Expanded CD133⁺ Cells from Human Umbilical Cord Blood Improved Heart Function in Rats after Severe Myocardial Infarction

Abstract

Pharmacological approaches are partially effective in limiting infarct size. Cell therapies using a cell population enriched with endothelial progenitor cells (EPCs) CD133+ have opened new perspectives for the treatment of ischemic areas after infarction. This preclinical study evaluated the effect of intramyocardial transplantation of purified or expanded human umbilical cord blood-derived CD133+ cells on the recovery of rats following acute myocardial infarction (AMI). Histology studies, electrocardiogram, and fluorescence in situ hybridization (FISH) were used to evaluate heart recovery. Purified CD133+ cells, enriched in endothelial progenitor cells, when expanded in vitro acquired an endothelial-like cell phenotype expressing CD31 and von Willebrand factor (vWF). The group of infarcted rats that received expanded CD133+ cells had a more significant recovery of contraction performance and less heart remodeling than the group that received purified CD133+ cells. Either purified or expanded CD133+ cells were able to induce neovascularization in the infarcted myocardium in an equivalent manner. Few human cells were detected in the infarcted myocardium of the rats 28 days after transplantation suggesting that the effects observed might be related primarily to paracrine activity. Although both cell populations ameliorated the infarcted heart and are suitable for regeneration of the vascular system, expanded CD133+ cells are more beneficial and promising candidates for vascular regeneration.

Treatment of Chronic Kidney Disease with Extracellular Vesicles from Mesenchymal Stem Cells and CD133+ Expanded Cells: A Comparative Preclinical Analysis

“…Knowing whether one of these two sources can have better results can help when choosing the best therapy or possibly combining the two. Studies have demonstrated the potential of MSCs and eCD133 + cells in treating acute or chronic heart disease and respiratory and renal diseases [ 20 , 21 , 22 , 23 , 24 ]. Studies suggest that the therapeutic effect of these cells is mediated by modulation of the immune system, paracrine factors and the release of EVs [ 25 , 26 , 27 ].…”

Systemic Infusion of Expanded CD133+ Cells and Expanded CD133+ Cell-Derived EVs for the Treatment of Ischemic Cardiomyopathy in a Rat Model of AMI

“…Several preclinical studies that have used the injection of endothelial progenitor cells [5, 26, 27] or expanded CD133 + cells [7, 28] directly into a damaged heart have shown improved global heart function and decreased cardiac fibrosis. Khan and coworkers [29] demonstrated that mouse ESC-derived exosomes injected directly into the MI border zone have the ability to enhance neovascularization and cardiomyocyte survival and reduce fibrosis postinfarction.…”

“…In the past few years, CD133 + cells have been evaluated in clinical studies aiming to treat patients with myocardial infarction, therefore opening new avenues for the treatment of ischemic areas [5]. Within this context, our group recently reported that transplanted expanded CD133 + cells ameliorated the infarcted heart and were suitable for the regeneration of the vascular system in a preclinical study, demonstrating strong potential for vascular regeneration [7]. Despite the demonstrated capacity of CD133 + cells to integrate into ischemic tissues and contribute to healing by promoting local angiogenesis [5, 6, 8], some studies have also suggested that the beneficial effects exerted by these cells are more likely indirect and dependent on their paracrine activities, including the secretion of extracellular vesicles (EVs) [9, 10].…”

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

“…The EV components can participate not only in various physiological processes such as homeostasis, inflammation, immunological interactions, and angiogenesis, but also in pathophysiological conditions involved in the development of cancer and metastasis, autoimmune diseases, and infections of various types [ 13 , 14 , 15 , 16 , 17 , 18 ]. EVs isolated from stem and endothelial progenitors have been tested in several disease models and shown to protect and/or repair kidney, nervous and heart tissue after injury, among other tissues and organs [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. On the downside, however, EVs can also help in preparing the niche for metastases, for example [ 27 , 28 ].…”

“…Our group had previously shown that expanded CD133 + cells (E-CD133) significantly improved cardiac function in rats after severe myocardial infarction [ 21 ]. The improvement observed was mostly due to the activity of their secretome, which seems to be related to the induction of angiogenesis [ 21 ].…”