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Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy
BACKGROUND: Endothelial dysfunction contributes to the pathophysiology of dilated cardiomyopathy (DCM). Allogeneic but not autologous mesenchymal stem cells (MSCs) improve endothelial function in DCM patients. We hypothesized that these effects are modulated by release of stromal derived factor-1α (...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769040/ https://www.ncbi.nlm.nih.gov/pubmed/31616309 http://dx.doi.org/10.3389/fphys.2019.01182 |
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author | Premer, Courtney Wanschel, Amarylis Porras, Valeria Balkan, Wayne Legendre-Hyldig, Tatiana Saltzman, Russell G. Dong, Chunming Schulman, Ivonne Hernandez Hare, Joshua M. |
author_facet | Premer, Courtney Wanschel, Amarylis Porras, Valeria Balkan, Wayne Legendre-Hyldig, Tatiana Saltzman, Russell G. Dong, Chunming Schulman, Ivonne Hernandez Hare, Joshua M. |
author_sort | Premer, Courtney |
collection | PubMed |
description | BACKGROUND: Endothelial dysfunction contributes to the pathophysiology of dilated cardiomyopathy (DCM). Allogeneic but not autologous mesenchymal stem cells (MSCs) improve endothelial function in DCM patients. We hypothesized that these effects are modulated by release of stromal derived factor-1α (SDF-1α). METHODS: Plasma TNFα and endothelial progenitor cell-colony forming units (EPC-CFUs) were assessed at baseline and 3-months post-injection in a subset of POSEIDON-DCM patients that received autologous (n = 11) or allogeneic (n = 10) MSCs. SDF-1α secretion by MSCs, endothelial cell (EC) TNFα mRNA expression, and levels of reactive oxygen species (ROS) in response to SDF-1α were measured in vitro. RESULTS: As previously shown, DCM patients (n = 21) had reduced EPC-CFUs at baseline (3 ± 3), which were restored to normal by allogeneic MSCs 3-months post-treatment (Δ10 ± 4). DCM patients had elevated baseline plasma TNFα (n = 15, 22 ± 9.4 pg/mL). Allogeneic MSCs (n = 8) decreased, and autologous MSCs (n = 7) increased, plasma TNFα (−7.1 ± 3.1 vs. 22.2 ± 17.1 pg/mL, respectively; P = 0.0005). In culture, autologous MSCs (n = 11) secreted higher levels of SDF-1α than allogeneic MSCs (n = 6) [76.0 (63.7, 100.9) vs. 22.8 (7.2, 43.5) pg/mL, P = 0.0002]. SDF-1α and plasma TNFα negatively correlated with EPC-CFUs in both treatment groups (R = −0.7, P = 0.0004). ECs treated with 20 ng SDF-1α expressed lower levels of TNFα mRNA than cells treated with 100 ng (0.7 ± 0.2 vs. 2.1 ± 0.3, P = 0.0008). SDF-1α at low but not high concentration inhibited the generation of ROS. CONCLUSION: MSC secretion of SDF-1α inversely correlates with EPC-CFU production in DCM patients and therefore may be a modulator of MSC therapeutic effect in this clinical setting. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01392625, identifier NCT01392625. |
format | Online Article Text |
id | pubmed-6769040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67690402019-10-15 Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy Premer, Courtney Wanschel, Amarylis Porras, Valeria Balkan, Wayne Legendre-Hyldig, Tatiana Saltzman, Russell G. Dong, Chunming Schulman, Ivonne Hernandez Hare, Joshua M. Front Physiol Physiology BACKGROUND: Endothelial dysfunction contributes to the pathophysiology of dilated cardiomyopathy (DCM). Allogeneic but not autologous mesenchymal stem cells (MSCs) improve endothelial function in DCM patients. We hypothesized that these effects are modulated by release of stromal derived factor-1α (SDF-1α). METHODS: Plasma TNFα and endothelial progenitor cell-colony forming units (EPC-CFUs) were assessed at baseline and 3-months post-injection in a subset of POSEIDON-DCM patients that received autologous (n = 11) or allogeneic (n = 10) MSCs. SDF-1α secretion by MSCs, endothelial cell (EC) TNFα mRNA expression, and levels of reactive oxygen species (ROS) in response to SDF-1α were measured in vitro. RESULTS: As previously shown, DCM patients (n = 21) had reduced EPC-CFUs at baseline (3 ± 3), which were restored to normal by allogeneic MSCs 3-months post-treatment (Δ10 ± 4). DCM patients had elevated baseline plasma TNFα (n = 15, 22 ± 9.4 pg/mL). Allogeneic MSCs (n = 8) decreased, and autologous MSCs (n = 7) increased, plasma TNFα (−7.1 ± 3.1 vs. 22.2 ± 17.1 pg/mL, respectively; P = 0.0005). In culture, autologous MSCs (n = 11) secreted higher levels of SDF-1α than allogeneic MSCs (n = 6) [76.0 (63.7, 100.9) vs. 22.8 (7.2, 43.5) pg/mL, P = 0.0002]. SDF-1α and plasma TNFα negatively correlated with EPC-CFUs in both treatment groups (R = −0.7, P = 0.0004). ECs treated with 20 ng SDF-1α expressed lower levels of TNFα mRNA than cells treated with 100 ng (0.7 ± 0.2 vs. 2.1 ± 0.3, P = 0.0008). SDF-1α at low but not high concentration inhibited the generation of ROS. CONCLUSION: MSC secretion of SDF-1α inversely correlates with EPC-CFU production in DCM patients and therefore may be a modulator of MSC therapeutic effect in this clinical setting. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01392625, identifier NCT01392625. Frontiers Media S.A. 2019-09-24 /pmc/articles/PMC6769040/ /pubmed/31616309 http://dx.doi.org/10.3389/fphys.2019.01182 Text en Copyright © 2019 Premer, Wanschel, Porras, Balkan, Legendre-Hyldig, Saltzman, Dong, Schulman and Hare. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Premer, Courtney Wanschel, Amarylis Porras, Valeria Balkan, Wayne Legendre-Hyldig, Tatiana Saltzman, Russell G. Dong, Chunming Schulman, Ivonne Hernandez Hare, Joshua M. Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy |
title | Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy |
title_full | Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy |
title_fullStr | Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy |
title_full_unstemmed | Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy |
title_short | Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy |
title_sort | mesenchymal stem cell secretion of sdf-1α modulates endothelial function in dilated cardiomyopathy |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769040/ https://www.ncbi.nlm.nih.gov/pubmed/31616309 http://dx.doi.org/10.3389/fphys.2019.01182 |
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