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...
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Autor*in:	Xiaoyin Wang [verfasserIn] Lourdes I Chacon [verfasserIn] Ronak Derakhshandeh [verfasserIn] Hilda J Rodriguez [verfasserIn] Daniel D Han [verfasserIn] Dmitry S Kostyushev [verfasserIn] Timothy D Henry [verfasserIn] Jay H Traverse [verfasserIn] Lem Moyé [verfasserIn] Robert D Simari [verfasserIn] Doris A Taylor [verfasserIn] Matthew L Springer [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 15(2020), 8, p e0237401
Übergeordnetes Werk:	volume:15 ; year:2020 ; number:8, p e0237401

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0237401

Katalog-ID:	DOAJ025086790

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allfields	10.1371/journal.pone.0237401 doi (DE-627)DOAJ025086790 (DE-599)DOAJbde7957cd334448b901ef20c8549a427 DE-627 ger DE-627 rakwb eng Xiaoyin Wang verfasserin aut Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials. 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Lourdes I Chacon verfasserin aut Ronak Derakhshandeh verfasserin aut Hilda J Rodriguez verfasserin aut Daniel D Han verfasserin aut Dmitry S Kostyushev verfasserin aut Timothy D Henry verfasserin aut Jay H Traverse verfasserin aut Lem Moyé verfasserin aut Robert D Simari verfasserin aut Doris A Taylor verfasserin aut Matthew L Springer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 15(2020), 8, p e0237401 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:15 year:2020 number:8, p e0237401 https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/article/bde7957cd334448b901ef20c8549a427 kostenfrei https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2020 8, p e0237401
spelling	10.1371/journal.pone.0237401 doi (DE-627)DOAJ025086790 (DE-599)DOAJbde7957cd334448b901ef20c8549a427 DE-627 ger DE-627 rakwb eng Xiaoyin Wang verfasserin aut Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials. 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Lourdes I Chacon verfasserin aut Ronak Derakhshandeh verfasserin aut Hilda J Rodriguez verfasserin aut Daniel D Han verfasserin aut Dmitry S Kostyushev verfasserin aut Timothy D Henry verfasserin aut Jay H Traverse verfasserin aut Lem Moyé verfasserin aut Robert D Simari verfasserin aut Doris A Taylor verfasserin aut Matthew L Springer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 15(2020), 8, p e0237401 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:15 year:2020 number:8, p e0237401 https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/article/bde7957cd334448b901ef20c8549a427 kostenfrei https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2020 8, p e0237401
allfields_unstemmed	10.1371/journal.pone.0237401 doi (DE-627)DOAJ025086790 (DE-599)DOAJbde7957cd334448b901ef20c8549a427 DE-627 ger DE-627 rakwb eng Xiaoyin Wang verfasserin aut Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials. 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Lourdes I Chacon verfasserin aut Ronak Derakhshandeh verfasserin aut Hilda J Rodriguez verfasserin aut Daniel D Han verfasserin aut Dmitry S Kostyushev verfasserin aut Timothy D Henry verfasserin aut Jay H Traverse verfasserin aut Lem Moyé verfasserin aut Robert D Simari verfasserin aut Doris A Taylor verfasserin aut Matthew L Springer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 15(2020), 8, p e0237401 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:15 year:2020 number:8, p e0237401 https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/article/bde7957cd334448b901ef20c8549a427 kostenfrei https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2020 8, p e0237401
allfieldsGer	10.1371/journal.pone.0237401 doi (DE-627)DOAJ025086790 (DE-599)DOAJbde7957cd334448b901ef20c8549a427 DE-627 ger DE-627 rakwb eng Xiaoyin Wang verfasserin aut Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials. 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Lourdes I Chacon verfasserin aut Ronak Derakhshandeh verfasserin aut Hilda J Rodriguez verfasserin aut Daniel D Han verfasserin aut Dmitry S Kostyushev verfasserin aut Timothy D Henry verfasserin aut Jay H Traverse verfasserin aut Lem Moyé verfasserin aut Robert D Simari verfasserin aut Doris A Taylor verfasserin aut Matthew L Springer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 15(2020), 8, p e0237401 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:15 year:2020 number:8, p e0237401 https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/article/bde7957cd334448b901ef20c8549a427 kostenfrei https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2020 8, p e0237401
allfieldsSound	10.1371/journal.pone.0237401 doi (DE-627)DOAJ025086790 (DE-599)DOAJbde7957cd334448b901ef20c8549a427 DE-627 ger DE-627 rakwb eng Xiaoyin Wang verfasserin aut Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials. 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Science Q Lourdes I Chacon verfasserin aut Ronak Derakhshandeh verfasserin aut Hilda J Rodriguez verfasserin aut Daniel D Han verfasserin aut Dmitry S Kostyushev verfasserin aut Timothy D Henry verfasserin aut Jay H Traverse verfasserin aut Lem Moyé verfasserin aut Robert D Simari verfasserin aut Doris A Taylor verfasserin aut Matthew L Springer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 15(2020), 8, p e0237401 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:15 year:2020 number:8, p e0237401 https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/article/bde7957cd334448b901ef20c8549a427 kostenfrei https://doi.org/10.1371/journal.pone.0237401 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2020 8, p e0237401
language	English
source	In PLoS ONE 15(2020), 8, p e0237401 volume:15 year:2020 number:8, p e0237401
sourceStr	In PLoS ONE 15(2020), 8, p e0237401 volume:15 year:2020 number:8, p e0237401
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
isfreeaccess_bool	true
container_title	PLoS ONE
authorswithroles_txt_mv	Xiaoyin Wang @@aut@@ Lourdes I Chacon @@aut@@ Ronak Derakhshandeh @@aut@@ Hilda J Rodriguez @@aut@@ Daniel D Han @@aut@@ Dmitry S Kostyushev @@aut@@ Timothy D Henry @@aut@@ Jay H Traverse @@aut@@ Lem Moyé @@aut@@ Robert D Simari @@aut@@ Doris A Taylor @@aut@@ Matthew L Springer @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	523574592
id	DOAJ025086790
language_de	englisch
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author	Xiaoyin Wang
spellingShingle	Xiaoyin Wang misc Medicine misc R misc Science misc Q Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials.
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topic_title	Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
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title	Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials.
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title_full	Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials
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author_browse	Xiaoyin Wang Lourdes I Chacon Ronak Derakhshandeh Hilda J Rodriguez Daniel D Han Dmitry S Kostyushev Timothy D Henry Jay H Traverse Lem Moyé Robert D Simari Doris A Taylor Matthew L Springer
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title_sort	impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the time and latetime clinical trials
title_auth	Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials.
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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials.
url	https://doi.org/10.1371/journal.pone.0237401 https://doaj.org/article/bde7957cd334448b901ef20c8549a427 https://doaj.org/toc/1932-6203
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up_date	2024-07-04T01:32:22.060Z
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Impaired therapeutic efficacy of bone marrow cells from post-myocardial infarction patients in the TIME and LateTIME clinical trials.

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