Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarctionCitation formats

  • External authors:
  • Verena Schwach
  • Maria Gomes Fernandes
  • Saskia Maas
  • Sophie Gerhardt
  • Roula Tsonaka
  • Louise van der Weerd
  • Robert Passier
  • Christine L Mummery
  • Daniela C F Salvatori

Standard

Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction. / Schwach, Verena; Fernandes, Maria Gomes; Maas, Saskia; Gerhardt, Sophie; Tsonaka, Roula; van der Weerd, Louise; Passier, Robert; Mummery, Christine L; Birket, Matthew J; Salvatori, Daniela C F.

In: Cardiovascular research, 2019.

Research output: Contribution to journalArticlepeer-review

Harvard

Schwach, V, Fernandes, MG, Maas, S, Gerhardt, S, Tsonaka, R, van der Weerd, L, Passier, R, Mummery, CL, Birket, MJ & Salvatori, DCF 2019, 'Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction', Cardiovascular research. https://doi.org/10.1093/cvr/cvz181

APA

Schwach, V., Fernandes, M. G., Maas, S., Gerhardt, S., Tsonaka, R., van der Weerd, L., Passier, R., Mummery, C. L., Birket, M. J., & Salvatori, D. C. F. (2019). Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction. Cardiovascular research. https://doi.org/10.1093/cvr/cvz181

Vancouver

Schwach V, Fernandes MG, Maas S, Gerhardt S, Tsonaka R, van der Weerd L et al. Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction. Cardiovascular research. 2019. https://doi.org/10.1093/cvr/cvz181

Author

Schwach, Verena ; Fernandes, Maria Gomes ; Maas, Saskia ; Gerhardt, Sophie ; Tsonaka, Roula ; van der Weerd, Louise ; Passier, Robert ; Mummery, Christine L ; Birket, Matthew J ; Salvatori, Daniela C F. / Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction. In: Cardiovascular research. 2019.

Bibtex

@article{87e323ff74754f25968d63a581760625,
title = "Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction",
abstract = "AIMS: Cardiovascular diseases caused by loss of functional cardiomyocytes are a major cause of mortality and morbidity worldwide due in part to the low regenerative capacity of the adult human heart. Human pluripotent stem cell (hPSC)-derived cardiovascular progenitor cells (CPCs) are a potential cell source for cardiac repair. The aim of this study was to examine the impact of extensive remuscularization and coincident revascularization on cardiac remodeling and function in a mouse model of myocardial infarction (MI) by transplanting doxycycline (DOX)-inducible (Tet-On-MYC) hPSC-derived CPCs in vivo and inducing proliferation and cardiovascular differentiation in a drug-regulated manner.METHODS AND RESULTS: CPCs were injected firstly at a non-cardiac site in Matrigel suspension under the skin of immunocompromised mice to assess their commitment to the cardiovascular lineage and ability to self-renew or differentiate in vivo when instructed by systemically delivered factors including DOX and basic fibroblast growth factor (bFGF). CPCs in Matrigel were then injected intramyocardially in mice subjected to MI to assess whether expandable CPCs could mediate cardiac repair. Transplanted CPCs expanded robustly both subcutis and in the myocardium using the same DOX/growth factor inducing regime. Upon withdrawal of these cell-renewal factors, CPCs differentiated with high efficiency at both sites into the major cardiac lineages including cardiomyocytes, endothelial cells and smooth muscle cells. After MI, engraftment of CPCs in the heart significantly reduced fibrosis in the infarcted area and prevented left ventricular remodeling, although cardiac function determined by MRI was unaltered.CONCLUSIONS: Replacement of large areas of muscle may be required to regenerate the heart of patients following MI. Our human/mouse model demonstrated that proliferating hPSC-CPCs could reduce infract size and fibrosis resulting in formation of large grafts. Importantly, the results suggested that expanding transplanted cells in situ at the progenitor stage maybe be an effective alternative causing less tissue damage than injection of very large numbers of cardiomyocytes.",
author = "Verena Schwach and Fernandes, {Maria Gomes} and Saskia Maas and Sophie Gerhardt and Roula Tsonaka and {van der Weerd}, Louise and Robert Passier and Mummery, {Christine L} and Birket, {Matthew J} and Salvatori, {Daniela C F}",
note = "{\textcopyright} The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.",
year = "2019",
doi = "10.1093/cvr/cvz181",
language = "English",
journal = "Cardiovascular research",
issn = "0008-6363",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction

AU - Schwach, Verena

AU - Fernandes, Maria Gomes

AU - Maas, Saskia

AU - Gerhardt, Sophie

AU - Tsonaka, Roula

AU - van der Weerd, Louise

AU - Passier, Robert

AU - Mummery, Christine L

AU - Birket, Matthew J

AU - Salvatori, Daniela C F

N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2019

Y1 - 2019

N2 - AIMS: Cardiovascular diseases caused by loss of functional cardiomyocytes are a major cause of mortality and morbidity worldwide due in part to the low regenerative capacity of the adult human heart. Human pluripotent stem cell (hPSC)-derived cardiovascular progenitor cells (CPCs) are a potential cell source for cardiac repair. The aim of this study was to examine the impact of extensive remuscularization and coincident revascularization on cardiac remodeling and function in a mouse model of myocardial infarction (MI) by transplanting doxycycline (DOX)-inducible (Tet-On-MYC) hPSC-derived CPCs in vivo and inducing proliferation and cardiovascular differentiation in a drug-regulated manner.METHODS AND RESULTS: CPCs were injected firstly at a non-cardiac site in Matrigel suspension under the skin of immunocompromised mice to assess their commitment to the cardiovascular lineage and ability to self-renew or differentiate in vivo when instructed by systemically delivered factors including DOX and basic fibroblast growth factor (bFGF). CPCs in Matrigel were then injected intramyocardially in mice subjected to MI to assess whether expandable CPCs could mediate cardiac repair. Transplanted CPCs expanded robustly both subcutis and in the myocardium using the same DOX/growth factor inducing regime. Upon withdrawal of these cell-renewal factors, CPCs differentiated with high efficiency at both sites into the major cardiac lineages including cardiomyocytes, endothelial cells and smooth muscle cells. After MI, engraftment of CPCs in the heart significantly reduced fibrosis in the infarcted area and prevented left ventricular remodeling, although cardiac function determined by MRI was unaltered.CONCLUSIONS: Replacement of large areas of muscle may be required to regenerate the heart of patients following MI. Our human/mouse model demonstrated that proliferating hPSC-CPCs could reduce infract size and fibrosis resulting in formation of large grafts. Importantly, the results suggested that expanding transplanted cells in situ at the progenitor stage maybe be an effective alternative causing less tissue damage than injection of very large numbers of cardiomyocytes.

AB - AIMS: Cardiovascular diseases caused by loss of functional cardiomyocytes are a major cause of mortality and morbidity worldwide due in part to the low regenerative capacity of the adult human heart. Human pluripotent stem cell (hPSC)-derived cardiovascular progenitor cells (CPCs) are a potential cell source for cardiac repair. The aim of this study was to examine the impact of extensive remuscularization and coincident revascularization on cardiac remodeling and function in a mouse model of myocardial infarction (MI) by transplanting doxycycline (DOX)-inducible (Tet-On-MYC) hPSC-derived CPCs in vivo and inducing proliferation and cardiovascular differentiation in a drug-regulated manner.METHODS AND RESULTS: CPCs were injected firstly at a non-cardiac site in Matrigel suspension under the skin of immunocompromised mice to assess their commitment to the cardiovascular lineage and ability to self-renew or differentiate in vivo when instructed by systemically delivered factors including DOX and basic fibroblast growth factor (bFGF). CPCs in Matrigel were then injected intramyocardially in mice subjected to MI to assess whether expandable CPCs could mediate cardiac repair. Transplanted CPCs expanded robustly both subcutis and in the myocardium using the same DOX/growth factor inducing regime. Upon withdrawal of these cell-renewal factors, CPCs differentiated with high efficiency at both sites into the major cardiac lineages including cardiomyocytes, endothelial cells and smooth muscle cells. After MI, engraftment of CPCs in the heart significantly reduced fibrosis in the infarcted area and prevented left ventricular remodeling, although cardiac function determined by MRI was unaltered.CONCLUSIONS: Replacement of large areas of muscle may be required to regenerate the heart of patients following MI. Our human/mouse model demonstrated that proliferating hPSC-CPCs could reduce infract size and fibrosis resulting in formation of large grafts. Importantly, the results suggested that expanding transplanted cells in situ at the progenitor stage maybe be an effective alternative causing less tissue damage than injection of very large numbers of cardiomyocytes.

U2 - 10.1093/cvr/cvz181

DO - 10.1093/cvr/cvz181

M3 - Article

C2 - 31287499

JO - Cardiovascular research

JF - Cardiovascular research

SN - 0008-6363

ER -