ABSTRACT
Objective: The regenerative potential of bone marrow-derived mononuclear cells [MNCs] and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction [RMI] post-coronary artery bypass graft
Materials and Methods: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI [CD133, Placebo, MNCs - recent myocardial infarction] conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject [time] and group×time interaction terms
Results: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals [CI]: 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 [95% CI: -7.07 to -0.42, P=0.03]. The CD133 group showed significantly decreased non-viable segments by 75% [P=0.001] compared to the placebo and 60% [P=0.01] compared to the MNC group. We observed this improvement at both the 6- and 18-month time points
Conclusion: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types
ABSTRACT
The implantation of a CD133+ bone marrow cell population into an ischemic myocardium has emerged as a promising therapeutic modality for myocardial regeneration and restoration of ventricular contractility. While previous studies have documented the short-term safety and efficacy of CD133+ cell transplantation in patients with acute myocardial infarction, there are few reports of long-term follow-up results. Here, we present the results of long-term follow-up of our acute myocardial infarction patients who were treated with intra-myocardial injection of CD133+ cells after coronary bypass graft. After five years, 13 patients in the cell transplantation group and 5 patients in the control group underwent safety and efficacy investigations by New York Heart Association classification and two-dimensional echocardiography [2D echo]. During the five-year study period, no major cardiac adverse events were reported among patients who received CD133+ stem cells. Regarding efficiency, we observed no statistically significant treatment effects for the echocardiographic parameters [left ventricular end-diastolic and end-systolic volumes, and resting ejection fraction] measured during the follow-up period. However, detailed analysis of regional wall motion revealed an improvement in the Wall Motion Score Index from baseline to the six month follow-up, which was maintained during the follow-up period. Taken together, the long-term results of the present study indicate that transplantation of CD133+ is a safe and feasible procedure; however, we could not show any major benefits in our patients. Thus, this issue needs to be addressed by conducting other studies with more patients
Subject(s)
Humans , Transplantation, Autologous , Antigens, CD , Peptides , Glycoproteins , Myocardial Infarction , Follow-Up Studies , Coronary Artery Bypass , Echocardiography , Cohort StudiesABSTRACT
During the past decade, regenerative medicine has emerged as a key technology in the next generation of medical care, and cell therapy and organ repair using stem cells have become very attractive options for regenerative medicine. The application of stem cells in regenerative medicine has required modified methods for isolation. Furthermore, the process of cell separation plays an important role in cell therapy and regenerative medicine using stem cells. So, in this review, we compare different methods for the separation of cells from bone marrow for transplantation to humans, with emphasis on the advantages and disadvantages of each method
ABSTRACT
Background: cirrhosis, the end stage of progressive hepatic fibrosis, is characterized by distortion of the hepatic architecture and the formation of regenerative nodules. Liver transplantation is one of the few available therapies for such patients. However, due to a severe shortage of organ donors, surgical complications, transplant rejection and the high cost of this procedure much interest has focused on research to find new treatment modalities for this disease. There is accumulating evidence for the contribution of bone marrow stem cells to participate in liver regeneration
Methods: here we report on six patients with end stage liver disease who were subjected to intraportal administration of autologous bone marrow-derived CD133+ in comparison to mononuclear cells in short-term [6 months] and long-term [24 months] follow up
Results: there were no adverse effects in any of the patients during the short- and long-term follow up period. Moreover, there were no significant alterations of liver function parameters, liver enzymes, serum albumin, creatinine, serum bilirubin and/or liver volume after transplantation of both types of autologous cells in these patients
Conclusion: our study has shown both the safety and feasibility of this type of liver cell therapy and may be a bridge to liver transplantation. The trial was registered with NIH clinical trials [www.clinicaltrials.gov] as identifier: NCT00713934
ABSTRACT
Platelet transfusion is accompanied by febrile nonhemolytic transfusion reactions. The generation of cytokines [like IL-1 beta, IL-6, IL-8, and TNF-alpha] in platelet concentrates by white cells is suggested to be responsible for febrile nonhemolytic transfusion reactions. The number of white cells in the platelet concentrates is crucial to cytokine generation. This study was performed to determine whether WBC reduction in platelet concentrates by prestorage leukodepletion filters or inactivation by gamma radiation reduced the levels of these cytokines during storage for 3 days. Each of the platelet concentrates [n = 54] was prepared from a single random donor by platelet-rich plasma. This was then divided into four groups: 1] unfiltered, nonirradiated random-donner platelet concentrates [n = 13]; 2] unfiltered, gamma-irradiated random-donner platelet concentrates [n = 16]; 3] filtered, nonirradiated random- donner platelet concentrates [n = 14]; and 4] filtered, gamma-irradiated random-donner platelet concentrates [n = 11]. Cytokine levels in platelet concentrates supernatants were measured by ELISA kits according to the manufacturer's recommendations. Our results showed that IL-8 was detected in unfiltered, nonirradiated, and gamma-irradiated random-donner platelet concentrates but not in the filtered random-donner platelet concentrates. TNF-alpha was only detected in unfiltered, nonirradiated units. Compared with unfiltered platelet concentrates, prestorage filtration prevented a rise in the IL-8 and TNF-alpha on day 3 of storage. The concentration of IL-1 beta was lower than the minimum concentration value of the kit used for this purpose. IL-6 was detected only in 7 units of all filtered platelet concentrates on day 3. These data indicate that gamma irradiation can not prevent generation of IL-8 in platelet concentrates during storage, but prestorage leukoreduction of platelet concentrates can prevent accumulation of IL-6, IL-8, and TNF-alpha during storage