Cargando…

Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials

Implantation of bone marrow-derived cells (BMCs) into mouse hearts post-myocardial infarction (MI) limits cardiac functional decline. However, clinical trials of post-MI BMC therapy have yielded conflicting results. While most laboratory experiments use healthy BMC donor mice, clinical trials use po...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xiaoyin, Chacon, Lourdes I., Derakhshandeh, Ronak, Rodriguez, Hilda J., Han, Daniel D., Kostyushev, Dmitry S., Henry, Timothy D., Traverse, Jay H., Moyé, Lem, Simari, Robert D., Taylor, Doris A., Springer, Matthew L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446972/
https://www.ncbi.nlm.nih.gov/pubmed/32841277
http://dx.doi.org/10.1371/journal.pone.0237401
_version_ 1783574223031107584
author Wang, Xiaoyin
Chacon, Lourdes I.
Derakhshandeh, Ronak
Rodriguez, Hilda J.
Han, Daniel D.
Kostyushev, Dmitry S.
Henry, Timothy D.
Traverse, Jay H.
Moyé, Lem
Simari, Robert D.
Taylor, Doris A.
Springer, Matthew L.
author_facet Wang, Xiaoyin
Chacon, Lourdes I.
Derakhshandeh, Ronak
Rodriguez, Hilda J.
Han, Daniel D.
Kostyushev, Dmitry S.
Henry, Timothy D.
Traverse, Jay H.
Moyé, Lem
Simari, Robert D.
Taylor, Doris A.
Springer, Matthew L.
author_sort Wang, Xiaoyin
collection PubMed
description Implantation of bone marrow-derived cells (BMCs) into mouse hearts post-myocardial infarction (MI) limits cardiac functional decline. However, clinical trials of post-MI BMC therapy have yielded conflicting results. While most laboratory experiments use healthy BMC donor mice, clinical trials use post-MI autologous BMCs. Post-MI mouse BMCs are therapeutically impaired, due to inflammatory changes in BMC composition. Thus, therapeutic efficacy of the BMCs progressively worsens after MI but recovers as donor inflammatory response resolves. The availability of post-MI patient BM mononuclear cells (MNCs) from the TIME and LateTIME clinical trials enabled us to test if human post-MI MNCs undergo a similar period of impaired efficacy. We hypothesized that MNCs from TIME trial patients would be less therapeutic than healthy human donor MNCs when implanted into post-MI mouse hearts, and that therapeutic properties would be restored in MNCs from LateTIME trial patients. Post-MI SCID mice received MNCs from healthy donors, TIME patients, or LateTIME patients. Cardiac function improved considerably in the healthy donor group, but neither the TIME nor LateTIME group showed therapeutic effect. Conclusion: post-MI human MNCs lack therapeutic benefits possessed by healthy MNCs, which may partially explain why BMC clinical trials have been less successful than mouse studies.
format Online
Article
Text
id pubmed-7446972
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-74469722020-08-31 Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials Wang, Xiaoyin Chacon, Lourdes I. Derakhshandeh, Ronak Rodriguez, Hilda J. Han, Daniel D. Kostyushev, Dmitry S. Henry, Timothy D. Traverse, Jay H. Moyé, Lem Simari, Robert D. Taylor, Doris A. Springer, Matthew L. PLoS One Research Article Implantation of bone marrow-derived cells (BMCs) into mouse hearts post-myocardial infarction (MI) limits cardiac functional decline. However, clinical trials of post-MI BMC therapy have yielded conflicting results. While most laboratory experiments use healthy BMC donor mice, clinical trials use post-MI autologous BMCs. Post-MI mouse BMCs are therapeutically impaired, due to inflammatory changes in BMC composition. Thus, therapeutic efficacy of the BMCs progressively worsens after MI but recovers as donor inflammatory response resolves. The availability of post-MI patient BM mononuclear cells (MNCs) from the TIME and LateTIME clinical trials enabled us to test if human post-MI MNCs undergo a similar period of impaired efficacy. We hypothesized that MNCs from TIME trial patients would be less therapeutic than healthy human donor MNCs when implanted into post-MI mouse hearts, and that therapeutic properties would be restored in MNCs from LateTIME trial patients. Post-MI SCID mice received MNCs from healthy donors, TIME patients, or LateTIME patients. Cardiac function improved considerably in the healthy donor group, but neither the TIME nor LateTIME group showed therapeutic effect. Conclusion: post-MI human MNCs lack therapeutic benefits possessed by healthy MNCs, which may partially explain why BMC clinical trials have been less successful than mouse studies. Public Library of Science 2020-08-25 /pmc/articles/PMC7446972/ /pubmed/32841277 http://dx.doi.org/10.1371/journal.pone.0237401 Text en © 2020 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Xiaoyin
Chacon, Lourdes I.
Derakhshandeh, Ronak
Rodriguez, Hilda J.
Han, Daniel D.
Kostyushev, Dmitry S.
Henry, Timothy D.
Traverse, Jay H.
Moyé, Lem
Simari, Robert D.
Taylor, Doris A.
Springer, Matthew L.
Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
title Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
title_full Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
title_fullStr Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
title_full_unstemmed Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
title_short Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
title_sort impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the time and latetime clinical trials
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446972/
https://www.ncbi.nlm.nih.gov/pubmed/32841277
http://dx.doi.org/10.1371/journal.pone.0237401
work_keys_str_mv AT wangxiaoyin impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT chaconlourdesi impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT derakhshandehronak impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT rodriguezhildaj impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT handanield impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT kostyushevdmitrys impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT henrytimothyd impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT traversejayh impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT moyelem impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT simarirobertd impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT taylordorisa impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials
AT springermatthewl impairedtherapeuticefficacyofbonemarrowcellsfrompostmyocardialinfarctionpatientsinthetimeandlatetimeclinicaltrials