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

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

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Therapeutic and regenerative potential of different sources of mesenchymal stem cells for cardiovascular diseases

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BIOCelL 2024年第4期48卷 559-569页

作者： YARA ALZGHOUL HALA J.BANI ISSA AHMAD K.SANAJLEH TAQWA ALABDUH FATIMAH RABABAH MAHA AL-SHDAIFAT ejlal abu-el-rub FATIMAH ALMAHASNEH RAMADA R.KHASAWNEH AYMAN ALZU’BI HUTHAIFA MAGABLEH Department of Basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbidJordan

Mesenchymalstemcells(MSCs)*** the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart *** can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental *** from various sources differ in their regenerative and therapeutic abilities for cardiovascular *** 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.

关键词： Bone marrow mesenchymal stem cells Adipose tissue mesenchymal stem cells Dental pulp stem cells Umbilical cord mesenchymal stem cells Cardiomyocytes Regeneration Myocardial infarction Mesenchymal stem cells Differentiation Immunomodulation

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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

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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

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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

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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

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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(Pells compared to low glucose *** 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 ***3K 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 downregul

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

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兔NMU及其受体：cDNA克隆、表达及热应激对其表达的影响

兔NMU及其受体：cDNA克隆、表达及热应激对其表达的影响

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作者： ejlal Ahmed Mohammed Adam 南京农业大学

学位级别：硕士

Neuromedin U(NMU)在结构上是一个高度保守的神经肽,最初分离自猪的脊髓,有NMU-25和NMU-8两种。NMU在胃肠道(GI)等外周组织器官和中枢神经系统(CNS)均有分布。NMU能与两个G蛋白偶联受体(NMU-R1和NMU-R2)结合而发挥作用,NMU-R1主要在外... 详细信息

Neuromedin U(NMU)在结构上是一个高度保守的神经肽,最初分离自猪的脊髓,有NMU-25和NMU-8两种。NMU在胃肠道(GI)等外周组织器官和中枢神经系统(CNS)均有分布。NMU能与两个G蛋白偶联受体(NMU-R1和NMU-R2)结合而发挥作用,NMU-R1主要在外周组织器官内表达,而NMU-R2主要在中枢神经系统中表达。NMU及其受体在体内多种组织器官中的表达,赋予了其众多的功能,具有刺激平滑肌收缩、调节摄食和能量平衡、影响HPA轴、应激和免疫等生物学作用。然而,NMU目前的研究主要集中于人类,大鼠,小鼠和猪等,有关兔NMU及其受体的研究文献中鲜见报道。因此,我们用RT-PCR方法研究了兔NMU及其受体基因的克隆和表达,以及热应激对下丘脑、垂体、肾上腺和睾丸NMU、NMU-R1和NMU-R2mRNA表达的影响。研究结果如下:(1)兔NMU、NMU-R1和NMU-R2的基因克隆本文用PCR方法克隆了兔NMU、NMU-R1和NMU-R2基因片段,其大小分别为443,366和203 bp,并将基因序列提交到GenBank数据库(GenBank ID:kp276160.1,km-236787.1 和 km-236788.1)。(2)兔NMU及其受体氨基酸序列的生物信息学软件分析将本文克隆的兔NMU、NMU-R1和NMU-R2核苷酸序列与其他物种如人类、猪、鼠、牛、绵羊和大鼠相比有很高的同源性,分别为(83%,80%,78%,83%,80%,78%),(87%,84%,81%,80%,86%,80%)和(85%,89%,80%,83%,89%,82%);所预测的氨基酸序列同源性分别为(84%,75%,73%,73%,74%,72%),(84%,78%,75%,84%,83%,75%)和(87%,90%,75%,87%,88%,76%)。兔NMU-R1和NMU-R2氨基酸序列有一个典型的G蛋白偶联受体跨膜结构。NMU、NMU-R1和NMU-R2基因分别定位于第2号、3号和1号染色体上。(3)NMU、NMU-R1和NMU-R2基因在兔体内的表达RT-PCR结果表明,NMU、NMU-R1和NMU-R2 mRNA在中枢神经系统和外周组织器官均有表达,NMU mRNA在外周组织中表达更丰富。NMU mRNA在回肠、睾丸、肝、直肠和下丘脑高表达,在十二指肠、海马、结肠、腮腺和肾上腺中等表达,在研究的其他组织低表达。NMU-R1 mRNA主要在胃肠道表达,如肝、结肠、回肠、盲肠和圆小囊,在脑桥、下丘脑和脊髓中等表达,在小脑低表达。NMU-R2 mRNA在下丘脑、脊髓、小脑、海马、脾、肾、结肠、回肠、下颌腺、腮腺和肾上腺高表达,在空肠、圆小囊、胃和子宫中等表达,在其他研究的组织低表达。(4)热应激对NMU、NMU-R1和NMU-R2 mRNA表达的影响实时荧光定量PCR结果显示,热应激后,NMU、NMU-R1和NMU-R2mRNA在下丘脑、垂体、肾上腺和睾丸均有表达,但其表达变化的模式不尽相同,下丘脑NMU,NMU-R1和NMU-R2 mRNA表达上调的变化早于垂体、肾上腺和睾丸,以便对应激作出迅速的反应,进而调节HPA轴的功能。本研究为进一步研究兔NMU及其受体的生理功能及机制提供了实验数据。

关键词：兔 NMU NMU-R1 NMU-R2 克隆序列分析基因表达热应激

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兔神经介素U及其受体的基因克隆和组织表达的研究

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畜牧与兽医 2017年第1期49卷 39-44页

作者： ejlal Ahmed Mohammed Adam 马志禹李翔李晓亮雷治海南京农业大学动物医学院江苏南京210095

神经介素U(NMU)是从猪脊髓分离得到的一种神经肽,主要为NMU-25和NMU-8。NMU通过与其2个G蛋白偶联受体(NMU-R1和NMU-R2)结合而发挥作用。本文用RT-PCR方法克隆了兔NMU及其受体基因片段,分析了其结构特点,研究其在兔体内的表达分布。克隆... 详细信息

神经介素U(NMU)是从猪脊髓分离得到的一种神经肽,主要为NMU-25和NMU-8。NMU通过与其2个G蛋白偶联受体(NMU-R1和NMU-R2)结合而发挥作用。本文用RT-PCR方法克隆了兔NMU及其受体基因片段,分析了其结构特点,研究其在兔体内的表达分布。克隆了兔NMU、NMU-R1和NMU-R2基因片段,其大小分别为443,366和203 bp,并将基因序列提交到Gen Bank数据库(Gen Bank ID:kp276160.1,km-236787.1和km-236788.1),表明克隆的兔NMU基因片段核苷酸序列与其他物种如大鼠、猪、牛和人相比有较高的同源性(78%~83%),NMU-R1基因核苷酸序列同源性为80%~87%,NMU-R2基因核苷酸序列同源性为82%~89%。兔NMU-R1和NMU-R2具有G蛋白偶联受体的跨膜结构。NMU、NMU-R1和NMU-R2基因分别定位于第2号、3号和1号染色体上。此外,NMU、NMU-R1和NMU-R2 mRNA在兔体内广泛表达。试验结果为深入研究NMU及其受体的生理功能奠定了基础。

关键词：兔神经介素U NMU-R1 NMU-R2 基因克隆基因表达

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