Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essent...Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.展开更多
Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal...Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal,due to the short-term action of employed analgesics and their poor adverse effect profile.Due to their regenerative and anti-inflammatory properties,mesenchymal stem cells(MSCs)have been extensively investigated as a potential therapy for OA,and numerous preclinical and clinical studies found a significant improvement in joint pathology and function,pain scores and/or quality of life after administration of MSCs.Only a limited number of studies,however,addressed pain control as the primary end-point or investigated the potential mechanisms of analgesia induced by MSCs.In this paper,we review the evidence reported in literature that support the analgesic action of MSCs in OA,and we summarize the potential mechanisms of these antinociceptive effects.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases.Diabetes mellitus(DM)is a frequently diagnosed chronic diseas...BACKGROUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases.Diabetes mellitus(DM)is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the long-run.DM patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged tissues.MSCs therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease model.AIM To investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of MSCs.METHODS Human adipose tissue-derived MSCs(hAD-MSCs)were seeded in low(5.6 mmol/L of glucose)and high glucose(25 mmol/L of glucose)for 7 d.Cytotoxicity,viability,mitochondrial dynamics,and apoptosis were deplored using specific kits.Western blotting was performed to measure the protein expression of phosphatidylinositol 3-kinase(PI3K),TSC1,and mammalian target of rapamycin(mTOR)in these cells.RESULTS hAD-MSCs cultured in high glucose for 7 d demonstrated marked decrease in their viability,as shown by a significant increase in lactate dehydrogenase(P<0.01)and a significant decrease in Trypan blue(P<0.05)in these cells compared to low glucose control.Mitochondrial membrane potential,indicated by tetramethylrhodamine ethyl ester(TMRE)fluorescence intensity,and nicotinamide adenine dinucleotide(NAD+)/NADH ratio were significantly dropped(P<0.05 for TMRE and P<0.01 for NAD+/NADH)in high glucose exposed hAD-MSCs,indicating disturbed mitochondrial function.PI3K protein expression significantly decreased in high glucose culture MSCs(P<0.05 compared to low glucose)and it was coupled with significant upregulation in TSC1(P<0.05)and downregulation in mTOR protein expression(P<0.05).Mitochondrial complexes I,IV,and V were downregulated profoundly in high glucose(P<0.05 compared to low glucose).Apoptosis was induced as a result of mitochondrial impairment and explained the poor survival of MSCs in high glucose.CONCLUSION High glucose impaired the mitochondrial dynamics and regulatory proteins in hAD-MSCs ensuing their poor survival and high apoptosis rate in hyperglycemic microenvironment.展开更多
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) orcoronavirus disease 2019 (COVID-19) pandemic has exhausted the health systemsin many countries with thousands cases diagnosed daily. The currently use...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) orcoronavirus disease 2019 (COVID-19) pandemic has exhausted the health systemsin many countries with thousands cases diagnosed daily. The currently usedtreatment guideline is to manage the common symptoms like fever and cough,but doesn’t target the virus itself or halts serious complications arising from thisviral infection. Currently, SARS-CoV-2 exhibits many genetic modulations whichhave been associated with the appearance of highly contagious strains. Thenumber of critical cases of COVID-19 increases markedly, and many of theinfected people die as a result of respiratory failure and multiple organ dysfunction. The regenerative potential of mesenchymal stem cells (MSCs) has beenextensively studied and confirmed. The impressive immunomodulation and antiinflammatoryactivity of MSCs have been recognized as a golden opportunity forthe treatment of COVID-19 and its associated complications. Moreover, MSCsregenerative and repairing abilities have been corroborated by many studies withpositive outcomes and high recovery rates. Based on that, MSCs infusion could bean effective mechanism in managing and stemming the serious complications andmultiple organ failure associated with COVID-19. In the present review, wediscuss the commonly reported complications of COVID-19 viral infection and theestablished and anticipated role of MSCs in managing these complications.展开更多
The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative di...The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative diseases.MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases.Herein,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.展开更多
Mesenchymal stem cells(MSCs)have gained wide-ranging reputation in the medical research community due to their promising regenerative abilities.MSCs can be isolated from various resources mostly bone marrow,Adipose ti...Mesenchymal stem cells(MSCs)have gained wide-ranging reputation in the medical research community due to their promising regenerative abilities.MSCs can be isolated from various resources mostly bone marrow,Adipose tissues and Umbilical cord.Huge advances have been achieved in comprehending the possible mechanisms underlying the therapeutic functions of MSCs.Despite the proven role of MSCs in repairing and healing of many disease modalities,many hurdles hinder the transferring of these cells in the clinical settings.Among the most reported problems encountering MSCs therapy in vivo are loss of tracking signal post-transplantation,insufficient migration,homing and engraftment postinfusion,and undesirable differentiation at the site of injury.Magnetic nanoparticles(MNPs)have been used widely for various biomedical applications.MNPs have a metallic core stabilized by an outer coating material and their magnetic properties can be modulated by an external magnetic field.These magnetic properties of MNPs were found to enhance the quality of diagnostic imaging procedures and can be used to create a carrying system for targeted delivery of therapeutic substances mainly drug,genes and stem cells.Several studies highlighted the advantageous outcomes of combining MSCs with MNPs in potentiating their tracking,monitoring,homing,engraftment and differentiation.In this review,we will discuss the role of MNPs in promoting the therapeutic profile of MSCs which may improve the success rate of MSCs transplantation and solve many challenges that delay their clinical applicability.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory properties.Serial passage and stress factors may affect the biological char...BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory properties.Serial passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized yet.AIM To investigate the effects of stress factors(high glucose and severe hypoxia)on the biological characteristics of MSCs at different passages,in order to optimize the therapeutic applications of MSCs.METHODS In this study,we investigated the impact of two stress conditions;severe hypoxia and high glucose on human adipose-tissue derived MSCs(hAD-MSCs)at passages 6(P6),P8,and P10.Proliferation,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,respectively.RESULTS Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control,while the extent of senescence did not change significantly under stress conditions.At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6.Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage,while no change in apoptosis was observed.On the other hand,MSCs cultured under hypoxia showed decreased senescence,increased apoptosis and no significant change in proliferation when compared to the same conditions at P8.CONCLUSION These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages,and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.展开更多
文摘Mesenchymalstemcells(MSCs)areidealcandidatesfortreatingmanycardiovasculardiseases.MSCscanmodify the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart function.MSCs can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental pulp.MSCs from various sources differ in their regenerative and therapeutic abilities for cardiovascular disorders.In this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.
文摘Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health burden.Pain is the most common and bothersome presentation of OA,but its treatment is still suboptimal,due to the short-term action of employed analgesics and their poor adverse effect profile.Due to their regenerative and anti-inflammatory properties,mesenchymal stem cells(MSCs)have been extensively investigated as a potential therapy for OA,and numerous preclinical and clinical studies found a significant improvement in joint pathology and function,pain scores and/or quality of life after administration of MSCs.Only a limited number of studies,however,addressed pain control as the primary end-point or investigated the potential mechanisms of analgesia induced by MSCs.In this paper,we review the evidence reported in literature that support the analgesic action of MSCs in OA,and we summarize the potential mechanisms of these antinociceptive effects.
文摘BACKGROUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases.Diabetes mellitus(DM)is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the long-run.DM patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged tissues.MSCs therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease model.AIM To investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of MSCs.METHODS Human adipose tissue-derived MSCs(hAD-MSCs)were seeded in low(5.6 mmol/L of glucose)and high glucose(25 mmol/L of glucose)for 7 d.Cytotoxicity,viability,mitochondrial dynamics,and apoptosis were deplored using specific kits.Western blotting was performed to measure the protein expression of phosphatidylinositol 3-kinase(PI3K),TSC1,and mammalian target of rapamycin(mTOR)in these cells.RESULTS hAD-MSCs cultured in high glucose for 7 d demonstrated marked decrease in their viability,as shown by a significant increase in lactate dehydrogenase(P<0.01)and a significant decrease in Trypan blue(P<0.05)in these cells compared to low glucose control.Mitochondrial membrane potential,indicated by tetramethylrhodamine ethyl ester(TMRE)fluorescence intensity,and nicotinamide adenine dinucleotide(NAD+)/NADH ratio were significantly dropped(P<0.05 for TMRE and P<0.01 for NAD+/NADH)in high glucose exposed hAD-MSCs,indicating disturbed mitochondrial function.PI3K protein expression significantly decreased in high glucose culture MSCs(P<0.05 compared to low glucose)and it was coupled with significant upregulation in TSC1(P<0.05)and downregulation in mTOR protein expression(P<0.05).Mitochondrial complexes I,IV,and V were downregulated profoundly in high glucose(P<0.05 compared to low glucose).Apoptosis was induced as a result of mitochondrial impairment and explained the poor survival of MSCs in high glucose.CONCLUSION High glucose impaired the mitochondrial dynamics and regulatory proteins in hAD-MSCs ensuing their poor survival and high apoptosis rate in hyperglycemic microenvironment.
文摘The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) orcoronavirus disease 2019 (COVID-19) pandemic has exhausted the health systemsin many countries with thousands cases diagnosed daily. The currently usedtreatment guideline is to manage the common symptoms like fever and cough,but doesn’t target the virus itself or halts serious complications arising from thisviral infection. Currently, SARS-CoV-2 exhibits many genetic modulations whichhave been associated with the appearance of highly contagious strains. Thenumber of critical cases of COVID-19 increases markedly, and many of theinfected people die as a result of respiratory failure and multiple organ dysfunction. The regenerative potential of mesenchymal stem cells (MSCs) has beenextensively studied and confirmed. The impressive immunomodulation and antiinflammatoryactivity of MSCs have been recognized as a golden opportunity forthe treatment of COVID-19 and its associated complications. Moreover, MSCsregenerative and repairing abilities have been corroborated by many studies withpositive outcomes and high recovery rates. Based on that, MSCs infusion could bean effective mechanism in managing and stemming the serious complications andmultiple organ failure associated with COVID-19. In the present review, wediscuss the commonly reported complications of COVID-19 viral infection and theestablished and anticipated role of MSCs in managing these complications.
文摘The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative diseases.MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases.Herein,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.
文摘Mesenchymal stem cells(MSCs)have gained wide-ranging reputation in the medical research community due to their promising regenerative abilities.MSCs can be isolated from various resources mostly bone marrow,Adipose tissues and Umbilical cord.Huge advances have been achieved in comprehending the possible mechanisms underlying the therapeutic functions of MSCs.Despite the proven role of MSCs in repairing and healing of many disease modalities,many hurdles hinder the transferring of these cells in the clinical settings.Among the most reported problems encountering MSCs therapy in vivo are loss of tracking signal post-transplantation,insufficient migration,homing and engraftment postinfusion,and undesirable differentiation at the site of injury.Magnetic nanoparticles(MNPs)have been used widely for various biomedical applications.MNPs have a metallic core stabilized by an outer coating material and their magnetic properties can be modulated by an external magnetic field.These magnetic properties of MNPs were found to enhance the quality of diagnostic imaging procedures and can be used to create a carrying system for targeted delivery of therapeutic substances mainly drug,genes and stem cells.Several studies highlighted the advantageous outcomes of combining MSCs with MNPs in potentiating their tracking,monitoring,homing,engraftment and differentiation.In this review,we will discuss the role of MNPs in promoting the therapeutic profile of MSCs which may improve the success rate of MSCs transplantation and solve many challenges that delay their clinical applicability.
基金Supported by the Deanship of Scientific Research,Yarmouk University,Jordan,No.73/2022.
文摘BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory properties.Serial passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized yet.AIM To investigate the effects of stress factors(high glucose and severe hypoxia)on the biological characteristics of MSCs at different passages,in order to optimize the therapeutic applications of MSCs.METHODS In this study,we investigated the impact of two stress conditions;severe hypoxia and high glucose on human adipose-tissue derived MSCs(hAD-MSCs)at passages 6(P6),P8,and P10.Proliferation,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,respectively.RESULTS Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control,while the extent of senescence did not change significantly under stress conditions.At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6.Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage,while no change in apoptosis was observed.On the other hand,MSCs cultured under hypoxia showed decreased senescence,increased apoptosis and no significant change in proliferation when compared to the same conditions at P8.CONCLUSION These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages,and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.
