BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.Th...BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.展开更多
Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and ...Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and safety of Wharton’s jelly-derived mesenchymal stem cell(WJ-MSC)therapy in a 4-year-old child with ASD.Using the childhood autism rating scale and Denver II develop-mental screening test,significant improvements were seen after six WJ-MSC sessions,with no adverse events over 2 years.Despite promising results,the study’s single-case design limits generalizability.Larger,multi-center trials are needed to validate the findings and assess long-term effects of WJ-MSC therapy in ASD.展开更多
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
Human umbilical mesenchymal stem cells from Wharton＇s jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted in...Human umbilical mesenchymal stem cells from Wharton＇s jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths.展开更多
Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their appli...Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.展开更多
Human Wharton＇s jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, ...Human Wharton＇s jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, a Wnt/13 catenin pathway antagonist, and LeftyA, a Nodal signaling pathway antagonist to induce differentiation into retinal progenitor cells. Inverted microscopy showed that after induction, the spindleshaped or fibroblastlike Wharton＇s jelly mesenchymal stem cells changed into bulbous cells with numerous processes. Immunofluorescent cytochemical stain ing and reversetranscription PCR showed positive expression of retinal progenitor cell markers, Pax6 and Rx, as well as weakly downregulated nestin expression. These results demonstrate that Wharton＇s jelly mesenchymal stem cells are capable of differentiating into retinal progenitor cells in vitro.展开更多
文摘BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.
文摘Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder affecting over 2%of the global population,marked by social communication deficits and repetitive behaviors.Kabatas et al explored the efficacy and safety of Wharton’s jelly-derived mesenchymal stem cell(WJ-MSC)therapy in a 4-year-old child with ASD.Using the childhood autism rating scale and Denver II develop-mental screening test,significant improvements were seen after six WJ-MSC sessions,with no adverse events over 2 years.Despite promising results,the study’s single-case design limits generalizability.Larger,multi-center trials are needed to validate the findings and assess long-term effects of WJ-MSC therapy in ASD.
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.
基金supported by the National Natural Science Foundation of China, No. 81100916, 30400464,81271316the Postdoctoral Science Foundation of China,No. 201104901907
文摘Human umbilical mesenchymal stem cells from Wharton＇s jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths.
基金supported by the National Natural Science Foundation of China,No.31171038the Natural Science Foundation of Jiangsu Province of China,No.BK2011385+3 种基金the "333" Program Funding of Jiangsu Province of China,No.BRA2016450the Training Program of Innovation and Entrepreneurship for Undergraduates of Nantong University of China,No.201510304033Z,201610304053Zthe Training Program of Innovation and Entrepreneurship for Graduates of Nantong University of China,No.YKC14050,YKC15046a grant from Funds for the Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.
基金supported by 2010 Com-advanced School Young Diaph Support Project of Heilongjiang Province,China, No. 1155G60
文摘Human Wharton＇s jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, a Wnt/13 catenin pathway antagonist, and LeftyA, a Nodal signaling pathway antagonist to induce differentiation into retinal progenitor cells. Inverted microscopy showed that after induction, the spindleshaped or fibroblastlike Wharton＇s jelly mesenchymal stem cells changed into bulbous cells with numerous processes. Immunofluorescent cytochemical stain ing and reversetranscription PCR showed positive expression of retinal progenitor cell markers, Pax6 and Rx, as well as weakly downregulated nestin expression. These results demonstrate that Wharton＇s jelly mesenchymal stem cells are capable of differentiating into retinal progenitor cells in vitro.
