Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p...Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.展开更多
Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biologic...Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.展开更多
The coronavirus disease 2019(COVID-19)can be caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and has led to millions of deaths among more than 100 million infected people around the worl...The coronavirus disease 2019(COVID-19)can be caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and has led to millions of deaths among more than 100 million infected people around the world according to the declaration from World Health Organization.Dysregulated immune response of both the innate and adaptive immune systems is subsistent on COVID-19 patients,of which the degree are associated with disease severity,lung damage and long term functional disability.Current treatment options have included antiretroviral drugs,anti-inflammatory factors,antibodies,immune checkpoint inhibitors,and convalescent plasma therapy.More recently,mesenchymal stem cell(MSC)therapy has been explored for the management and control of COVID-19,particularly with the aim of preventing or at least mitigating respiratory co-morbidities.Though the safety and efficacy of stem cell therapy have been validated in multiple phase I–III clinical trials,to date,no standardized stem cell preparation,administration dosage or interval,product QA/QC testing,storage,transportation,or disposal protocols have been established.The present paper proposes a systematic methodology that addresses all the foregoing process steps and evaluation criteria for the efficacious and safe administration of MSCs in the treatment of patients infected with COVID-19.展开更多
Parkinson’s Disease(PD),second only to Alzheimer’s disease,is a neurodegenerative disease,most commonly occurring in people over the age of 65 years and is mostly caused by loss of dopamine neurons[1].Clinically,mot...Parkinson’s Disease(PD),second only to Alzheimer’s disease,is a neurodegenerative disease,most commonly occurring in people over the age of 65 years and is mostly caused by loss of dopamine neurons[1].Clinically,motor symptoms such as resting tremor,motor retardation,muscular rigidity,and disturbance of postural balance are the main symptoms,followed by non-motor symptoms such as cognitive impairment,autonomic nervous system dysfunction,depression,and sleep disorder[2].In 2016,>6.1 million people were affected with PD globally,2.4 times the number in 1990.The large number of affected people,coupled with the high mortality and disability rates,has placed a great burden on society[3].Traditional treatment methods mainly include drugs and surgery and are supplemented by physical therapy.展开更多
基金supported by the National Key Research and Development Program of China,Nos.2017YFE0122900(to BH),2019YFA0110800(to WL),2019YFA0903802(to YW),2021YFA1101604(to LW),2018YFA0108502(to LF),and 2020YFA0804003(to JW)the National Natural Science Foundation of China,Nos.31621004(to WL,BH)and 31970821(to YW)+1 种基金CAS Project for Young Scientists in Basic Research,No.YSBR-041(to YW)Joint Funds of the National Natural Science Foundation of China,No.U21A20396(to BH)。
文摘Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.
基金supported by the Natural Key Research and Development Program(No:2021YFA1101604)the key Research and Development program of Hubei province(2022BCA028)the international cooperation project of China Manned Space Program,and program for Tongji Hospital Academic Frontier Youth Team(2019A20)。
文摘Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.
基金This work was supported by The National Key R&D Program of China(Nos.2020YFC0841900,2020YFC0844000,and 2020YFC08860900)The Innovation Groups of the National Natural Science Foundation of China(No.81721002)Study on Comprehensive Treatment of Pneumonia(No.BWS20J006).
文摘The coronavirus disease 2019(COVID-19)can be caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,and has led to millions of deaths among more than 100 million infected people around the world according to the declaration from World Health Organization.Dysregulated immune response of both the innate and adaptive immune systems is subsistent on COVID-19 patients,of which the degree are associated with disease severity,lung damage and long term functional disability.Current treatment options have included antiretroviral drugs,anti-inflammatory factors,antibodies,immune checkpoint inhibitors,and convalescent plasma therapy.More recently,mesenchymal stem cell(MSC)therapy has been explored for the management and control of COVID-19,particularly with the aim of preventing or at least mitigating respiratory co-morbidities.Though the safety and efficacy of stem cell therapy have been validated in multiple phase I–III clinical trials,to date,no standardized stem cell preparation,administration dosage or interval,product QA/QC testing,storage,transportation,or disposal protocols have been established.The present paper proposes a systematic methodology that addresses all the foregoing process steps and evaluation criteria for the efficacious and safe administration of MSCs in the treatment of patients infected with COVID-19.
基金National Key R&D Program of China(2017YFA0105000)the National Natural Science Foundation of China(U1904207,81530037,91849115,and 82001973)+1 种基金the Provincial and Ministry of Health Construction Committee of Henan Province(SBGJ2020003017)the Excellent Youth Foundation of Henan Health Commission.
文摘Parkinson’s Disease(PD),second only to Alzheimer’s disease,is a neurodegenerative disease,most commonly occurring in people over the age of 65 years and is mostly caused by loss of dopamine neurons[1].Clinically,motor symptoms such as resting tremor,motor retardation,muscular rigidity,and disturbance of postural balance are the main symptoms,followed by non-motor symptoms such as cognitive impairment,autonomic nervous system dysfunction,depression,and sleep disorder[2].In 2016,>6.1 million people were affected with PD globally,2.4 times the number in 1990.The large number of affected people,coupled with the high mortality and disability rates,has placed a great burden on society[3].Traditional treatment methods mainly include drugs and surgery and are supplemented by physical therapy.
