Research Article
In Vitro Differentiation of First Trimester Human
Umbilical Cord Perivascular Cells into Contracting
Cardiomyocyte-Like Cells
Peter Szaraz,
1,2
Matthew Librach,
1
Leila Maghen,
1
Farwah Iqbal,
1,2
Tanya A. Barretto,
1
Shlomit Kenigsberg,
1
Andrée Gauthier-Fisher,
1
and Clifford L. Librach
1,2,3,4,5
1
Create Fertility Centre, Toronto, ON, Canada M5G 1N8
2
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8
3
Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada M5G 1E2
4
Department of Physiology, University of Toronto, Toronto, ON, Canada M5S 1A8
5
Department of Obstetrics and Gynecology, Women’s College Hospital, Toronto, ON, Canada M5S 1B2
Correspondence should be addressed to Peter Szaraz; peter@createivf.com
Received 16 November 2015; Revised 30 January 2016; Accepted 11 February 2016
Academic Editor: Leonard M. Eisenberg
Copyright © 2016 Peter Szaraz et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 signifcant cardiac regeneration afer MI is yet to be
found. Te aim of our study was to investigate the cardiomyogenic diferentiation potential of frst 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 signifcantly increased
cardiomyogenic diferentiation compared to bone marrow MSCs, while their immunogenicity remained signifcantly lower as
indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based
diferentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week
of coculture, making them the frst MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior
cardiomyogenic potential coupled with benefcial immunogenic properties when compared to MSCs of older tissue sources,
suggesting that in vitro prediferentiation could be a potential strategy to increase their efectiveness in vivo.
1. Introduction
Following an acute myocardial infarction (MI), excessive
cardiomyocyte loss is associated with a cascade of events
resulting in ventricular decompensation and congestive heart
failure (CHF) [1]. Despite advances in pharmacological,
interventional, and surgical therapies, CHF contributes to
signifcant morbidity and mortality worldwide. Te heart is
a partially self-renewing organ in which stem cells play an
important restorative role: both endogenous bone marrow-
derived and heart tissue-derived stem cells participate in car-
diac regeneration following ischemic injury [2–4]. However,
in aged patients, this regenerative capacity is diminished and
generally insufcient. Te implantation of healthy donor cells
into the damaged myocardium to replace lost cardiomyocytes
and restore ventricular structure and function has been inves-
tigated since the 1990s. Various groups reported the facili-
tation of remodeling and enhancement of inherent healing
mechanisms in preclinical models of myocardial infarction
(MI) [3–6]. Te regenerative efects of the implanted cell
candidate are expected to be mediated at least in part through
the emergence of new cardiomyocytes at the injury site.
Te successful diferentiation of stem cells into car-
diomyocytes is defned via the expression of cardiac lineage
markers. Te elevation of early diferentiation markers, ofen
transcription factors (NKX2.5, Mef2C, and GATA4) [7, 8],
Hindawi Publishing Corporation
Stem Cells International
Volume 2016, Article ID 7513252, 13 pages
http://dx.doi.org/10.1155/2016/7513252