Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury

There is no effective treatment for the total recovery of myocardial injury caused by an anticancer drug, doxorubicin (Dox). In this study, using a Dox-induced cardiac injury model, we compared the cardioprotective effects of ventricular cells harvested from 11.5-day old embryonic mice (E11.5) with...

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Autores principales: Mark Baguma-Nibasheka, Tiam Feridooni, Feixiong Zhang, Kishore B.S. Pasumarthi
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:405a832b3dc947d2acd71feb9324bc7b2021-11-25T17:10:15ZRegulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury10.3390/cells101129982073-4409https://doaj.org/article/405a832b3dc947d2acd71feb9324bc7b2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2998https://doaj.org/toc/2073-4409There is no effective treatment for the total recovery of myocardial injury caused by an anticancer drug, doxorubicin (Dox). In this study, using a Dox-induced cardiac injury model, we compared the cardioprotective effects of ventricular cells harvested from 11.5-day old embryonic mice (E11.5) with those from E14.5 embryos. Our results indicate that tail-vein-infused E11.5 ventricular cells are more efficient at homing into the injured adult myocardium, and are more angiogenic, than E14.5 ventricular cells. In addition, E11.5 cells were shown to mitigate the cardiomyopathic effects of Dox. In vitro, E11.5 ventricular cells were more migratory than E14.5 cells, and RT-qPCR analysis revealed that they express significantly higher levels of cytokine receptors <i>Fgfr1</i>, <i>Fgfr2</i>, <i>Pdgfra</i>, <i>Pdgfrb</i> and <i>Kit</i>. Remarkably, mRNA levels for <i>Fgf1, Fgf2, Pdgfa</i> and <i>Pdgfb</i> were also found to be elevated in the Dox-injured adult heart, as were the FGF1 and PDGFB protein levels. Addition of exogenous FGF1 or PDGFB was able to enhance E11.5 ventricular cell migration in vitro, and, whereas their neutralizing antibodies decreased cell migration. These results indicate that therapies raising the levels of FGF1 and PDGFB receptors in donor cells and or corresponding ligands in an injured heart could improve the efficacy of cell-based interventions for myocardial repair.Mark Baguma-NibashekaTiam FeridooniFeixiong ZhangKishore B.S. PasumarthiMDPI AGarticleventricular cell migrationgrowth factor and chemokine receptorsdoxorubicincardiomyopathycardiac dysfunctionBiology (General)QH301-705.5ENCells, Vol 10, Iss 2998, p 2998 (2021)
institution DOAJ
collection DOAJ
language EN
topic ventricular cell migration
growth factor and chemokine receptors
doxorubicin
cardiomyopathy
cardiac dysfunction
Biology (General)
QH301-705.5
spellingShingle ventricular cell migration
growth factor and chemokine receptors
doxorubicin
cardiomyopathy
cardiac dysfunction
Biology (General)
QH301-705.5
Mark Baguma-Nibasheka
Tiam Feridooni
Feixiong Zhang
Kishore B.S. Pasumarthi
Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury
description There is no effective treatment for the total recovery of myocardial injury caused by an anticancer drug, doxorubicin (Dox). In this study, using a Dox-induced cardiac injury model, we compared the cardioprotective effects of ventricular cells harvested from 11.5-day old embryonic mice (E11.5) with those from E14.5 embryos. Our results indicate that tail-vein-infused E11.5 ventricular cells are more efficient at homing into the injured adult myocardium, and are more angiogenic, than E14.5 ventricular cells. In addition, E11.5 cells were shown to mitigate the cardiomyopathic effects of Dox. In vitro, E11.5 ventricular cells were more migratory than E14.5 cells, and RT-qPCR analysis revealed that they express significantly higher levels of cytokine receptors <i>Fgfr1</i>, <i>Fgfr2</i>, <i>Pdgfra</i>, <i>Pdgfrb</i> and <i>Kit</i>. Remarkably, mRNA levels for <i>Fgf1, Fgf2, Pdgfa</i> and <i>Pdgfb</i> were also found to be elevated in the Dox-injured adult heart, as were the FGF1 and PDGFB protein levels. Addition of exogenous FGF1 or PDGFB was able to enhance E11.5 ventricular cell migration in vitro, and, whereas their neutralizing antibodies decreased cell migration. These results indicate that therapies raising the levels of FGF1 and PDGFB receptors in donor cells and or corresponding ligands in an injured heart could improve the efficacy of cell-based interventions for myocardial repair.
format article
author Mark Baguma-Nibasheka
Tiam Feridooni
Feixiong Zhang
Kishore B.S. Pasumarthi
author_facet Mark Baguma-Nibasheka
Tiam Feridooni
Feixiong Zhang
Kishore B.S. Pasumarthi
author_sort Mark Baguma-Nibasheka
title Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury
title_short Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury
title_full Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury
title_fullStr Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury
title_full_unstemmed Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury
title_sort regulation of transplanted cell homing by fgf1 and pdgfb after doxorubicin myocardial injury
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/405a832b3dc947d2acd71feb9324bc7b
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AT tiamferidooni regulationoftransplantedcellhomingbyfgf1andpdgfbafterdoxorubicinmyocardialinjury
AT feixiongzhang regulationoftransplantedcellhomingbyfgf1andpdgfbafterdoxorubicinmyocardialinjury
AT kishorebspasumarthi regulationoftransplantedcellhomingbyfgf1andpdgfbafterdoxorubicinmyocardialinjury
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