Intracerebral Implantation of Autologous Peripheral Blood Stem Cells in Stroke Patients: A Randomized Phase II Study

Abstract

In our previous study, intracerebral implantation of peripheral blood stem cells (PBSCs) improved functional outcome in rats with chronic cerebral infarction. Based on this finding, a randomized, single blind controlled study was conducted in 30 patients [PBSC group (n = 15) and control group (n = 15)] with middle cerebral artery infarction confirmed on a T2-weighted MRI 6 months to 5 years after a stroke. Only subjects with neurological deficits of intermediate severity based on the National Institute of Health Stroke Scale (NIHSS; range: 9-20) that had been stable for at least 3 months were enrolled. Those in the PBSC group received subcutaneous G-CSF injections (15 μg/kg/day) for 5 consecutive days, and then stereotaxic implantation of 3-8 × 10 6 CD34 + immunosorted PBSCs. All 30 patients completed the 12-month follow-up. No serious adverse events were noted during study period. Improvements in stroke scales (NIHSS, ESS, and EMS) and functional outcomes (mRS) from baseline to the end of the 12-month follow-up period were significantly greater in the PBSC than the control group. The fiber numbers asymmetry (FNA) scores based on diffusion tensor image (DTI) tractography were reduced in every PBSC-treated subject, but not in the control group. Reduction in the FNA scores correlated well with the improvement in NIHSS. Furthermore, a positive motor-evoked potential (MEP) response by transcranial magnetic stimulation (TMS) appeared in 9 of the 15 subjects in the PBSC group. This phase II study demonstrated that implantation of autologous CD34 + PBSC was safe, feasible, and effective in improving functional outcome.

Stable Intracerebral Transplantation of Neural Stem Cells for the Treatment of Paralysis Due to Ischemic Stroke

“…Several clinical studies have been reported which evaluated transplantation of other types of cells into basal ganglia of chronic motor stroke patients with similar characteristics to our study [27][28][29][30][31]. One was bone-marrow derived cells genetically modified to transiently overexpress Notch-1 protein [27].…”

Collagen biomaterial stimulates the production of extracellular vesicles containing microRNA‐21 and enhances the proangiogenic function of CD34 + cells

“…For both circulating and resident BM hematopoietic stem/progenitor cells, CD34 positivity has been exploited to develop relatively simple methods for purification using immunomagnetic selection (12). Clinical safety and feasibility for these purified cells has been demonstrated for some medical problems, including refractory severe aplastic anemia (13), stroke (14), critical limb ischemia (15,16), nonischemic dilated cardiomyopathy (17), liver cirrhosis (18,19), and myocardial infarction (20,21). CD34 + cells are an attractive option for revascularization therapy because they are rapidly mobilized from the BM into the peripheral blood after injury (22)(23)(24) and then home to the site of tissue damage and contribute to vascular repair and angiogenesis (25)(26)(27).…”

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke

“…In Stage 3, to answer Aims 2 and 3, we have conservatively proposed a further 18 participants, which is in keeping with the numbers (range 5-18) used in previous Phase 1 clinical trials of stem cell therapy administered by intracranial injection for ischemic stroke. 18,24,33 Based on preclinical meta-analysis data with an effect size of 40% 16 at least 50 participants would be needed to investigate efficacy of stem cell therapy with 80% power at a significance level of 0.05. We propose that a firstinhuman Phase 1 clinical trial on large numbers of participants is unethical until we determine treatment safety and feasibility.…”