In Vitro Differentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte-Like Cells.
Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting that in vitro predifferentiation could be a potential strategy to increase their effectiveness in vivo.
Create Fertility Centre, Toronto, ON, Canada M5G 1N8; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8.
Peter
P
Szaraz
Create Fertility Centre, Toronto, ON, Canada M5G 1N8.
Matthew
M
Librach
Create Fertility Centre, Toronto, ON, Canada M5G 1N8.
Leila
L
Maghen
Create Fertility Centre, Toronto, ON, Canada M5G 1N8; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8.
Farwah
F
Iqbal
Create Fertility Centre, Toronto, ON, Canada M5G 1N8.
Tanya A
TA
Barretto
Create Fertility Centre, Toronto, ON, Canada M5G 1N8.
Shlomit
S
Kenigsberg
Create Fertility Centre, Toronto, ON, Canada M5G 1N8.
Andrée
A
Gauthier-Fisher
Create Fertility Centre, Toronto, ON, Canada M5G 1N8; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8; Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada M5G 1E2; Department of Physiology, University of Toronto, Toronto, ON, Canada M5S 1A8; Department of Obstetrics and Gynecology, Women's College Hospital, Toronto, ON, Canada M5S 1B2.
Clifford L
CL
Librach