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Mesenchymal stem cells derived secretome as an innovative cell-free therapeutic approach

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BIOCELL 2022年第4期46卷 907-911页

作者： EJLAL ABU-EL-rUB ramada r.khasawneh FATIMAH A.ALMAHASNEH HANA M.ZEGALLAI Department of Basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbid21163Jordan Physiology and Pathophysiology Faculty of MedicineUniversity of ManitobaWinnipegR3E0W2Canada Department of Pharmacology&Therapeutics University of ManitobaWinnipegR3E0W2Canada DrEAM Children’s Hospital Research Institute of ManitobaWinnipegR3E0W2Canada

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 *** secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic ***,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.

关键词： Mesencyhmal stem cells Secretome Immuno-modulation Cytokines Growth factors

Effects of high glucose and severe hypoxia on the biological behavior of mesenchymal stem cells at various passages

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World Journal of Stem Cells 2024年第4期16卷 434-443页

作者： Fatimah Almahasneh Ejlal Abu-El-rub ramada r.khasawneh rawan Almazari Department of Basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbid 21163Jordan

BACKGrOUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory *** passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized *** 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 *** 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 ***,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,*** 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 *** 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 *** 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 *** 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 *** 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.

关键词： Mesenchymal stem cells High glucose Hypoxia Stressful microenvironment Serial passage Senescence Apoptosis

Prodigious therapeutic effects of combining mesenchymal stem cells with magnetic nanoparticles

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World Journal of Stem Cells 2022年第7期14卷 513-526页

作者： Ejlal Abu-El-rub ramada r.khasawneh Fatimah Almahasneh Department of Physiology and Pathophysiology Yarmouk UniversityIrbid 21163Jordan Department of Anatomy and Histology Yarmouk UniversityIrbid 21163Jordan

Mesenchymal stem cells(MSCs)have gained wide-ranging reputation in the medical research community due to their promising regenerative *** can be isolated from various resources mostly bone marrow,Adipose tissues and Umbilical *** advances have been achieved in comprehending the possible mechanisms underlying the therapeutic functions of *** the proven role of MSCs in repairing and healing of many disease modalities,many hurdles hinder the transferring of these cells in the clinical *** 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 *** nanoparticles(MNPs)have been used widely for various biomedical *** have a metallic core stabilized by an outer coating material and their magnetic properties can be modulated by an external magnetic *** 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 *** studies highlighted the advantageous outcomes of combining MSCs with MNPs in potentiating their tracking,monitoring,homing,engraftment and *** 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.

关键词： Mesenchymal stem cells Magnetic nanoparticles Tracking Homing Migration Differentiation

Mechanisms of analgesic effect of mesenchymal stem cells in osteoarthritis pain

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World Journal of Stem Cells 2023年第4期15卷 196-208页

作者： Fatimah Almahasneh Ejlal Abu-El-rub ramada r.khasawneh Basic Medical Sciences Faculty of Medicine-Yarmouk UniversityIrbid 21163Jordan

Osteoarthritis(OA)is the most common musculoskeletal disease,and it is a major cause of pain,disability and health *** 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 *** 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 *** a limited number of studies,however,addressed pain control as the primary end-point or investigated the potential mechanisms of analgesia induced by *** 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.

关键词： Osteoarthritis Pain Inflammation Mesenchymal stem cells regeneration Analgesic mechanisms

Human mesenchymal stem cells exhibit altered mitochondrial dynamics and poor survival in high glucose microenvironment

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World Journal of Stem Cells 2023年第12期15卷 1093-1103页

作者： Ejlal Abu-El-rub Fatimah Almahasneh ramada r.khasawneh Ayman Alzu'bi Doaa Ghorab rawan Almazari Huthaifa Magableh Ahmad Sanajleh Haitham Shlool Mohammad Mazari Noor S Bader Joud Al-Momani Department of Basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbid 21163Jordan Department of Pathology Faculty of MedicineMansoura UniversityMansoura 35516Egypt Department of Basic Medical Sciences Yarmouk UniversityIrbid 21163Jordan

BACKGrOUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic *** mellitus(DM)is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the *** patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged *** therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease *** To investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of *** 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 ***,viability,mitochondrial dynamics,and apoptosis were deplored using specific *** blotting was performed to measure the protein expression of phosphatidylinositol 3-kinase(PI3K),TSC1,and mammalian target of rapamycin(mTOr)in these *** hAD-MSCs cultured in high glucose for 7 d demonstrated marked decrease in their viability,as shown by a significant increase in lactate dehydrogenase(Prease in Trypan blue(Pred to low glucose *** membrane potential,indicated by tetramethylrhodamine ethyl ester(TMrE)fluorescence intensity,and nicotinamide adenine dinucleotide(NAD+)/NADH ratio were significantly dropped(Pr TMrE and Pr NAD+/NADH)in high glucose exposed hAD-MSCs,indicating disturbed mitochondrial ***3K protein expression significantly decreased in high glucose culture MSCs(Pred to low glucose)and it was coupled with significant upregulation in TSC1(Pregulation in mTOr protein expression(Prial complexes I,IV,and V were downregul

关键词： Mesenchymal stem cells High glucose Mitochondrial dynamics Apoptosis Poor survival Phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway

Mesenchymal stem cells and COVID-19: What they do and what they can do

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World Journal of Stem Cells 2021年第9期13卷 1318-1337页

作者： Ejlal Abu-El-rub ramada r.khasawneh Fatimah Almahasneh Zaid Altaany Nesreen Bataineh Hana Zegallai Saravanan Sekaran Department of Physiology and Pathophysiology University of ManitobaWinnipeg R2H2A6Canada Department of Physiology and Pathophysiology Basic Medical SciencesYarmouk UniversityIRBID 21163Jordan Department of Anatomy and Histology Basic Medical SciencesYarmouk UniversityIRBID 21163Jordan Department of Physiology and Pharmacology Basic Medical SciencesYarmouk UniversityIRBID 21163Jordan Department of Biochemistry and Genetics Basic Medical SciencesYarmouk UniversityIRBID 21163Jordan Department of Pathology Basic Medical SciencesYarmouk UniversityIRBID 21163Jordan Department of Pharmacology and Therapeutics University of ManitobaWinnipeg R2H2A6Canada Department of Pharmacology Saveetha Dental College and Hospitals to be UniversityChennai 600077India

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.

关键词： SArS-CoV-2 COVID-19 Mesenchymal stem cells Inflammation Acute respiratory distress syndrome Pulmonary fibrosis Pneumonia renal injury Cardiovascular diseases regeneration Anti-inflammatory