| [Research background]Cerebrovascular disease (CVD) is a very serious problem about health and society, because of high morbidity rate, high disability rate, high mortality rate, high recurrence rate and high medical cost ratio. It causes a heavy burden to the family and society. Cerebral infarction is the most common type in CVD with the proportion about70%. To date, only recombinant tissue-type plasminogen activator (rt-PA) obtains Food and Drug Administration’s permission to cure acute cerebral infarction. However, only a minority of patients can obtain this treatment because of the strict treatment time window. With the advancement of cell engineering, stem cell transplantation opens a novel door for the treatment of cerebral ischemia. Among them, endothelial progenitor cells (EPCs) are a high concern in adult stem cells. In the stimulation of physiological or pathological factors, EPCs can mobilize, proliferate and differentiate from bone marrow to target site to participate in repair of the damaged vessels and provide a microenvironment with rich blood vessels for neurogenesis. At present, there are a lot of animal experiments about EPCs transplantation in cerebral infarction in the world, which confirms that EPCs transplantation is safe and effective. It is a pity that there is no report up to now about clinical research of EPCs transplantation in stroke patients both at home and abroad. Doctor Chen Zhenzhou implanted3×107and3×106separately to rabbits and rats of experimental animal models of middle cerebral artery occlusion, which appeared no adverse reaction and good for repairmen of vessels and nerves. On this basis, we will conduct clinical trial of phase I for the first time about autologous endothelial progenitor cells transplantation in patients with ischemia stroke.[Objective]To observe the safety of autologous endothelial progenitor cells transplantation in patients with ischemia stroke.[Methods]Collect volunteers in accord with inclusion and exclusion criteria. The suitable patients signed informed consent and were allocated to transplantation group or control group out of their desire. All the patients participating in this clinical trial accepted normative therapeutic schedule and neurological rehabilitation of cerebral infarction. In the same time, record the following information (such as demographic data, illness and diagnosis, allergy history, past medical history and risk factors, laboratory test and auxiliary examination) to fully grasp the clinical data of patients so that we could analysis the safety of cell transplantation.Bone marrow cells were aspirated under posterior superior iliac spine in patients of transplantation group. Bone marrow mononuclear cells were isolated by density gradient centrifugation. Mononuclear cells were placed in a culture flask with fibronection (Fn), and were cultivated in nutrient solution of "EC basal medium-2 (EBM-2)+EGM-2MV SingleQuots", measured the cell surface markers using flow cytometry instrument before infusion. Before transplantation, all EPCs should be strictly controlled to ensure the quality of transplanted cells. EPCs proliferated to enough quantify were transplanted from peripheral vein, suspending in5%normal saline100ml with autoserum. EPCs-treated patients received2.5×106/kilogram of body weight twice, with the second transplantation after3days (a total of5×106/kilogram of body weight).Nerve function evaluation was performed serially in the fourth/eighth/twelfth month after transplantation for the patients in transplantation group and control group. All the patients should regularly accept laboratory test and auxiliary examination. Record the treatment information, adverse reactions, complications and so on.[Results]There were2patients in transplantation group and4patients in control group. All the information about participants was reported in the case report form (CRF).Successfully isolate, cultivate, proliferate and identify EPCs. Transglant EPCs to patients from peripheral vein, when the EPCs were enough.Compared with control group, no adverse reaction and complications relating cells transplantation happened to EPCs-treated patients in the following-up one year. And no history of hospitalization was found in transplantation group. Nerve function and ability of daily living activities gradually improved in transplantation group. Because it was a lack of EPCs-treated patients, statistical analysis were not performed. Patient I returned to society and patients II returned to community in the end. Compared with control group, the prognosis of EPCs-treated patients was better. Because of lack in the number of study objects, statistical analysis cloud not be performed. [Conclusion]In patients with cerebral infarction, the intravenous infusion of autologous EPCs appears to be safe which were extracted, cultivated and proliferated in vitro. |
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