Injectable collagen scaffold with human umbilical cordderived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage:phase Ⅰ clinical trial

Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.

Elevated soluble fas blood concentrations in patients dying from spontaneous intracerebral hemorrhage

BACKGROUND Several studies of spontaneous intracerebral hemorrhage(SICH)patients have shown apoptotic changes in brain samples after hematoma evacuation.However,there have been no data on the association between blood concentrations of soluble fas(sFas)(the main surface death receptor of the extrinsic apoptosis pathway)and the prognosis of spontaneous intracranial hypotension(SIH)patients.AIM To determine whether there is an association between blood sFas concentrations and SICH patient mortality.METHODS We included patients with severe and supratentorial SIH.Severe was defined as having Glasgow Coma Scale<9.We determined serum sFas concentrations at the time of severe SICH diagnosis.RESULTS We found that non-surviving patients(n=36)compared to surviving patients(n=39)had higher ICH score(P=0.001),higher midline shift(P=0.004),higher serum sFas concentrations(P<0.001),and lower rate of early hematoma evacuation(P=0.04).Multiple logistic regression analysis showed an association between serum sFas concentrations and 30-d mortality(odds ratio=1.070;95%confidence interval=1.014-1.129;P=0.01)controlling for ICH score,midline shift,and early hematoma evacuation.CONCLUSION The association of blood sFas concentrations and SICH patient mortality is a novel finding in our study.

Establishment of a rat model of severe spontaneous intracerebral hemorrhage

Background:Severe intracerebral hemorrhage(ICH)is the most devastating subtype of stroke resulting in high mortality and disability.At present,the development of targeted treatments to minimize the high morbidity and mortality is limited partly due to the lack of a severe ICH animal model.In this study,we aimed to establish an accurate severe ICH model in rats and examine the pathological and physiological changes associated with ICH.Methods:A rat model of severe ICH model was established by intrastriatal injection of autologous blood using different blood volumes(ICH 100μL group,ICH 130μL group,ICH 160μL group,ICH 170μL group,and ICH 180μL group).The mortality was assessed during the 28-day post-ICH period.Short-and long-term neurological deficits were evaluated using the Longa method,foot fault,falling latency,and Morris water maze tests.Brain water content,hematoma volume,hemoglobin content,and magnetic resonance imaging were assessed to determine the extent of brain injury.Immunofluorescence staining was conducted to examine microglial activation and neuronal apoptosis.Hematoxylin and eosin(H&E)staining,lung water content,and western blotting were used to assess lung injury following ICH.Results:The mortality of ICH rats increased significantly with an increase in autologous blood injection.The 28-day mortality in the 100μL,130μL,160μL,170μL,and 180μL ICH groups were 5%,20%,40%,75%,and 100%,respectively.A significantly higher 28-day mortality was observed in the ICH 160μL group compared to the ICH 100μL group.The ICH 160μL group exhibited significantly increased neurological deficits,brain edema,hematoma volume,and hemoglobin content compared to the sham group.Compared with the sham operation group,the activation of microglia and neuronal death in ICH 160μL rats increased.The use of H&E staining and western blotting demonstrated that disruption of the intra-alveolar structure,alveolar edema,and infiltration of inflammatory cells and cytokines into the lung tissue were more severe in the ICH 160μL group than the sham group.Conclusions:A severe ICH model in rats was successfully established using an injection of autologous blood at a volume of 160μL.This model may provide a valuable tool to examine the pathological mechanisms and potential therapeutic interventions of severe ICH.