***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background and Purpose — Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells ( BMSCs ) in stroke . We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke . Methods — This was a phase II , multicenter , parallel group , r and omized trial with blinded outcome assessment that included 120 patients . Patients with subacute ischemic stroke were r and omly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm . Co primary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180 . Secondary outcomes were change in infa rct volume , National Institute of Health Stroke Scale ( NIHSS ) at day 90 and 180 . Main safety outcomes were adverse events , any new area of 18fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days . Results — Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset . There was no significant difference between BMSCs arm and control arm in the Barthel Index score ( 63.1 versus 63.6 ; P=0.92 ) , modified Rankin scale shift analysis ( P=0.53 ) or score > 3 ( 47.5 % versus 49.2 % ; P=0.85 ) , NIHSS score ( 6.3 versus 7.0 ; P=0.53 ) , change in infa rct volume ( −11.1 versus −7.36 ; P=0.63 ) at day 180 . Adverse events were also similar in the 2 arms , and no patient showed any new area of 18fluorodeoxyglucose uptake . Conclusions — With the methods used , results of this hitherto first r and omized controlled trial indicate that intravenous infusion of BMSCs is safe , but there is no beneficial effect of treatment on stroke outcome . Clinical Trial Registration — URLs : http://ctri.nic.in/ Clinical trials and http://www . clinical trials.gov . Unique identifiers : CTRI-ROVCTRI/2008/091/0004 and NCT0150177 BACKGROUND The influence of poststroke depression on long-term survival is poorly investigated . Thus , we aim ed to evaluate the influence of major depression disorder ( MDD ) on long-term survival in the participants from The Study of Stroke Mortality and Morbidity in Adults ( EMMA Study ) in São Paulo , Brazil . METHODS We prospect ively evaluated ischemic and hemorrhagic stroke ( HS ) cases from the EMMA Study . Baseline and stroke characteristics and cardiovascular risk factors were evaluated according to MDD assessed by the Patient Health Question naire , which was applied 30 days after index event and periodically during 1-year follow-up . We performed Kaplan-Meier survival analysis , as well as crude and multiple Cox proportional hazards models . RESULTS In this subset of the EMMA Study , we evaluated 164 ( 85.9 % ) patients with ischemic stroke and 27 ( 14.1 % ) with HS . Among these , overall incidence of MDD was 25.1 % during 1 year of follow-up , regardless stroke subtype . The peak rate of major depression postacute event was beyond 1 month . We observed a lower survival rate among individuals who developed poststroke MDD than among those who did not develop this condition after 1 year of follow-up ( 85.4 % versus 96.5 % , log rank P = .006 ) . After multiple analysis , we kept a higher risk of all-cause mortality among those who developed MDD compared to participants without MDD ( hazard ratio = 4.60 , 95 % confidence interval = 1.36 - 15.55 , P = .01 ) . CONCLUSION Our findings suggest that incident MDD is a potential marker of poor prognosis 1 year after stroke Background and Purpose — Pre clinical data suggest that cell-based therapies have the potential to improve stroke outcomes . Methods — Eighteen patients with stable , chronic stroke were enrolled in a 2-year , open-label , single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow – derived mesenchymal stem cells ( SB623 ) . Results — All patients in the safety population ( N=18 ) experienced at least 1 treatment-emergent adverse event . Six patients experienced 6 serious treatment-emergent adverse events ; 2 were probably or definitely related to surgical procedure ; none were related to cell treatment . All serious treatment-emergent adverse events resolved without sequelae . There were no dose-limiting toxicities or deaths .  Sixteen patients completed 12 months of follow-up at the time of this analysis . Significant improvement from baseline ( mean ) was reported for : ( 1 ) European Stroke Scale : mean increase 6.88 ( 95 % confidence interval , 3.5–10.3 ; P<0.001 ) , ( 2 ) National Institutes of Health Stroke Scale : mean decrease 2.00 ( 95 % confidence interval , −2.7 to −1.3 ; P<0.001 ) , ( 3 ) Fugl-Meyer total score : mean increase 19.20 ( 95 % confidence interval , 11.4–27.0 ; P<0.001 ) , and ( 4 ) Fugl-Meyer motor function total score : mean increase 11.40 ( 95 % confidence interval , 4.6–18.2 ; P<0.001 ) . No changes were observed in modified Rankin Scale . The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months ( P<0.001 for European Stroke Scale ) . Conclusions — In this interim report , SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months . Clinical Trial Registration — URL : https://www . clinical trials.gov . Unique identifier : NCT01287936 PURPOSE Bone marrow stem cells ( BMSC ) were transplanted into the perilesional area in five patients bearing sequels of stroke , to evaluate the safety of the procedure and tolerance to the transplanted cells . METHODS Cells were obtained from bone marrow sample s taken from the same patient and stereotactically implanted into the targets , determined using a combination of images , and trans-operative recording of multiunit activity . The cells were implanted in several points along tracts in the perilesional region . RESULTS No important adverse events derived from surgery or transplant were observed during the one year follow-up period , or detected using a combination of tests and functional measurements applied pre- and post-surgically . In contrast , some improvements were observed regarding the neurological condition of the patients , but the small number of patients in the study does not allow any conclusive statement . CONCLUSIONS Our results demonstrate that BMSC can be safely transplanted into the brain of patients , with excellent tolerance and without complications , using the methods described here Stem cell therapy is an emerging therapeutic modality in the treatment of stroke . We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells ( NSPCs ) and mesenchymal stromal cells ( MSCs ) in patients with ischemic stroke . Eight patients were enrolled in this study . All patients had a hemisphere with infa rct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging ( MRI ) . The patients received one of the following two types of treatment : the first treatment involved four intravenous injections of MSCs at 0.5 × 106/kg body weight ; the second treatment involved one intravenous injection of MSCs at 0.5 × 106/kg weight followed by three injections of MSCs at 5 × 106/patient and NSPCs at 6 × 106/patient through the cerebellomedullary cistern . The patients ' clinical statuses were evaluated with the National Institutes of Health Stroke Scale ( NIHSS ) , the modified Rankin Scale ( mRS ) , and the Barthel index ( BI ) . Six patients were given four cell transplantations . The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2–4 days after each therapy . One patient exhibited minor dizziness . All side effects appeared within the first 2–24 h of cell transplantation , and they resolved without special treatment . There was no evidence of neurological deterioration or neurological infection . Most importantly , no tumorigenesis was found at a 2-year follow-up . The neurological functions , disability levels , and daily living abilities of the patients in this study were improved . While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function , further studies that include larger sample s , longer follow-ups , and control groups are still needed . This manuscript is published as part of the International Association of Neurorestoratology ( IANR ) special issue of Cell Transplantation The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke . Major inclusion criteria included patients with cerebral embolism , age 20–75 years , National Institute of Health Stroke Scale ( NIHSS ) score displaying improvement of ≤5 points during the first 7 days after stroke , and NIHSS score of ≥10 on day 7 after stroke .  Bone marrow aspiration ( 25 or 50 mL ; N = 6 patients in each case ) was performed 7–10 days poststroke , and bone marrow mononuclear cells were administrated intravenously . Mean total transplanted cell numbers were 2.5 × 108 and 3.4 × 108 cells in the lower and higher dose groups , respectively . No apparent adverse effects of administering bone marrow cells were observed . Compared with the lower dose , patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes . Compared with 1 month after treatment , patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment . In comparison with historical controls , patients receiving cell therapy had significantly better neurologic outcomes . Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible . Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale r and omized controlled trials using this approach Article abstract Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke . The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits , including 12 patients ( aged 44 to 75 years ) with an infa rct 6 months to 6 years previously ( stable for at least 2 months ) . Serial evaluations ( 12 to 18 months ) showed no adverse cell-related serologic or imaging-defined effects . The total European Stroke Scale score improved in six patients ( 3 to 10 points ) , with a mean improvement 2.9 points in all patients ( p = 0.046 ) . Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site . Neuronal transplantation is feasible in patients with motor infa rct ion Transplantation of human mesenchymal stem cells has been shown to reduce infa rct size and improve functional outcome in animal models of stroke . Here , we report a study design ed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells exp and ed in autologous human serum in stroke patients . We report an unblinded study on 12 patients with ischaemic grey matter , white matter and mixed lesions , in contrast to a prior study on autologous mesenchymal stem cells exp and ed in foetal calf serum that focused on grey matter lesions . Cells cultured in human serum exp and ed more rapidly than in foetal calf serum , reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis . Autologous mesenchymal stem cells were delivered intravenously 36 - 133 days post-stroke . All patients had magnetic resonance angiography to identify vascular lesions , and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after . Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients . Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores . We did not observe any central nervous system tumours , abnormal cell growths or neurological deterioration , and there was no evidence for venous thromboembolism , systemic malignancy or systemic infection in any of the patients following stem cell infusion . The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion , compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion . Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion . Mean lesion volume as assessed by magnetic resonance imaging was reduced by > 20 % at 1 week post-cell infusion . While we would emphasize that the current study was unblinded , did not assess overall function or relative functional importance of different types of deficits , and does not exclude placebo effects or 
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While majority of the pre- clinical and clinical studies demonstrated statistically significant effects , the clinical significance of these findings was still unclear .
Addressing these issues and incorporating changes into future animal studies and human trials may lead to better success of stem cells-based therapeutics in the near future