Human Umbilical Cord‐Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia
Stem Cells Translational Medicine
CHUAN -BIN LIU ,a,* HE HUANG ,b,* PING SUN ,c SHI -ZE MA ,c AN -HENG LIU ,a JIAN XUE ,a JIN -HUI FU ,a YU -QIAN LIANG ,c BING LIU ,d DONG -YING WU ,c SHUANG -HONG L¨U ,a XIAO -ZHONG ZHANGa
Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord‐derived mesenchymal stromal cells (UC‐MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC‐MSCs originated from Wharton’s jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC‐MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC‐MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC‐MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p < .05). The systolic thickening fraction in the infarcted left ventricular wall was also improved (41.2% ± 3.3% vs. 46.2% ± 2.3%, p < .01). Additionally, the administration of UC‐MSCs promoted collateral development and myocardial perfusion. The indices of fibrosis and apoptosis were also significantly reduced. Immunofluorescence staining showed clusters of CM‐DiI‐labeled cells in the border zone, some of which expressed von Willebrand factor. These results suggest that UC‐MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia.
This is the first study to provide evidence that intracoronary delivery combined with multiple intravenous infusions of UC‐MSCs improves LV function, perfusion, and remodeling in a large animal model of chronic myocardial ischemia. In the present study, we observed neither tumor nor teratoma formation in human UC‐MSC‐transplanted animals, and no sustained ventricular arrhythmia or anaphylaxis was observed. Because these cells can be isolated from medical waste, expanded, banked, and administered to patients at any time without immunological rejection, human UC‐MSCs might be an ideal cell source for cardiac cell therapy and hold promise as an off‐the‐shelf product.