Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the mul...Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.展开更多
In this editorial,we comment on the article by Jiang et al.Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by the accumulation of fat in the liver without evidence of significant alcoh...In this editorial,we comment on the article by Jiang et al.Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by the accumulation of fat in the liver without evidence of significant alcohol consumption.NAFLD can progress to more serious conditions such as non-alcoholic steatohepatitis,fibrosis,cirrhosis and hepatocellular carcinoma.This disease is considered an emerging public health problem in several countries as it has increased in recent decades,currently affecting around 30%of the world’s population.The fatty diet and the current lifestyle of the Western population are identified as the main culprits of the disease.Drug treatment aims to reduce the weight of patients and treat metabolic alterations and diseases,including type 2 diabetes mellitus and other comorbidities that coexist with NAFLD.In this scenario,cell therapy with mesenchymal stem/stromal cells(MSCs)has been proposed as a perspective treatment of numerous diseases that do not have definitive curative treatment,such as Crohn’s disease and coronavirus disease 2019.This is due to the versatile,immunomodulatory and regenerative properties of MSCs.The possibility of MSCs being used in patients with severe liver disease progressing to non-alcoholic steatohepatitis or cirrhosis is summarized,because of the therapeutic benefits in reducing fibrosis of affected livers.It remains to be seen when MSC transplantation should be indicated for NAFLD,that is,at what stage of the disease and which phenotype,as well as deciding on the best source of MSCs,the dose,and the administration route.We conclude that well-designed clinical trials are essential in order to obtain robust results for the implementation of this modality in the medical practice.展开更多
BACKGROUND Knee osteoarthritis(OA)is a degenerative joint disease traditionally viewed through the lens of cartilage degradation.However,emerging evidence positions subchondral bone pathology-particularly bone marrow ...BACKGROUND Knee osteoarthritis(OA)is a degenerative joint disease traditionally viewed through the lens of cartilage degradation.However,emerging evidence positions subchondral bone pathology-particularly bone marrow lesions(BMLs)-as a key contributor to pain,progression,and structural deterioration.Mesenchymal stem cell exhaustion within the osteoarthritic subchondral zone further impairs intrinsic repair mechanisms,reinforcing the rationale for biologic interventions.AIM To evaluate the clinical efficacy of bone marrow aspirate concentrate(BMAC)therapy for knee OA,comparing subchondral vs intra-articular delivery routes,and elucidating the therapeutic impact on symptom relief and structural preservation.METHODS Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,five clinical studies were included-comprising three randomized controlled trials and two prospective cohorts-with pooled data from 298 knees.Data on functional outcomes,imaging findings,and progression to total knee arthroplasty(TKA)were extracted and qualitatively synthesized.RESULTS Subchondral BMAC injections demonstrated superior improvements compared to intra-articular injection or placebo:Knee Injury and Osteoarthritis Outcome Score improved from 49.1±1.9 to 61.2±6.3 at 12 months(P<0.05),Knee Society Score increased from 57±12 to 87.3±12 at two years,and Western Ontario and McMaster Universities Arthritis Index scores showed significant improvement favoring combined approaches.Magnetic resonance imaging analyses revealed mean BML volume regression of 2.1 cm3,with 80%of knees avoiding TKA over 13-year follow-up.Magnetic resonance imaging analyses revealed regression of BMLs and increased cartilage preservation in subchondral-treated knees.Long-term data indicated delayed progression to TKA and biomechanical improvements(e.g.,Hip-Knee-Ankle angle correction).No major adverse events were reported.CONCLUSION Targeting subchondral bone with BMAC addresses underlying OA pathology and may offer disease-modifying potential beyond symptom relief.These findings support a paradigm shift toward whole-joint biologic therapy,positioning the subchondral matrix as a therapeutic epicenter in OA management.展开更多
The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens milli...The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health.Two current studies have indicated a favorable role for mesenchymal stem/stromal cells(MSCs)in clinical remission of COVID-19 associated pulmonary diseases,yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction.In the present review,we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury,acute respiratory distress syndrome,and pulmonary fibrosis.Furthermore,we review the underlying mechanism of MSCs including direct-and trans-differentiation,autocrine and paracrine anti-inflammatory effects,homing,and neovascularization,as well as constitutive microenvironment.Finally,we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice.Collectively,this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.展开更多
Dental pulp stem/stromal cells(DPSCs)are fibroblast-like,neural crest-derived,and multipotent cells that can differentiate into several lineages.They are relatively easy to isolate from healthy and inflamed pulps,with...Dental pulp stem/stromal cells(DPSCs)are fibroblast-like,neural crest-derived,and multipotent cells that can differentiate into several lineages.They are relatively easy to isolate from healthy and inflamed pulps,with little ethical concerns and can be successfully cryopreserved and thawed.The therapeutic effects of DPSCs derived from animal or human sources have been extensively studied through in-vitro and in-vivo animal experiments and the findings indicated that DPSCs are effective not only for dental diseases but also for systemic diseases.Understanding that translational research is a critical step through which the fundamental scientific discoveries could be translated into applicable diagnostics and therapeutics that directly benefit humans,several clinical studies were carried out to generate evidence for the efficacy and safety of autogenous or allogeneic human DPSCs(hDPSCs)as a treatment modality for use in cell-based therapy,regenerative medicine/dentistry and tissue engineering.In clinical medicine,hDPSCs were effective for treating acute ischemic stroke and human exfoliated deciduous teeth-conditioned medium(SHED-CM)repaired vascular damage of the corpus cavernous,which is the main cause of erectile dysfunction.Whereas in clinical dentistry,autologous SHED was able to rege-nerate necrotic dental pulp after implantation into injured teeth,and micrografts enriched with autologous hDPSCs and collagen sponge were considered a treatment option for human intrabony defects.In contrast,hDPSCs did not add a significant regenerative effect when they were used for the treatment of post-extraction sockets.Large-scale clinical studies across diverse populations are still lacking to provide robust evidence on the safety and efficacy of hDPSCs as a new treatment option for various human diseases including dental-related problems.展开更多
Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality rate.In this sense,the bone marrow(BM)mesenchymal stem/stromal cel...Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality rate.In this sense,the bone marrow(BM)mesenchymal stem/stromal cells(MSCs)are critical for BM/bone homeostasis,and failures in their functionality,transform the BM into a premetastatic niche(PMN).We previously found that BM-MSCs from advanced breast cancer patients(BCPs,infiltrative ductal carcinoma,stage III-B)have an abnormal profile.This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients.A comparative analysis was undertaken,which included self-renewal capacity,morphology,proliferation capacity,cell cycle,reactive oxygen species(ROS)levels,and senescence-associatedβ‑galactosidase(SA‑β‑gal)staining of BMderived MSCs isolated from 14 BCPs and 9 healthy volunteers(HVs).Additionally,the expression and activity of the telomerase subunit TERT,as well as telomere length,were measured.Expression levels of pluripotency,osteogenic,and osteoclastogenic genes(OCT-4,SOX-2,M-CAM,RUNX-2,BMP-2,CCL-2,M-CSF,and IL-6)were also determined.The results showed that MSCs from BCPs had reduced,self-renewal and proliferation capacity.These cells also exhibited inhibited cell cycle progression and phenotypic changes,such as an enlarged and flattened appearance.Additionally,there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length.We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression.We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.展开更多
Advances in regenerative medicine correlate strongly with progress in the use of adipose tissue-derived mesenchymal stem/stromal cells.The range of therapeutic indications has also expanded over recent years.Numerous ...Advances in regenerative medicine correlate strongly with progress in the use of adipose tissue-derived mesenchymal stem/stromal cells.The range of therapeutic indications has also expanded over recent years.Numerous recent studies have highlighted the primary importance of paracrine secretion by these cells.Though it is interesting to compare the different types of such secretions,we believe that exosomes(extra-cellular vesicles possessing the same properties as their source cells)will likely be the main key in tomorrow’s cell therapy.Exosomes also have many advantages compared to the direct use of cells,making these particles amajor target in fundamental and translational research.展开更多
Allogeneic hematopoietic stem cell transplantation is a deterministic curative procedure for various hematologic disorders and congenital immunodeficiency.Despite its increased use,the mortality rate for patients unde...Allogeneic hematopoietic stem cell transplantation is a deterministic curative procedure for various hematologic disorders and congenital immunodeficiency.Despite its increased use,the mortality rate for patients undergoing this procedure remains high,mainly due to the perceived risk of exacerbating graft-versushost disease(GVHD).However,even with immunosuppressive agents,some patients still develop GVHD.Advanced mesenchymal stem/stromal cell(MSC)strategies have been proposed to achieve better therapeutic outcomes,given their immunosuppressive potential.However,the efficacy and trial designs have varied among the studies,and some research findings appear contradictory due to the challenges in characterizing the in vivo effects of MSCs.This review aims to provide real insights into this clinical entity,emphasizing diagnostic,and therapeutic considerations and generating pathophysiology hypotheses to identify research avenues.The indications and timing for the clinical application of MSCs are still subject to debate.展开更多
Mesenchymal stem/stromal cells(MSCs)are extensively studied as cell-therapy agents for neurological diseases.Recent studies consider exosomes secreted by MSCs as important mediators for MSCs’neuroprotective functions...Mesenchymal stem/stromal cells(MSCs)are extensively studied as cell-therapy agents for neurological diseases.Recent studies consider exosomes secreted by MSCs as important mediators for MSCs’neuroprotective functions.Exosomes transfer functional molecules including proteins,lipids,metabolites,DNAs,and coding and non-coding RNAs from MSCs to their target cells.Emerging evidence shows that exosomal microRNAs(miRNAs)play a key role in the neuroprotective properties of these exosomes by targeting several genes and regulating various biological processes.Multiple exosomal miRNAs have been identified to have neuroprotective effects by promoting neurogenesis,neurite remodeling and survival,and neuroplasticity.Thus,exosomal miRNAs have significant therapeutic potential for neurological disorders such as stroke,traumatic brain injury,and neuroinflammatory or neurodegenerative diseases and disorders.This review discusses the neuroprotective effects of selected miRNAs(miR-21,miR-17-92,miR-133,miR-138,miR-124,miR-30,miR146a,and miR-29b)and explores their mechanisms of action and applications for the treatment of various neurological disease and disorders.It also provides an overview of state-of-the-art bioengineering approaches for isolating exosomes,optimizing their yield and manipulating the miRNA content of their cargo to improve their therapeutic potential.展开更多
Mesenchymal stromal/stem cells(MSCs)are currently applied in regenerative medicine and tissue engineering.Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefi...Mesenchymal stromal/stem cells(MSCs)are currently applied in regenerative medicine and tissue engineering.Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefits for patients.MSCs derived from either human adult or perinatal tissues have their own unique advantages in their medical practices.Usually,clinical studies are conducted by using of cultured MSCs after thawing or short-term cryopreserved-then-thawed MSCs prior to administration for the treatment of a wide range of diseases and medical disorders.Currently,cryogenically banking perinatal MSCs for potential personalized medicine for later use in lifetime has raised growing interest in China as well as in many other countries.Meanwhile,this has led to questions regarding the availability,stability,consistency,multipotency,and therapeutic efficiency of the potential perinatal MSC-derived therapeutic products after longterm cryostorage.This opinion review does not minimize any therapeutic benefit of perinatal MSCs in many diseases after short-term cryopreservation.This article mainly describes what is known about banking perinatal MSCs in China and,importantly,it is to recognize the limitation and uncertainty of the perinatal MSCs stored in cryobanks for stem cell medical treatments in whole life.This article also provides several recommendations for banking of perinatal MSCs for potentially future personalized medicine,albeit it is impossible to anticipate whether the donor will benefit from banked MSCs during her/his lifetime.展开更多
Mesenchymal stem/stromal cells(MSCs)have various properties that make them promising candidates for stem cell-based therapies in clinical settings.These include self-renewal,multilineage differentiation,and immunoregu...Mesenchymal stem/stromal cells(MSCs)have various properties that make them promising candidates for stem cell-based therapies in clinical settings.These include self-renewal,multilineage differentiation,and immunoregulation.However,recent studies have confirmed that aging is a vital factor that limits their function and therapeutic properties as standardized clinical products.Understanding the features of senescence and exploration of cell rejuvenation methods are necessary to develop effective strategies that can overcome the shortage and instability of MSCs.This review will summarize the current knowledge on characteristics and functional changes of aged MSCs.Additionally,it will highlight cell rejuvenation strategies such as molecular regulation,noncoding RNA modifications,and microenvironment controls that may enhance the therapeutic potential of MSCs in clinical settings.展开更多
Osteoporosis is a systemic bone disease,which leads to decreased bone mass and an increased risk of fragility fractures.Currently,there are many anti-resorption drugs and osteosynthesis drugs,which are effective in th...Osteoporosis is a systemic bone disease,which leads to decreased bone mass and an increased risk of fragility fractures.Currently,there are many anti-resorption drugs and osteosynthesis drugs,which are effective in the treatment of osteoporosis,but their usage is limited due to their contraindications and side effects.In regenerative medicine,the unique repair ability of mesenchymal stem cells(MSCs)has been favored by researchers.The exosomes secreted by MSCs have signal transduction and molecular delivery mechanisms,which may have therapeutic effects.In this review,we describe the regulatory effects of MSCs-derived exosomes on osteoclasts,osteoblasts,and bone immunity.We aim to summarize the preclinical studies of exosome therapy in osteoporosis.Furth-ermore,we speculate that exosome therapy can be a future direction to improve bone health.展开更多
Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used...Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used MSCs toalleviate COVID-19-associated acute lung injury and cytokine storm, reportedpromising results. However, the evidence came from a case report, case series,and clinical trials with a limited number of participants. Therefore, more studiesare needed to get robust proof of MSC beneficial effects.展开更多
Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies,and pretreatment has proven to enhance cell vitality and function.In a recent publication,Li et al explored a new combination o...Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies,and pretreatment has proven to enhance cell vitality and function.In a recent publication,Li et al explored a new combination of pretreatment condi-tions.Here,we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.展开更多
Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the...Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.展开更多
基金Supported by Taishan Scholar Special Funding,No.tsqnz20240858Medical and Health Technology Project of Shandong Province,No.202402050122+4 种基金Science and Technology Development Plan of Jinan Municipal Health Commission,No.2024301008Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau,No.202430055Natural Science Foundation of Jiangxi Province,No.20224BAB206077Gansu Provincial Hospital Intra-Hospital Research Fund Project,No.22GSSYB-6and the 2022 Master/Doctor/Postdoctoral Program of National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor,No.NHCDP2022004 and No.NHCDP2022008.
文摘Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.
文摘In this editorial,we comment on the article by Jiang et al.Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by the accumulation of fat in the liver without evidence of significant alcohol consumption.NAFLD can progress to more serious conditions such as non-alcoholic steatohepatitis,fibrosis,cirrhosis and hepatocellular carcinoma.This disease is considered an emerging public health problem in several countries as it has increased in recent decades,currently affecting around 30%of the world’s population.The fatty diet and the current lifestyle of the Western population are identified as the main culprits of the disease.Drug treatment aims to reduce the weight of patients and treat metabolic alterations and diseases,including type 2 diabetes mellitus and other comorbidities that coexist with NAFLD.In this scenario,cell therapy with mesenchymal stem/stromal cells(MSCs)has been proposed as a perspective treatment of numerous diseases that do not have definitive curative treatment,such as Crohn’s disease and coronavirus disease 2019.This is due to the versatile,immunomodulatory and regenerative properties of MSCs.The possibility of MSCs being used in patients with severe liver disease progressing to non-alcoholic steatohepatitis or cirrhosis is summarized,because of the therapeutic benefits in reducing fibrosis of affected livers.It remains to be seen when MSC transplantation should be indicated for NAFLD,that is,at what stage of the disease and which phenotype,as well as deciding on the best source of MSCs,the dose,and the administration route.We conclude that well-designed clinical trials are essential in order to obtain robust results for the implementation of this modality in the medical practice.
文摘BACKGROUND Knee osteoarthritis(OA)is a degenerative joint disease traditionally viewed through the lens of cartilage degradation.However,emerging evidence positions subchondral bone pathology-particularly bone marrow lesions(BMLs)-as a key contributor to pain,progression,and structural deterioration.Mesenchymal stem cell exhaustion within the osteoarthritic subchondral zone further impairs intrinsic repair mechanisms,reinforcing the rationale for biologic interventions.AIM To evaluate the clinical efficacy of bone marrow aspirate concentrate(BMAC)therapy for knee OA,comparing subchondral vs intra-articular delivery routes,and elucidating the therapeutic impact on symptom relief and structural preservation.METHODS Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,five clinical studies were included-comprising three randomized controlled trials and two prospective cohorts-with pooled data from 298 knees.Data on functional outcomes,imaging findings,and progression to total knee arthroplasty(TKA)were extracted and qualitatively synthesized.RESULTS Subchondral BMAC injections demonstrated superior improvements compared to intra-articular injection or placebo:Knee Injury and Osteoarthritis Outcome Score improved from 49.1±1.9 to 61.2±6.3 at 12 months(P<0.05),Knee Society Score increased from 57±12 to 87.3±12 at two years,and Western Ontario and McMaster Universities Arthritis Index scores showed significant improvement favoring combined approaches.Magnetic resonance imaging analyses revealed mean BML volume regression of 2.1 cm3,with 80%of knees avoiding TKA over 13-year follow-up.Magnetic resonance imaging analyses revealed regression of BMLs and increased cartilage preservation in subchondral-treated knees.Long-term data indicated delayed progression to TKA and biomechanical improvements(e.g.,Hip-Knee-Ankle angle correction).No major adverse events were reported.CONCLUSION Targeting subchondral bone with BMAC addresses underlying OA pathology and may offer disease-modifying potential beyond symptom relief.These findings support a paradigm shift toward whole-joint biologic therapy,positioning the subchondral matrix as a therapeutic epicenter in OA management.
基金Supported by Shandong Provincial Natural Science Foundation,No.ZR2020QC097China Postdoctoral Science Foundation,No.2019M661033+7 种基金Jiangxi Key New Product Incubation Program Funded by Technical Innovation Guidance Program of Shangrao city,No.2020G002Tianjin Science and Technology Project for Overseas Students,No.JH-20180070802Natural Science Foundation of Tianjin,No.19JCQNJC12500Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences,No.2018PT31048Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences,No.2019PT310013National Science and Technology Major Projects of China for“Major New Drugs Innovation and Development”,No.2014ZX09508002-003National Natural Science Foundation of China,No.81330015and Science and Technology Project of Tianjin,No.17ZXSCSY00030.
文摘The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health.Two current studies have indicated a favorable role for mesenchymal stem/stromal cells(MSCs)in clinical remission of COVID-19 associated pulmonary diseases,yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction.In the present review,we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury,acute respiratory distress syndrome,and pulmonary fibrosis.Furthermore,we review the underlying mechanism of MSCs including direct-and trans-differentiation,autocrine and paracrine anti-inflammatory effects,homing,and neovascularization,as well as constitutive microenvironment.Finally,we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice.Collectively,this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.
文摘Dental pulp stem/stromal cells(DPSCs)are fibroblast-like,neural crest-derived,and multipotent cells that can differentiate into several lineages.They are relatively easy to isolate from healthy and inflamed pulps,with little ethical concerns and can be successfully cryopreserved and thawed.The therapeutic effects of DPSCs derived from animal or human sources have been extensively studied through in-vitro and in-vivo animal experiments and the findings indicated that DPSCs are effective not only for dental diseases but also for systemic diseases.Understanding that translational research is a critical step through which the fundamental scientific discoveries could be translated into applicable diagnostics and therapeutics that directly benefit humans,several clinical studies were carried out to generate evidence for the efficacy and safety of autogenous or allogeneic human DPSCs(hDPSCs)as a treatment modality for use in cell-based therapy,regenerative medicine/dentistry and tissue engineering.In clinical medicine,hDPSCs were effective for treating acute ischemic stroke and human exfoliated deciduous teeth-conditioned medium(SHED-CM)repaired vascular damage of the corpus cavernous,which is the main cause of erectile dysfunction.Whereas in clinical dentistry,autologous SHED was able to rege-nerate necrotic dental pulp after implantation into injured teeth,and micrografts enriched with autologous hDPSCs and collagen sponge were considered a treatment option for human intrabony defects.In contrast,hDPSCs did not add a significant regenerative effect when they were used for the treatment of post-extraction sockets.Large-scale clinical studies across diverse populations are still lacking to provide robust evidence on the safety and efficacy of hDPSCs as a new treatment option for various human diseases including dental-related problems.
基金Supported by the FONCYT,Argentina(PICT 2016-#1093)CONICET,Argentina(PIP2014-2016,#300)Fundación Florencio Fiorini(Subsidio 2021-2022),Argentina.
文摘Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality rate.In this sense,the bone marrow(BM)mesenchymal stem/stromal cells(MSCs)are critical for BM/bone homeostasis,and failures in their functionality,transform the BM into a premetastatic niche(PMN).We previously found that BM-MSCs from advanced breast cancer patients(BCPs,infiltrative ductal carcinoma,stage III-B)have an abnormal profile.This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients.A comparative analysis was undertaken,which included self-renewal capacity,morphology,proliferation capacity,cell cycle,reactive oxygen species(ROS)levels,and senescence-associatedβ‑galactosidase(SA‑β‑gal)staining of BMderived MSCs isolated from 14 BCPs and 9 healthy volunteers(HVs).Additionally,the expression and activity of the telomerase subunit TERT,as well as telomere length,were measured.Expression levels of pluripotency,osteogenic,and osteoclastogenic genes(OCT-4,SOX-2,M-CAM,RUNX-2,BMP-2,CCL-2,M-CSF,and IL-6)were also determined.The results showed that MSCs from BCPs had reduced,self-renewal and proliferation capacity.These cells also exhibited inhibited cell cycle progression and phenotypic changes,such as an enlarged and flattened appearance.Additionally,there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length.We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression.We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.
文摘Advances in regenerative medicine correlate strongly with progress in the use of adipose tissue-derived mesenchymal stem/stromal cells.The range of therapeutic indications has also expanded over recent years.Numerous recent studies have highlighted the primary importance of paracrine secretion by these cells.Though it is interesting to compare the different types of such secretions,we believe that exosomes(extra-cellular vesicles possessing the same properties as their source cells)will likely be the main key in tomorrow’s cell therapy.Exosomes also have many advantages compared to the direct use of cells,making these particles amajor target in fundamental and translational research.
文摘Allogeneic hematopoietic stem cell transplantation is a deterministic curative procedure for various hematologic disorders and congenital immunodeficiency.Despite its increased use,the mortality rate for patients undergoing this procedure remains high,mainly due to the perceived risk of exacerbating graft-versushost disease(GVHD).However,even with immunosuppressive agents,some patients still develop GVHD.Advanced mesenchymal stem/stromal cell(MSC)strategies have been proposed to achieve better therapeutic outcomes,given their immunosuppressive potential.However,the efficacy and trial designs have varied among the studies,and some research findings appear contradictory due to the challenges in characterizing the in vivo effects of MSCs.This review aims to provide real insights into this clinical entity,emphasizing diagnostic,and therapeutic considerations and generating pathophysiology hypotheses to identify research avenues.The indications and timing for the clinical application of MSCs are still subject to debate.
基金Supported by the National Institute on Aging of the National Institutes of Health under Award No.P30AG010129the UC Davis Alzheimer's Disease Center Pilot Program,No.5R01NS100761-02 and No.1R01NS115860-01A1+1 种基金the Shriners Hospitals for Children Research Grants,No.85108-NCA-19 and No.85135-NCA-21the Shriners Hospitals for Children Postdoctoral Fellowship,No.84705-NCA-19.
文摘Mesenchymal stem/stromal cells(MSCs)are extensively studied as cell-therapy agents for neurological diseases.Recent studies consider exosomes secreted by MSCs as important mediators for MSCs’neuroprotective functions.Exosomes transfer functional molecules including proteins,lipids,metabolites,DNAs,and coding and non-coding RNAs from MSCs to their target cells.Emerging evidence shows that exosomal microRNAs(miRNAs)play a key role in the neuroprotective properties of these exosomes by targeting several genes and regulating various biological processes.Multiple exosomal miRNAs have been identified to have neuroprotective effects by promoting neurogenesis,neurite remodeling and survival,and neuroplasticity.Thus,exosomal miRNAs have significant therapeutic potential for neurological disorders such as stroke,traumatic brain injury,and neuroinflammatory or neurodegenerative diseases and disorders.This review discusses the neuroprotective effects of selected miRNAs(miR-21,miR-17-92,miR-133,miR-138,miR-124,miR-30,miR146a,and miR-29b)and explores their mechanisms of action and applications for the treatment of various neurological disease and disorders.It also provides an overview of state-of-the-art bioengineering approaches for isolating exosomes,optimizing their yield and manipulating the miRNA content of their cargo to improve their therapeutic potential.
基金Supported by the Henan Province Science and Technique Bureau R&D Project,No.222102310228.
文摘Mesenchymal stromal/stem cells(MSCs)are currently applied in regenerative medicine and tissue engineering.Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefits for patients.MSCs derived from either human adult or perinatal tissues have their own unique advantages in their medical practices.Usually,clinical studies are conducted by using of cultured MSCs after thawing or short-term cryopreserved-then-thawed MSCs prior to administration for the treatment of a wide range of diseases and medical disorders.Currently,cryogenically banking perinatal MSCs for potential personalized medicine for later use in lifetime has raised growing interest in China as well as in many other countries.Meanwhile,this has led to questions regarding the availability,stability,consistency,multipotency,and therapeutic efficiency of the potential perinatal MSC-derived therapeutic products after longterm cryostorage.This opinion review does not minimize any therapeutic benefit of perinatal MSCs in many diseases after short-term cryopreservation.This article mainly describes what is known about banking perinatal MSCs in China and,importantly,it is to recognize the limitation and uncertainty of the perinatal MSCs stored in cryobanks for stem cell medical treatments in whole life.This article also provides several recommendations for banking of perinatal MSCs for potentially future personalized medicine,albeit it is impossible to anticipate whether the donor will benefit from banked MSCs during her/his lifetime.
基金Supported by the National Natural Science Foundation of China,Nos.81500207,81670458,and 81470393Shanghai Municipal Health and Family Planning Commission,No.ZY(2018-2020)-FWTX-2007+4 种基金Shanghai Key Medical Discipline for Critical Care Medicine,No.2017zz02017the National Key Research and Development Program of China,No.2017YFA0105600Major Program of Development Fund for Shanghai Zhangjiang National Innovtaion Demonstration Zone,No.ZJ2018-ZD-004the Science and Technology Commission of Shanghai Municipality,No.17431906600and the Top-level Clinical Discipline Project of Shanghai Pudong,No.PWYgf2018-05.
文摘Mesenchymal stem/stromal cells(MSCs)have various properties that make them promising candidates for stem cell-based therapies in clinical settings.These include self-renewal,multilineage differentiation,and immunoregulation.However,recent studies have confirmed that aging is a vital factor that limits their function and therapeutic properties as standardized clinical products.Understanding the features of senescence and exploration of cell rejuvenation methods are necessary to develop effective strategies that can overcome the shortage and instability of MSCs.This review will summarize the current knowledge on characteristics and functional changes of aged MSCs.Additionally,it will highlight cell rejuvenation strategies such as molecular regulation,noncoding RNA modifications,and microenvironment controls that may enhance the therapeutic potential of MSCs in clinical settings.
基金Supported by National Natural Science Foundation of China,No.81703533Natural Science Foundation of Shanghai,No.20ZR1449500+2 种基金Shanghai Jiao Tong University Medical Engineering Cross Fund,No.YG2019GD02Science Technology Development Fund of Shanghai Pudong New Area,No.PKJ2020-Y28Medical Discipline Construction Project of Pudong Health Committee of Shanghai,No.PWYts2021-05.
文摘Osteoporosis is a systemic bone disease,which leads to decreased bone mass and an increased risk of fragility fractures.Currently,there are many anti-resorption drugs and osteosynthesis drugs,which are effective in the treatment of osteoporosis,but their usage is limited due to their contraindications and side effects.In regenerative medicine,the unique repair ability of mesenchymal stem cells(MSCs)has been favored by researchers.The exosomes secreted by MSCs have signal transduction and molecular delivery mechanisms,which may have therapeutic effects.In this review,we describe the regulatory effects of MSCs-derived exosomes on osteoclasts,osteoblasts,and bone immunity.We aim to summarize the preclinical studies of exosome therapy in osteoporosis.Furth-ermore,we speculate that exosome therapy can be a future direction to improve bone health.
文摘Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used MSCs toalleviate COVID-19-associated acute lung injury and cytokine storm, reportedpromising results. However, the evidence came from a case report, case series,and clinical trials with a limited number of participants. Therefore, more studiesare needed to get robust proof of MSC beneficial effects.
文摘Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies,and pretreatment has proven to enhance cell vitality and function.In a recent publication,Li et al explored a new combination of pretreatment condi-tions.Here,we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.
文摘Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.
