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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...

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Autores principales: Boregowda, Siddaraju V., Krishnappa, Veena, Haga, Christopher L., Ortiz, Luis A., Phinney, Donald G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
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.
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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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