Open Access
PLoS ONE, volume 15, issue 8, pages e0237401
Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
Wang Xiaoyin
1
,
Chacon Lourdes I
2
,
Derakhshandeh Ronak
1
,
Rodriguez Hilda J.
3
,
Han Daniel D.
4
,
Henry Timothy D.
5
,
Traverse Jay H.
6
,
Moyé Lem
7
,
Simari Robert D.
8
,
Taylor Doris A
2
,
Springer Matthew L.
9
1
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, United States of America
|
2
Texas Heart Institute, Houston, TX, United States of America
|
3
Division of Cardiology, University of California, San Francisco, San Francisco, CA, United States of America,
|
4
Division of Cardiology, University of California, San Francisco, San Francisco, CA, United States of America
|
5
The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital, Cincinnati, OH, United States of America
|
6
Minneapolis Heart Institute Foundation, Minneapolis, MN, United States of America
|
7
University of Texas Health School of Public Health, Houston, TX, United States of America
|
8
Kansas University Medical Center, Kansas City, KS, United States of America
|
9
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, United States of America,
|
Publication type: Journal Article
Publication date: 2020-08-25
PubMed ID:
32841277
Multidisciplinary
Abstract
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.
Citations by journals
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1
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Frontiers in Bioengineering and Biotechnology
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Frontiers in Bioengineering and Biotechnology
1 publication, 50%
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Cardiovascular Research
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Cardiovascular Research
1 publication, 50%
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1
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Citations by publishers
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1
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Frontiers Media S.A.
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Frontiers Media S.A.
1 publication, 50%
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Oxford University Press
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Oxford University Press
1 publication, 50%
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1
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Wang X. et al. Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials // PLoS ONE. 2020. Vol. 15. No. 8. p. e0237401.
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Wang X., Chacon L. I., Derakhshandeh R., Rodriguez H. J., Han D. D., Kostyushev D., Henry T. D., Traverse J. H., Moyé L., Simari R. D., Taylor D. A., Springer M. L. Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials // PLoS ONE. 2020. Vol. 15. No. 8. p. e0237401.
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TY - JOUR
DO - 10.1371/journal.pone.0237401
UR - https://doi.org/10.1371%2Fjournal.pone.0237401
TI - Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
T2 - PLoS ONE
AU - Wang, Xiaoyin
AU - Chacon, Lourdes I
AU - Derakhshandeh, Ronak
AU - Rodriguez, Hilda J.
AU - Han, Daniel D.
AU - Kostyushev, Dmitry
AU - Henry, Timothy D.
AU - Traverse, Jay H.
AU - Moyé, Lem
AU - Simari, Robert D.
AU - Taylor, Doris A
AU - Springer, Matthew L.
PY - 2020
DA - 2020/08/25 00:00:00
PB - Public Library of Science (PLoS)
SP - e0237401
IS - 8
VL - 15
PMID - 32841277
SN - 1932-6203
ER -
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@article{2020_Wang,
author = {Xiaoyin Wang and Lourdes I Chacon and Ronak Derakhshandeh and Hilda J. Rodriguez and Daniel D. Han and Dmitry Kostyushev and Timothy D. Henry and Jay H. Traverse and Lem Moyé and Robert D. Simari and Doris A Taylor and Matthew L. Springer},
title = {Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials},
journal = {PLoS ONE},
year = {2020},
volume = {15},
publisher = {Public Library of Science (PLoS)},
month = {aug},
url = {https://doi.org/10.1371%2Fjournal.pone.0237401},
number = {8},
pages = {e0237401},
doi = {10.1371/journal.pone.0237401}
}
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MLA
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Wang, Xiaoyin, et al. “Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials.” PLoS ONE, vol. 15, no. 8, Aug. 2020, p. e0237401. https://doi.org/10.1371%2Fjournal.pone.0237401.