Cord Blood Cell Therapy Alters LV Remodeling and Cytokine Expression but does not Improve Heart Function after Myocardial Infarction in Rats

Abstract

Objective: In this study the ability of unrestricted somatic stem cells (USSC) and mononuclear cord blood cells (MN-CBC) was tested to improve heart function and left ventricular (LV) remodeling after myocardial infarction (MI). Methods: The cells were delivered by i.v. or intramyocardial injections in rat models of MI by permanent coronary artery occlusion and by ischemia/reperfusion (I/R) injury. Heart function and remodeling was followed by recurrent echocardiography over 8 or 12 weeks after which catheterization was performed. Results: Although injected labeled cells could be observed within the myocardium for up to 6 d, there was no sign of cardiac regeneration 8 or 12 weeks after MI. However, the mRNA expression of components of the extracellular matrix was attenuated in the infarct scar 12 weeks after MI and cell injection. Additionally, the expression of interleukin (IL)-6 but not of IL-1β increased at the site of injury and the adjacent border-zone 12 weeks after I/R and USSC-injection. However, these effects did not translate into improved heart function or attenuated LV dilatation. Conclusion: These data indicate that cord blood cell implantation after MI acts through paracrine mechanisms to modify remodeling rather than myocyte regeneration. The role of myofibroblasts and the optimal conditions of cell application need to be determined to translate these mechanisms into functional improvement.

Human Unrestricted Somatic Stem Cell Administration Fails to Protect Nude Mice from Cisplatin-Induced Acute Kidney Injury

“…Unexpectedly, the current study showed that at least in this animal model, USSC not only did not protect against kidney failure, but also significantly worsened it. This finding is similar to two previous studies that have shown USSC transplantation in rat and swine animal models of myocardial ischemia does not improve heart function [32,33]. In contrast to our data, Morigi et al [34] have recently shown that intravenous infusion of human umbilical cord blood MSC in immunodeficient mice with cisplatin-induced kidney injury is protective in terms of survival, renal function and histopathologic measures.…”

Improvement in Cardiac Function following Transplantation of Human Umbilical Cord Matrix-Derived Mesenchymal Cells

“…Studies have indicated the feasibility of MSCs derived from extraembryonic tissues [11], including UCB cells for the repair of ischemic heart diseases [12,13,14]. However, there are conflicting data in the literature regarding the use of UCB cells for the repair of ischemic myocardium in different animal models [15,16]. Several studies have evaluated the effects of UCBs on MI animal models.…”

Integration of functional bacterial artificial chromosomes into human cord blood-derived multipotent stem cells

“…USSC have been shown to enable reconstitution of femoral defects in mice 3,5,52 and to improve heart function after myocardial infarctions. 3,7,53,54 In this study, mesodermal differentiation capacity of the clones was confirmed by the ability of the cells to mineralize after culturing in medium that induces stem cells down the osteogenic differentiation pathway. Distinct clusters of Alizarin Red S-stained cells were observed in both clones confirming successful mineralization.…”