ABSTRACT
Objective: Amyotrophic lateral sclerosis [ALS] is the most severe disorder within the spectrum of motor neuron diseases [MND] that has no effective treatment and a progressively fatal outcome. We have conducted two clinical trials to assess the safety and feasibility of intravenous [IV] and intrathecal [IT] injections of bone marrow derived mesenchymal stromal cells [BM-MSCs] in patients with ALS
Materials and Methods: This is an interventional/experimental study. We enrolled 14 patients that met the following inclusion criteria: definitive diagnosis of sporadic ALS, ALS Functional Rating Scale [ALS-FRS] .24, and .40% predicted forced vital capacity [FVC]. All patients underwent bone marrow [BM] aspiration to obtain an adequate sample for cell isolation and culture. Patients in group 1 [n=6] received an IV and patients in group 2 [n=8] received an IT injection of the cell suspension. All patients in both groups were followed at 24 hours and 2, 4, 6, and 12 months after the injection with ALS-FRS, FVC, laboratory tests, check list of side effects and brain/spinal cord magnetic resonance imaging [MRI]. In each group, one patient was lost to follow up one month after cell injection and one patient from IV group died due to severe respiratory insufficiency and infection
Results: During the follow up there were no reports of adverse events in terms of clinical and laboratory assessments. In MRI, there was not any new abnormal finding. The ALS-FRS score and FVC percentage significantly reduced in all patients from both groups
Conclusion: This study has shown that IV and IT transplantation of BM-derived stromal cells is safe and feasible [Registration numbers: NCT01759797 and NCT01771640]
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
Objective: Nonunion is defined as a minimum of a 9-month period of time since an injury with no visibly progressive signs of healing for 3 months. Recent studies show that application of mesenchymal stromal cells [MSCs] in the laboratory setting is effective for bone regeneration. Animal studies have shown that MSCs can be used to treat nonunions. For the first time in an Iranian population, the present study investigated the safety of MSC implantation to treat human lower limb long bone nonunion
Materials and Methods: It is a prospective clinical trial for evaluating the safety of using autologus bone marrow derived mesenchymal stromal cells for treating nonunion. Orthopedic surgeons evaluated 12 patients with lower limb long bone nonunion for participation in this study. From these, 5 complied with the eligibility criteria and received MSCs. Under fluoroscopic guidance, patients received a one-time implantation of 20-50x106 MSCs into the nonunion site. All patients were followed by anterior-posterior and lateral X-rays from the affected limb, in addition to hematological, biochemical, and serological laboratory tests obtained before and 1, 3, 6, and 12 months after the implantation. Possible adverse effects that included local or systemic, serious or non-serious, and related or unrelated effects were recorded during this time period
Results: From a safety perspective, all patients tolerated the MSCs implantation during the 12 months of the trial. Three patients had evidence of bony union based on the after implantation X- rays
Conclusion: The results have suggested that implantation of bone marrow-derived MSCs is a safe treatment for nonunion. A double-blind, controlled clinical trial is required to assess the efficacy of this treatment
Subject(s)
Adult , Adolescent , Female , Humans , Male , Middle Aged , Young Adult , Autografts , Transplantation, Autologous/methods , Plastic Surgery Procedures , Mesenchymal Stem Cells , Lower Extremity , Prospective StudiesABSTRACT
Objective: nonunion is defined as a minimum of 9 months since injury without any visible progressive signs of healing for 3 months. Recent literature has shown that the application of mesenchymal stromal cells is safe, in vitro and in vivo, for treating long bone nonunion. The present study was performed to investigate the safety of mesenchymal stromal cell [MSC] implantation in combination with platelet lysate [PL] product for treating human long bone nonunion
Materials and Methods: in this case series clinical trial, orthopedic surgeons visited eighteen patients with long bone nonunion, of whom 7 complied with the eligibility criteria. These patients received mesenchymal stromal cells [20 million cells implanted once into the nonunion site using a fluoroscopic guide] in combination with PL product. For evaluation of the effects of this intervention all the patients were followed up by taking anterior-posterior and lateral X-rays of the affected limb before and 1, 3, 6, and 12 months after the implantation. All side effects [local or systemic, serious or non-serious, related or unrelated] were observed during this time period
Results: from a safety perspective the MSC implantation in combination with PL was very well tolerated during the 12 months of the trial. Four patients were healed; based on the control X- ray evidence, bony union had occurred
Conclusion: results from the present study suggest that the implantation of bone marrow-derived MSCs in combination with PL is safe for the treatment of nonunion. A double blind, controlled clinical trial is required to assess the efficacy of this treatment [Registration Number: NCT01206179]
ABSTRACT
During the resent years there has been interest in using bone marrow stem cells to treat liver cirrhosis. However, there is a potential concern for malignant transformation after stem cell therapy. The aim of this study was to evaluate the development of hepatocellular carcinoma [HCC] after autologous bone marrow stem cell transplantation for liver cirrhosis. All the patients who underwent autologous stem cell transplantation for liver cirrhosis between 2005 and 2011 at our center were enrolled. Cellular infusion was made through peripheral vein, portal vein, or hepatic artery.The patients were invited to undergo screening for hepatocellular carcinoma. The screening was made with ultrasonography and alpha-feto protein [AFP] measurement. Thirty two patients [18 males] were included in the study. Mean age of patients was 45.7 years. Fifteen patients [47%] received mesenchymal stem cell [MSC], 9 [28%] received bone marrow mononuclear cells, 5 [16%] were given CD 133-positive bone marrow cells, and 3 [9%] patients received CD 34-positive bone marrow cells. Mean duration of follow up was 20.5months. Mean serum level of AFP was 2.8 ng/ml at baseline and 3.4ng/ml at the end of follow up [p= 0.3]. One patient was found to have hepatocellular carcinoma three months after infusion of bone marrow mononuclear cells. The incidence rate for HCC was 1.8 cases per 100 person-years in this study. Autologous bone marrow stem cell infusion does not appear to increase the risk of hepatocellular carcinoma. The incidence rate of HCC in this study is comparable or even less than the reported rates of HCC in cohort studies of cirrhotic patients
ABSTRACT
Some investigation has indicated that adipose-derived stem cells possess different surface epitopes and differentiation potential according to the localization of fat pad from which the cells were derived. In the present study proliferation capacity and aging of such cells were explored. Adherent cells were isolated from the collagenase digests of adipose tissues excised from rat epicardial and epididymal regions and propagated with several subcultures. The cells were then investigated whether or not they were able to differentiate into bone, cartilage and adipose cell lineages. Studied cells from two adipose tissues were also compared with respect to their in vitro proliferation capacity. The presence of senescent cells in the culture was determined and compared using senescence-associated [SA] beta-galactosidase staining method. Successful differentiations of the cells were indicative of their mesenchymal stem cells [MSCs] identity. Epicardial adipose-derived cells tended to have a short population doubling time [45 +/- 9.6 hr] than the epididymal adipose-derived stem cells [69 +/- 16 hr, P< 0.05]. Colonogenic activity and the growth curve characteristics were all better in the culture of stem cells derived from epicardial compared to epididymal adipose tissue. Comparatively more percentage of senescent cells was present at the cultures derived from epididymal adipose tissue [P< 0.05]. Our data emphasize on the differences existed between the stem cells derived from adipose depots of different anatomical sites in terms of their proliferative capacity and in vitro aging. Such data can help understand varying results reported by different laboratories involved in adipose stem cell investigations