A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation

Background: Bone marrow-derived mesenchymal stromal cells (BMSCs) are a cell population of intense exploration for therapeutic use in inflammatory diseases. Secreted factors released by BMSCs are responsible for the resolution of inflammation in several pre-clinical models. New studies have uncover...

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Main Authors: Elman, Jessica S, Li, Matthew, Wang, Fangjing, Gimble, Jeffrey M, Parekkadan, Biju
Other Authors: Whitaker College of Health Sciences and Technology
Format: Article
Language:English
Published: BioMed Central Ltd 2014
Online Access:http://hdl.handle.net/1721.1/84099
https://orcid.org/0000-0001-9296-2220
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author Elman, Jessica S
Li, Matthew
Wang, Fangjing
Gimble, Jeffrey M
Parekkadan, Biju
author2 Whitaker College of Health Sciences and Technology
author_facet Whitaker College of Health Sciences and Technology
Elman, Jessica S
Li, Matthew
Wang, Fangjing
Gimble, Jeffrey M
Parekkadan, Biju
author_sort Elman, Jessica S
collection MIT
description Background: Bone marrow-derived mesenchymal stromal cells (BMSCs) are a cell population of intense exploration for therapeutic use in inflammatory diseases. Secreted factors released by BMSCs are responsible for the resolution of inflammation in several pre-clinical models. New studies have uncovered that adipose tissue also serves as a reservoir of multipotent, non-hematopoietic stem cells, termed adipose-derived stromal/stem cells (ASCs), with many common characteristics to BMSCs. We hypothesized that ASC and BMSC secreted factors would lead to a comparable benefit in the context of generalized inflammation. Findings: Proteomic profiling of conditioned media revealed that BMSCs express significantly higher levels of sVEGFR1 and sTNFR1, two soluble cytokine receptors with known therapeutic activity in sepsis. In a prophylactic study of endotoxin-induced inflammation in mice, we observed that BMSC secreted factors provided a greater survival benefit and tissue protection of endotoxemic mice compared to ASCs. Neutralization of sVEGFR1 and sTNFR1 did not significantly affect the survival benefit experienced by mice treated with BMSC secreted factors. Conclusions: Our findings suggest that BMSCs may be more effective as a cell therapeutic for use in endotoxic shock and that ASCs may be positioned for continued exploration in immunomodulatory diseases. Soluble cytokine receptors can distinguish stromal cells from different tissue origins, though they may not be the sole contributors to the therapeutic benefit of BMSCs. Furthermore, other secreted factors not discussed in this study may also differentiate these stromal cell populations from one another.
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spelling mit-1721.1/840992022-09-28T00:51:02Z A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation Elman, Jessica S Li, Matthew Wang, Fangjing Gimble, Jeffrey M Parekkadan, Biju Whitaker College of Health Sciences and Technology Harvard University--MIT Division of Health Sciences and Technology Li, Matthew Background: Bone marrow-derived mesenchymal stromal cells (BMSCs) are a cell population of intense exploration for therapeutic use in inflammatory diseases. Secreted factors released by BMSCs are responsible for the resolution of inflammation in several pre-clinical models. New studies have uncovered that adipose tissue also serves as a reservoir of multipotent, non-hematopoietic stem cells, termed adipose-derived stromal/stem cells (ASCs), with many common characteristics to BMSCs. We hypothesized that ASC and BMSC secreted factors would lead to a comparable benefit in the context of generalized inflammation. Findings: Proteomic profiling of conditioned media revealed that BMSCs express significantly higher levels of sVEGFR1 and sTNFR1, two soluble cytokine receptors with known therapeutic activity in sepsis. In a prophylactic study of endotoxin-induced inflammation in mice, we observed that BMSC secreted factors provided a greater survival benefit and tissue protection of endotoxemic mice compared to ASCs. Neutralization of sVEGFR1 and sTNFR1 did not significantly affect the survival benefit experienced by mice treated with BMSC secreted factors. Conclusions: Our findings suggest that BMSCs may be more effective as a cell therapeutic for use in endotoxic shock and that ASCs may be positioned for continued exploration in immunomodulatory diseases. Soluble cytokine receptors can distinguish stromal cells from different tissue origins, though they may not be the sole contributors to the therapeutic benefit of BMSCs. Furthermore, other secreted factors not discussed in this study may also differentiate these stromal cell populations from one another. National Institutes of Health (U.S.) (R01EB012521) National Institutes of Health (U.S.) (K01DK087770) Broad Foundations (Broad Medical Research Program BMRP498382) Shriners Hospital for Children 2014-01-21T16:50:57Z 2014-01-21T16:50:57Z 2014-01 2012-11 2014-01-09T12:48:05Z Article http://purl.org/eprint/type/JournalArticle 1476-9255 http://hdl.handle.net/1721.1/84099 Elman, Jessica S et al. “A Comparison of Adipose and Bone Marrow-Derived Mesenchymal Stromal Cell Secreted Factors in the Treatment of Systemic Inflammation.” Journal of Inflammation 11.1 (2014): 1. https://orcid.org/0000-0001-9296-2220 en http://dx.doi.org/10.1186/1476-9255-11-1 Journal of Inflammation Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Jessica S Elman et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd
spellingShingle Elman, Jessica S
Li, Matthew
Wang, Fangjing
Gimble, Jeffrey M
Parekkadan, Biju
A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
title A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
title_full A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
title_fullStr A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
title_full_unstemmed A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
title_short A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
title_sort comparison of adipose and bone marrow derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
url http://hdl.handle.net/1721.1/84099
https://orcid.org/0000-0001-9296-2220
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