Direct intracardiac injection of umbilical cord-derived stromal cells and umbilical cord blood-derived endothelial cells for the treatment of ischemic cardiomyopathy

Abstract

The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of cardiovascular disease, which produces high rates of morbidity and mortality. A therapeutic option that has emerged in the last decade is cell therapy. The aim of this study was to compare the effect of transplanting human umbilical cord-derived stromal cells (UCSCs), human umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat model. IC was induced by left coronary artery ligation, and baseline echocardiography was performed seven days later. Animals with a left ventricular ejection fraction (LVEF) of 40% were selected for the study. On the ninth day after IC was induced, the animals were randomized into the following experimental groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after treatment, an echocardiographic analysis was performed, followed by euthanasia. The animals in all of the cell therapy groups, regardless of the cell type transplanted, had less collagen deposition in their heart tissue and demonstrated a significant improvement in myocardial function after IC. Furthermore, there was a trend of increasing numbers of blood vessels in the infarcted area. The median value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for cellular cardiomyoplasty and can be an effective therapy for improving cardiac function following IC.

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

“…The correlation coefficients between the volume of blood collected versus the number of mononuclear cells, the number of mononuclear cells versus the number of CD133 + cells, and the number of CD133 + cells versus the number of expanded CD133 + cells were 0.69, 0.84, and 0.32, respectively. As it has been previously shown by our group [ 14 , 19 ] that the phenotype of the enriched CD133 + cell population, as determined by surface markers, changes considerably after expansion, acquiring an endothelial-like phenotype. After isolation, the average percentages of cells were as follows: 81% CD133, 82% CD34, 12% CD45, 5% CD14, 8% CD105, 1% CD31, and 6% vWF.…”

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

“…The advantages and limitations of each stem cell with regard to the possible emergence of ethical concerns (symbolized by ¥), the invasiveness and collection (from + to ++++), the isolation procedure, the abundance (from + to ++++), expansion and proliferation rate, the transdifferentiation capacity, the paracrine effects or/and cardiomyogenic potential, the survival and engraftment capacity as well as the immunogenic, oncogenic or teratogenic risks is given in the accessory side tables. The left table abridges bone marrow-derived stem cells [3,[19][20][21]27,28], cortical bone-derived stem cells [32,33], adipose tissue-derived stem cells [34,37,39,41] and gestation-related stem cells [42][43][44][45][46][47][48][49]51,54] and the right table abridges cardiac stem cells [57,59,60], skeletal muscle stem cells [62,63,66] and induced pluripotent stem cells [67,[69][70][71]. The human body scheme was constructed with images sourced from Servier Medical Art (http://www.servier.com/ Powerpoint-image-bank) and Cientic website (http://www.cientic.com/).…”

“…Pregnancy byproducts represent an important source of stem cells which can be obtained from a plethora of sources, such as placenta [42][43][44], chorionic plate [45], amniotic fluid [46], umbilical cord [47,48] and its blood [48][49][50][51]. These immune-privileged materials offer several advantages (Fig.…”

“…This would be particularly important for elder patients, whose stem cell quality is expected to reduce with age [12]. Similarly to the above stem cell groups, it is thought that these cells act mainly through paracrine activity, stimulating vascularization, cardiomyogenesis, and inhibiting inflammation, fibrosis and apoptosis [42][43][44][45]47,48,51]. Also related to gestation, MSCs obtained from fetal heart tissue (fC-MSC) and embryonic stem cells (ESC) have been proposed as alternative multipotent cells with the ability to differentiate into CMs, endothelial and smooth muscle cells.…”

“…For example, association of umbilical cord-derived MSCs and umbilical cord-derived endothelial cells was already tested in a rat model of AMI. Though, dual therapy did not show extra benefit over single therapies [48]. Recently, in an attempt to surmount the benefits of dual therapies, cardiac chimeras were developed, by fusion of CSC and BMMSC.…”