RESUMEN
BACKGROUND AIMS: Cell therapy is promising as an exploratory cardiovascular therapy. We have recently developed an investigational new drug named Stempeucel (bone marrow-derived allogeneic mesenchymal stromal cells) for patients with acute myocardial infarction (AMI) with ST-segment elevation. A phase I/II randomized, double-blind, single-dose study was conducted to assess the safety and efficacy of intravenous administration of Stempeucel versus placebo (multiple electrolytes injection). METHODS: Twenty patients who had undergone percutaneous coronary intervention for AMI were randomly assigned (1:1) to receive intravenous Stempeucel or placebo and were followed for 2 years. RESULTS: The number of treatment-emergent adverse events observed were 18 and 21 in the Stempeucel and placebo groups, respectively. None of the adverse events were related to Stempeucel according to the investigators and independent data safety monitoring board. There was no serious adverse event in the Stempeucel group and there were three serious adverse events in the placebo group, of which one had a fatal outcome. Ejection fraction determined by use of echocardiography showed improvement in both Stempeucel (43.06% to 47.80%) and placebo (43.44% to 45.33%) groups at 6 months (P = 0.26). Perfusion scores measured by use of single-photon emission tomography and infarct volume measured by use of magnetic resonance imaging showed no significant differences between the two groups at 6 months. CONCLUSIONS: This study showed that Stempeucel was safe and well tolerated when administered intravenously in AMI patients 2 days after percutaneous coronary intervention. The optimal dose and route of administration needs further evaluation in larger clinical trials (http://clinicaltrials.gov/show/NCT00883727).
Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/terapia , Administración Intravenosa , Adulto , Anciano , Células de la Médula Ósea/citología , Método Doble Ciego , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Persona de Mediana Edad , Placebos , Adulto JovenRESUMEN
BACKGROUND: Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. METHODS: Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment - related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. RESULTS: Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. CONCLUSION: BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. TRIAL REGISTRATION: NIH website (http://www.clinicaltrials.gov/ct2/show/NCT00883870).
Asunto(s)
Trasplante de Médula Ósea/métodos , Isquemia/patología , Pierna/patología , Células Madre Mesenquimatosas/citología , Enfermedades Vasculares Periféricas/terapia , Adulto , Índice Tobillo Braquial , Células de la Médula Ósea/citología , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Fisiológica , Trasplante HomólogoRESUMEN
Human platelet lysate (HPL) was evaluated as an alternative to fetal bovine serum (FBS) in large-scale culturing of bone marrow-derived mesenchymal stromal cells (BM-MSCs) for therapeutic applications. Dulbecco's modified Eagle medium (DMEM)of low glucose (LG) and Knock Out (KO) were used with human platelet lysate (HPL) as LG-HPL and KO-HPL, and with FBS as LG-FBS and KO-FBS to culture the BM-MSCs. HPL at 10 % (v/v) supported BM-MSCs growth and subsequent isolation efficiency generated >90 × 10(6) MSCs in LG-HPL. Population doublings (PDs) and population doubling times of LG-HPL and KO-HPL (PDT) were not significantly different but LG-HPL showed a significant clonogenic potential and HPL cultures had an average PDT of 36.5 ± 6.5 h and an average PDs of 5 ± 0.7/passage. BM-MSCs cultured with LG-HPL had significantly higher immunosuppression compared to LG-FBS, but KO-HPL and KO-FBS-grown cultures were not significantly different. HPL is therefore alternative to FBS for large-scale production of BM-MSCs for therapeutic applications.