Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4

Abstract

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.

Targeting the Endothelium to Achieve Cardioprotection

“…Consequently, their reparative capacity after infarction is reduced. Treatment of EPC with different molecules such as thymosin beta-4 ( Poh et al, 2020 ) and the overexpression of Sonic hedgehog (Q. Xiao et al, 2019 ) recover the reparative properties of EPC after MI in the context of diabetes by inducing their mobilization (restoring their circulating levels) or promoting angiogenesis.…”

Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells

“…Currently, there is little information on the role of Tb4 on diabetic ECs. Previously, we showed that Tb4 improved migration of CD34 + /KDR + circulating endothelial progenitor cells (EPCs) from diabetic fatty rats [ 23 , 24 ]. Furthermore, in the current study, we aimed to use diabetic-hiPSC-ECs as diabetic EC models to study the role of Tb4 on proliferation, viability, senescence, and angiogenesis of diabetic ECs.…”

Cells in Cardiovascular Disease: Using Diversity to Confront Adversity

“…The mingling of pathological mechanisms affecting cardiovascular health is clearly reflected by the risk of CVD associated with metabolic diseases, including conditions such as obesity or diabetes. This connection is explored in several studies of the present volume [ 5 , 15 ]. A link of these factors is studied by Actis-Dato et al in their study of the involvement of LRP-1 in insulin response in a myoblast cell line [ 23 ].…”

“…Endothelial cells not only are players in CVD, but are also a therapeutic option [ 14 ]. Poh et al [ 15 ] explore the effects of thymosin-β4 (Tβ4) on endothelial progenitor cells (EPCs) in vitro, and in vivo in a diabetic rat model subjected myocardial infarction (MI). In the same field, Kutikhin et al [ 16 ] provide an interesting characterization of endothelial colony-forming cells and its similarity with mature endothelial cells, a topic that has attracted a lot of attention recently, with the publication of several detailed maps of endothelial cell populations that underscore both the versatility of these cellular type and its implications on disease [ 17 ].…”

“…We wanted to examine the cellular mechanisms that lie behind the processes of repair and recovery of functionality after tissue damage in the context of CVD. Interestingly, most of the contributions proposed a target or mechanism that could be explored for therapy [2,[5][6][7]9,12,15,25]. We have to be personally satisfied with the outcome, and we hope that you will find it also useful for your research.…”