. Using this framework, we developed a CLinical Indications Prediction (CLIP) scale that predicts how donor-to-donor heterogeneity and culture conditions impact the therapeutic efficacy of MSC populations for different disease indications. |
format | Online Article Text |
id | pubmed-4776067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-47760672016-03-15 A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells Boregowda, Siddaraju V. Krishnappa, Veena Haga, Christopher L. Ortiz, Luis A. Phinney, Donald G. EBioMedicine Research Paper In addition to their stem/progenitor properties, mesenchymal stem cells (MSCs) also exhibit potent effector (angiogenic, antiinflammatory, immuno-modulatory) functions that are largely paracrine in nature. It is widely believed that effector functions underlie most of the therapeutic potential of MSCs and are independent of their stem/progenitor properties. Here we demonstrate that stem/progenitor and effector functions are coordinately regulated at the cellular level by the transcription factor Twist1 and specified within populations according to a hierarchical model. We further show that manipulation of Twist1 levels by genetic approaches or by exposure to widely used culture supplements including fibroblast growth factor 2 (Ffg2) and interferon gamma (IFN-gamma) alters MSC efficacy in cell-based and in vivo assays in a predictable manner. Thus, by mechanistically linking stem/progenitor and effector functions our studies provide a unifying framework in the form of an MSC hierarchy that models the functional complexity of populations. Using this framework, we developed a CLinical Indications Prediction (CLIP) scale that predicts how donor-to-donor heterogeneity and culture conditions impact the therapeutic efficacy of MSC populations for different disease indications. Elsevier 2015-12-24 /pmc/articles/PMC4776067/ /pubmed/26981553 http://dx.doi.org/10.1016/j.ebiom.2015.12.020 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Boregowda, Siddaraju V. Krishnappa, Veena Haga, Christopher L. Ortiz, Luis A. Phinney, Donald G. A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells |
title | A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells |
title_full | A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells |
title_fullStr | A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells |
title_full_unstemmed | A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells |
title_short | A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells |
title_sort | clinical indications prediction scale based on twist1 for human mesenchymal stem cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776067/ https://www.ncbi.nlm.nih.gov/pubmed/26981553 http://dx.doi.org/10.1016/j.ebiom.2015.12.020 |
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