BACKGROUND Traumatic spinal cord injury(SCI)is a life-altering condition that results in long-term complications,including progressive neurodegeneration and cord atrophy.It presents a significant unmet medical need wi...BACKGROUND Traumatic spinal cord injury(SCI)is a life-altering condition that results in long-term complications,including progressive neurodegeneration and cord atrophy.It presents a significant unmet medical need with extensive social and economic burdens.AIM To evaluate the safety and preliminary efficacy of allogeneic mesenchymal stem cells derived from Wharton’s jelly(WJ-MSCs)in patients with chronic complete SCI.The primary objective was to assess whether WJ-MSCs could facilitate neurological recovery and improve the quality of life in this patient population.METHODS This open-label,multicenter phase I study investigated the effects of administering WJ-MSCs via three delivery routes:Intrathecal(for localized spinal targeting);intramuscular(for targeting end organ);and intravenous(for systemic immunomodulation).While all three routes were used concurrently to enhance therapeutic synergy,neurological,sensory,and functional scales were used to assess overall efficacy.Participants with chronic SCI(duration of at least 6 months)who had significant impairment and disability were eligible for inclusion.WJ-MSCs were administered twice monthly for 2 months,with each route receiving a dose of 1×10^(6)cells/kg.Patients were closely monitored for 1 year following treatment.RESULTS At baseline,participants displayed considerable functional deficits,as indicated by the following scores:Functional independence measure of 77.5±2.26;Modified Ashworth Scale of 15.83±4.83;American Spinal Injury Association(ASIA)Motor score of 1.67±2.66;ASIA Light Touch and Pin-Prick scores of 62±18.42 each;Wexner Incontinence Score of 20;and Qualiveen Short Form,a validated questionnaire specifically designed to assess the impact of urinary dysfunction on quality of life in individuals with SCI,score of 32.Following WJ-MSC therapy,significant improvements were observed in all neurological functions over the 1-year follow-up.Notably,the ASIA Motor score improved significantly(χ^(2)=23.938,P<0.001),and Qualiveen Short Form scores demonstrated a substantial enhancement in quality of life(z=-2.214,P<0.05).CONCLUSION This phase I study,conducted without a control group,suggests that the administration of WJ-MSCs through multiple routes is both safe and potentially effective in patients with chronic complete SCI.However,the observed neurological improvements cannot be solely attributed to WJ-MSC therapy,as concurrent pharmacological and rehabilitative interventions were not controlled.These findings indicated that WJ-MSC therapy may offer a promising approach for enhancing neurological function and quality of life in this challenging patient population.Further research with larger cohorts and extended follow-up is necessary to validate these preliminary results.展开更多
BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is one of the leading causes of death and long-term neurological impairment in the pediatric population.Despite a limited number of treatments to cure HIE,stem cell thera...BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is one of the leading causes of death and long-term neurological impairment in the pediatric population.Despite a limited number of treatments to cure HIE,stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE.AIM To investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE.METHODS The study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE.Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)were intrathecally(IT),intramuscularly(IM),and intravenously administered to participants at a dose of 1×10^(6)/kg for each administration route twice monthly for 2 mo.In different follow-up durations,the effect of WJ-MSCs administration on HIE,the quality of life,prognosis of patients,and side effects were investigated,and patients were evaluated for neurological,cognitive functions,and spasticity using the Wee Functional Independence Measure(Wee FIM)Scale and Modified Ashworth(MA)Scale.RESULTS For all participants(n=6),the mean duration of exposure to hypoxia was 39.17+18.82 min,the mean time interval after HIE was 21.83±26.60 mo,the mean baseline Wee FIM scale score was 13.5±0.55,and the mean baseline MA scale score was 35±9.08.Three patients developed only early complications such as low-grade fever,mild headache associated with IT injection,and muscle pain associated with IM injection,all of which were transient and disappeared within 24 h.The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations,electroencephalographies,laboratory tests,and neurological and functional scores of patients.Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up.The mean Wee FIM scale score of participants increased from 13.5±0.55 to 15.17±1.6 points(mean±SD)at 1 mo(z=-1.826,P=0.068)and to 23.5±3.39 points at 12 mo(z=-2.207,P=0.027)post-treatment.The percentage of patients who achieved an excellent functional improvement(Wee FIM scale total score=126)increased from 10.71%(at baseline)to 12.03%at 1 mo and to 18.65%at 12 mo posttreatment.CONCLUSION Both the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements.The results of this study support conducting further randomized,placebo-controlled studies on this treatment in the pediatric population.展开更多
BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is a leading cause of morbidity and mortality in the adult as well as in the neonate,with limited options for treatment and significant dysfunctionality.AIM To investigat...BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is a leading cause of morbidity and mortality in the adult as well as in the neonate,with limited options for treatment and significant dysfunctionality.AIM To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells(MSCs)in HIE patients.METHODS Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included.All patients were given Wharton’s jelly-derived MSCs at 1×106/kg intrathecally,intravenously,and intramuscularly twice a month for two months.The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups.Functional independence measure(FIM),modified Ashworth,and Karnofsky scales were used to assess any side effects,neurological and cognitive functions,and overall outcomes.RESULTS The 8 subjects included in the study had a mean age of 33.25±10.18 years.Mean HIE exposure and mean post-HIE durations were 45.63±10.18 and 19.67±29.04 mo,respectively.Mean FIM score was 18.38±1.06,mean modified Ashworth score was 43.5±4.63,and mean Karnofsky score was 20.For the first 24 h,5 of the patients experienced a subfebrile state,accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration.Neurological and functional examinations,laboratory tests,electroencephalography,and magnetic resonance imaging were performed to assess safety of treatment.Mean FIM score increased by 20.88±3.31 in the first month(P=0.027)and by 31.38±14.69 in 12 mo(P=0.012).The rate of patients with an FIM score of 126 increased from 14.58%to 16.57%in the first month and 24.90%in 12 mo.CONCLUSION Multiple triple-route Wharton’s jelly-derived MSC administrations were found to be safe for HIE patients,indicating neurological and functional improvement.Based on the findings obtained here,further randomized and placebo research could be performed.展开更多
文摘BACKGROUND Traumatic spinal cord injury(SCI)is a life-altering condition that results in long-term complications,including progressive neurodegeneration and cord atrophy.It presents a significant unmet medical need with extensive social and economic burdens.AIM To evaluate the safety and preliminary efficacy of allogeneic mesenchymal stem cells derived from Wharton’s jelly(WJ-MSCs)in patients with chronic complete SCI.The primary objective was to assess whether WJ-MSCs could facilitate neurological recovery and improve the quality of life in this patient population.METHODS This open-label,multicenter phase I study investigated the effects of administering WJ-MSCs via three delivery routes:Intrathecal(for localized spinal targeting);intramuscular(for targeting end organ);and intravenous(for systemic immunomodulation).While all three routes were used concurrently to enhance therapeutic synergy,neurological,sensory,and functional scales were used to assess overall efficacy.Participants with chronic SCI(duration of at least 6 months)who had significant impairment and disability were eligible for inclusion.WJ-MSCs were administered twice monthly for 2 months,with each route receiving a dose of 1×10^(6)cells/kg.Patients were closely monitored for 1 year following treatment.RESULTS At baseline,participants displayed considerable functional deficits,as indicated by the following scores:Functional independence measure of 77.5±2.26;Modified Ashworth Scale of 15.83±4.83;American Spinal Injury Association(ASIA)Motor score of 1.67±2.66;ASIA Light Touch and Pin-Prick scores of 62±18.42 each;Wexner Incontinence Score of 20;and Qualiveen Short Form,a validated questionnaire specifically designed to assess the impact of urinary dysfunction on quality of life in individuals with SCI,score of 32.Following WJ-MSC therapy,significant improvements were observed in all neurological functions over the 1-year follow-up.Notably,the ASIA Motor score improved significantly(χ^(2)=23.938,P<0.001),and Qualiveen Short Form scores demonstrated a substantial enhancement in quality of life(z=-2.214,P<0.05).CONCLUSION This phase I study,conducted without a control group,suggests that the administration of WJ-MSCs through multiple routes is both safe and potentially effective in patients with chronic complete SCI.However,the observed neurological improvements cannot be solely attributed to WJ-MSC therapy,as concurrent pharmacological and rehabilitative interventions were not controlled.These findings indicated that WJ-MSC therapy may offer a promising approach for enhancing neurological function and quality of life in this challenging patient population.Further research with larger cohorts and extended follow-up is necessary to validate these preliminary results.
文摘BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is one of the leading causes of death and long-term neurological impairment in the pediatric population.Despite a limited number of treatments to cure HIE,stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE.AIM To investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE.METHODS The study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE.Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)were intrathecally(IT),intramuscularly(IM),and intravenously administered to participants at a dose of 1×10^(6)/kg for each administration route twice monthly for 2 mo.In different follow-up durations,the effect of WJ-MSCs administration on HIE,the quality of life,prognosis of patients,and side effects were investigated,and patients were evaluated for neurological,cognitive functions,and spasticity using the Wee Functional Independence Measure(Wee FIM)Scale and Modified Ashworth(MA)Scale.RESULTS For all participants(n=6),the mean duration of exposure to hypoxia was 39.17+18.82 min,the mean time interval after HIE was 21.83±26.60 mo,the mean baseline Wee FIM scale score was 13.5±0.55,and the mean baseline MA scale score was 35±9.08.Three patients developed only early complications such as low-grade fever,mild headache associated with IT injection,and muscle pain associated with IM injection,all of which were transient and disappeared within 24 h.The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations,electroencephalographies,laboratory tests,and neurological and functional scores of patients.Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up.The mean Wee FIM scale score of participants increased from 13.5±0.55 to 15.17±1.6 points(mean±SD)at 1 mo(z=-1.826,P=0.068)and to 23.5±3.39 points at 12 mo(z=-2.207,P=0.027)post-treatment.The percentage of patients who achieved an excellent functional improvement(Wee FIM scale total score=126)increased from 10.71%(at baseline)to 12.03%at 1 mo and to 18.65%at 12 mo posttreatment.CONCLUSION Both the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements.The results of this study support conducting further randomized,placebo-controlled studies on this treatment in the pediatric population.
文摘BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is a leading cause of morbidity and mortality in the adult as well as in the neonate,with limited options for treatment and significant dysfunctionality.AIM To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells(MSCs)in HIE patients.METHODS Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included.All patients were given Wharton’s jelly-derived MSCs at 1×106/kg intrathecally,intravenously,and intramuscularly twice a month for two months.The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups.Functional independence measure(FIM),modified Ashworth,and Karnofsky scales were used to assess any side effects,neurological and cognitive functions,and overall outcomes.RESULTS The 8 subjects included in the study had a mean age of 33.25±10.18 years.Mean HIE exposure and mean post-HIE durations were 45.63±10.18 and 19.67±29.04 mo,respectively.Mean FIM score was 18.38±1.06,mean modified Ashworth score was 43.5±4.63,and mean Karnofsky score was 20.For the first 24 h,5 of the patients experienced a subfebrile state,accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration.Neurological and functional examinations,laboratory tests,electroencephalography,and magnetic resonance imaging were performed to assess safety of treatment.Mean FIM score increased by 20.88±3.31 in the first month(P=0.027)and by 31.38±14.69 in 12 mo(P=0.012).The rate of patients with an FIM score of 126 increased from 14.58%to 16.57%in the first month and 24.90%in 12 mo.CONCLUSION Multiple triple-route Wharton’s jelly-derived MSC administrations were found to be safe for HIE patients,indicating neurological and functional improvement.Based on the findings obtained here,further randomized and placebo research could be performed.
