Heart failure, as we all know, is one of the major reasons of mortality and morbidity world-wide. Recent findings have stated that heart valve can undergo regeneration, which ideally can eliminate the usage of bovine and porcine valve replacements. This involves the usage of an effective allogeneic product, in conjunction with an effective delivery system. It was during the year 2007 that ERC, the endometrial regenerating cell, mesencymal type stem cells was discovered. It was immediately concluded that ERCs are far superior than most of the bone marrow stem cells, which is the most commonly deployed source in cell development. ERC is superior in expandability, is involved in the production of a wide range of growth factors and is highly angiogenic in nature. This is conjunction with an ideal delivery system can aid in the rapid regeneration of heart valve cells.
Therapeutic efficiency of the ERCs
The higher degree of angiogenesis that happens in the endometrium led to a high speculation that ERCs play a major role in the physiology of the process. This, supplemented with a high rate of angiogenic factors such as the MMPs, Estradiol and the VEGF aided in the process of the cycle. Further, it was noticed that ovariectomy diminished the production of angiogenesis and VEGF. To further determine the efficacy of the ERCs and to estimate their role in angiogenesis, a murine hind limb ischemia model was created and a group of animals were treated with human ERC, whereas the controls weren't. Results were surprising when levels of anti-inflammatory cytokines where stimulation and inflammatory cytokines were diminished.
The delivery technique
Conventionally, all cell-delivery types, especially the cardiac cells involved intramyocardial, transendocardial or transepicardial, or antegrade mode of delivery into the coronary artery. A few of these routes have the disadvantage of surgical invasion, complex mapping by means of NOGA device, and more. Further, the intramyocardial means of delivery is not ideal for patients with a thin myocardium as it could lead to perforation. Comparatively, retrograde therapy has been used effectively for the delivery of protein and protein-based therapeutics and less in cardiac cell delivery. A porcine study employed the usage of retrograde mode of administration of FGF-2 protein, to prevent the induction of stenosis. Radio-labeled FGF2 showed that twice the level of FGF 2 was absorbed when compared to antegrade mode of infusion. Further, there were significant increases transmural flow of blood and myocardial function.
Another study also suggested the usage of retrograde method to distribute progenitor cells in a rat infarction model. After 28 days, there were significant improvements in cardiac function, decreased fibrosis and increased cell retention.
Retrograde administration coupled with ERC therapy
Several studies have assessed the effectiveness of retrograde mode of administration. For instance, a study involved the retrograde administration of beta-galactase and luciferase in porcine coronary artery. Slight increased levels of gene expression was observed when compared to antegrade method and similar results were also obtained in the interstitial expression of the eGFP in porcine heart that were induced by means of retrograde method along with naked DNA. In another method, B-gal that encodes a plasmid results in higher levels of gene expression when introduced by the retrograde method.
Effective trials were launched in 2012 to examine the efficacy and safety of ERCs in patients suffering from Congestive Heart Failure. Retrograde mode of delivery through the coronary sinuses, by means of minimal invasion, is supportive of efficiency and nearly 60 patients are being studied upon. Congestive Heart Failure was confirmed by means of various cardiac function tests, physician assessments, and patient assessment tests. It also includes symptomatic heart failure and other modes of cardiac interventions. Efficacy end points are obtained after the following time periods; cardiac function is assessed at the end of 3 months, 6 months, and 1 year.
However, despite an effective model, it is important to note that cardiac cell therapy requires highly efficient and scalable methods. ERC is a superior donor when compared to many other types of stem cells and possess exquisite angiogenic properties when compared to many other types of clinical stem cells. The success of the trial entirely depends on results that re further obtained and in the establishment of a regenerative cell therapy that is purely of the cardiovascular type. Indeed, stem-cell based therapies are enticing.
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