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Nicorandil potentiates sodium butyrate induced preconditioning of neurons and enhances their survival upon subsequent treatment with H_(2)O_(2)

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Translational Neurodegeneration 2017年第1期6卷 291-299页

作者： Parisa Tabeshmehr haider kh husnain Mahin Salmannejad Mahsa Sani Seyed Mojtaba Hosseini Mohammad Hossein khorraminejad Shirazi Student Research Committee Shiraz University of Medical SciencesShirazIran Cell&Molecular Medicine Student Research Group Medical FacultyShiraz University of Medical SciencesShirazIran Department of Basic Sciences SRURiyadhSaudi Arabia Stem Cell Laboratory Department of AnatomyShiraz University of Medical SciencesShirazIran

Background:Extensive loss of donor neural stem cell(NSCs)due to ischemic stress and low rate of differentiation at the site of cell graft are two of the major issues that hamper optimal outcome in NSCs transplantation *** that histone deacetylases(HDACs)modulate various cellular processes by deacetylating histones and non-histone proteins,we hypothesized that combined treatment with small molecules,sodium butyrate(NaB;a known HDAC inhibitor)and nicorandil,will enhance the rate neuronal differentiation of NSCs besides their preconditioning to resist oxidative ***:NSCs derived from 14-day old Sprague Dawley rat ganglion eminence were characterized for tri-lineage *** with 1 mM NaB significantly changed their culture characteristics while continuous treatment for 10 days enhanced their neural *** treatment also preconditioned the cells for their resistance to oxidative ***:The highest rate of neural differentiation and preconditioning effect was achieved when the NSCs were treated concomitantly with NaB and *** proliferation assay showed that concomitant treatment with NaB and nicorandil retarded their rate of ***:These data conclude that preconditioning of NSCs with NaB and nicorandil effectively enhances their differentiation capacity besides preconditioning the cells to support their survival under ischemic conditions.

关键词： Apoptosis Neural stem cells Oxidative stress Preconditioning

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Priming mesenchymal stem cells to develop “super stem cells”

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World Journal of Stem Cells 2024年第6期16卷 623-640页

作者： khawaja husnain haider Department of Basic Sciences Sulaiman AlRajhi UniversityAlQaseem 52736Saudi Arabia

The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment,genetic manipulation,and chemical and pharmacological treatment,each strategy having advantages and *** of these pre-treatment protocols are *** editorial is a continuum of Li et al’s published article and Wan et al’s editorial focusing on the significance of pre-treatment strategies to enhance their stemness,immunoregulatory,and immunosuppressive *** have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and *** a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells(MSCs),pre-treatment based on the mechanistic understanding is expected to develop“Super MSCs”,which will create a transformative shift in MSC-based therapies in clinical settings,potentially revolutionizing the *** optimized,the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop“super stem cells”with augmented stemness,functionality,and reparability for diverse clinical applications with better outcomes.

关键词： Cell survival Cell therapy Preconditioning Pre-treatment Stem cells Super stem cells

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Melatonin-based priming of stem cells to alleviate oxidative stress

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World Journal of Stem Cells 2024年第11期16卷 985-989页

作者： khawaja husnain haider Department of Basic Sciences Sulaiman Al Rajhi UniversityAl Bukairiyah 51941AlQaseemSaudi Arabia

Stem cell expansion in vitro and transplantation in the cytokine-rich proinflammatory milieu in the injured tissue generate immense oxidative stress that interferes with the cells’survival,stemness,and *** cell priming has gained popularity to overcome these *** melatonin’s oxidative-scavenging properties,Gu et al have used periodontal ligament stem cells cultured under oxidative stress as an in vitro model to study the cytoprotective effects of *** letter to the editor delves into melatonin-induced stem cell priming and the underlying molecular mechanism,focusing on the intriguing role of Yesassociated protein signaling in alleviating oxidative *** stress the importance of understanding the distinction between in vitro and in vivo oxidative stress conditions,a crucial aspect of stem cell research that invokes a sense of critical thinking in the *** study by Gu et al presents a novel approach to oxidative stress management,offering exciting possibilities for future research and applications.

关键词： Melatonin Oxidative stress Priming Stem cells Yes-associated protein

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Defining lung cancer stem cells exosomal payload of miRNAs in clinical perspective

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World Journal of Stem Cells 2020年第6期12卷 406-421页

作者： Beatrice Aramini Valentina Masciale khawaja husnain haider Department of Medical and Surgical Sciences University of Modena and Reggio EmiliaModena 41124Italy MPharm PhDSulaiman AlRajhi UniveristyAlQaseem 52736Saudi Arabia

Since the first publication regarding the existence of stem cells in cancer[cancer stem cells(CSCs)]in 1994,many studies have been published providing in-depth information about their biology and *** research has paved the way in terms of appreciating the role of CSCs in tumour aggressiveness,progression,recurrence and resistance to cancer *** CSCs for cancer therapy has still not progressed to a sufficient degree,particularly in terms of exploring the mechanism of dynamic interconversion between CSCs and *** the CSC scenario,the problem of cancer dissemination has been analyzed indepth with the identification and isolation of microRNAs(miRs),which are now considered to be compelling molecular markers in the diagnosis and prognosis of tumours in general and specifically in patients with non-small cell lung *** release of miRs via“exosomes”(small membrane vesicles(30-100 nm),the derivation of which lies in the luminal membranes of multi-vesicular bodies)released by fusion with the cell membrane is gaining *** exosomes play a significant role in maintaining a dynamic equilibrium state between CSCs and non-CSCs and their mechanism of activity is as yet *** studies on CSC-related exosomes will provide new perspectives for precision-targeted treatment strategies.

关键词： Cancer Cancer stem cells Exosomes Lungs miRNA Microvesicles Nonsmall cell lung cancer

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Cellular preconditioning and mesenchymal stem cell ferroptosis

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World Journal of Stem Cells 2024年第2期16卷 64-69页

作者： Doaa Hussein Zineldeen Mazhar Mushtaq khawaja husnain haider Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia Department of Medical Biochemistry and Molecular Biology Faculty of MedicineTanta UniversityTanta 6632110Egypt

In this editorial,we comment on the article published in the recent issue of the World Journal of Stem *** focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionineγ-lyase/hydrogen sulfide(H_(2)S)pathway as a novel approach to treat vascular disorders,particularly pulmonary *** stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh,unfavorable microenvironment of the injured *** also secrete various paracrine factors against apoptosis,necrosis,and ferroptosis to enhance cell ***,a regulated form of cell death characterized by iron accumulation and oxidative stress,has been implicated in various pathologies encompassing dege-nerative disorders to *** lipid peroxidation cascade initiates and sustains ferroptosis,generating many reactive oxygen species that attack and damage multiple cellular *** these intertwined mechanisms provi-des significant insights into developing therapeutic modalities for ferroptosis-related *** editorial primarily discusses stem cell preconditioning in modulating ferroptosis,focusing on the cystathionase gamma/H_(2)S ferroptosis *** presents a significant challenge in mesenchymal stem cell(MSC)-based therapies;hence,the emerging role of H_(2)S/cystathionase gamma/H_(2) S signaling in abrogating ferroptosis provides a novel option for therapeutic *** research into understanding the precise mechanisms of H_(2)S-mediated cytoprotection against ferroptosis is warranted to enhance the thera-peutic potential of MSCs in clinical settings,particularly vascular disorders.

关键词： Cell survival Cell therapy Hydrogen sulfide Ferroptosis Preconditioning Stem cells Umbilical cord

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Skeletal myoblast based delivery of angiogenic growth factors:a comparison between angiopoietin-1 and VEGF gene delivery for therapeutic angiogenesis in the heart

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Journal of Geriatric Cardiology 2006年第3期3卷 152-160页

作者： husnain kh haider In-Chin Song Peter K Law Eugene KW Sim Department of Pathology and Laboratory Medicine University of Cincinnati Ohio United States Departmet of Experimental Surgery Singapore General Hospital Singapore Cell Transplants Singapore Pte Ltd Singapore Department of Surgery National University of Singapore Singapore & Gleneagles JPMC Cardiac Center Brunei Darussalam Singapore

Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction was created in 28 female swine by coronary artery ligation. The animals were randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced SkM transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced SkM transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced SkM (n=8). Three weeks later, 5 ml DMEM containing 3×108 SkM carrying exogenous genes were intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted at 2, 6 and 12 weeks after transplantation for histological studies. Results Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von Willebrand factor-VIII (vWF-VIII) at low power field (×100) was 57.13±11.85 in group-3 at 6 weeks and declined to 32.1±5.21 at 12 weeks, while it was 39.9±10.26 at 6 weeks and increased to 45.14±6.54 at 12 weeks in group-4. The mature blood vessel index was highest in group- 4 at 6 and 12 weeks after transplantation. The regional blood flow in the center and peri-infarct area was significantly increased in animals of groups-3 and -4. Conclusions SkM carrying either hVEGF165 or Ang-1 induced neovascularization with increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.

关键词： therapeutic angiogenesis skeletal myoblasts vascular endothelial growth factor-165 angiopoietin-1 myocardial infarction

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High glucose microenvironment and human mesenchymal stem cell behavior

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World Journal of Stem Cells 2024年第3期16卷 237-244页

作者： Muhammad Abdul Mateen Nouralsalhin Alaagib khawaja husnain haider Basic Sciences Sulaiman AlRajhi UniversityAlQaseem 52736Saudi Arabia Cellular and Molecular Pharmacology Sulaiman AlRajhi Medical SchoolAl Bukairiyah 51941Saudi Arabia

High glucose(HG)culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells,analogous to any other cell type in our *** interferes with diverse signaling pathways,*** target of rapamycin(mTOR)-phosphoinositide 3-kinase(PI3K)-Akt signaling,to impact physiological cellular functions,leading to low cell survival and higher cell apoptosis *** elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells(MSCs),a recent study has shown that HG culture conditions dysregulate mTORPI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential(MtMP)that lowers ATP *** organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural *** of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in *** previous studies have also reported altered mitochondrial membrane polarity(causing hyperpolarization)and reduced mitochondrial cell mass,leading to perturbed mitochondrial *** hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria,altering their bioenergetics and reducing their capacity to produce *** are significant data,as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based ***,MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor sur-vival rates and increased rates of post engraftment *** hypergly-cemia alters the bioenergetics of donor MSCs,rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs i

关键词： Adipose tissue Apoptosis Bioenergetics Cell survival Cell therapy Hyperglycemia Mitochondria Mesenchymal stem cells Stem cells

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Mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes

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World Journal of Stem Cells 2024年第5期16卷 467-478页

作者： Mazhar Mushtaq Doaa Hussein Zineldeen Muhammad Abdul Mateen khawaja husnain haider Department of Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia Medical Biochemistry and Molecular Biology Department Faculty of MedicineTanta UniversityTanta 6632110Egypt

Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal ***,structural and functional recovery is a senile process involving multifaceted cellular and molecular *** contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large *** advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic *** recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

关键词： Exosome Mesenchymal stem cells Nerve injury Stem cells Secretome Regeneration

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Tissue-source effect on mesenchymal stem cells as living biodrugs for heart failure:Systematic review and meta-analysis

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World Journal of Cardiology 2024年第8期16卷 469-483页

作者： Moaz Safwan Mariam Safwan Bourgleh Mohamed Aldoush khawaja husnain haider Department of Basic Sciences Sulaiman Al Rajhi UniversityAl Bukairiyah 51941Saudi Arabia

BACKGROUND Mesenchymal stem cells(MSCs),as living biodrugs,have entered advanced phases of clinical assessment for cardiac function restoration in patients with myocardial infarction and heart *** MSCs are available from diverse tissue sources,bone-marrow-derived MSCs(BM-MSCs)remain the most wellstudied cell type,besides umbilical-cord-derived MSCs(UC-MSCs).The latter offers advantages,including noninvasive availability without ethical *** To compare the safety and efficacy of BM-MSCs and UC-MSCs in terms of left ventricular ejection fraction(LVEF),6-min walking distance(6MWD),and major adverse cardiac events(MACEs).METHODS Five databases were systematically searched to identify randomized controlled trials(RCTs).Thirteen RCTs(693 patients)were included using predefined eligibility *** mean differences and odds ratio(OR)for the changes in the estimated treatment *** UC-MSCs significantly improved LVEF vs controls by 5.08%[95%confidence interval(CI):2.20%-7.95%]at 6 mo and 2.78%(95%CI:0.86%-4.70%)at 12 ***,no significant effect was observed for BM-MSCs vs *** significant changes were observed in the 6MWD with either of the two cell ***,no differences were observed for MACEs,except rehospitalization rates,which were lower only with BM-MSCs(odds ratio 0.48,95%CI:0.24-0.97)vs *** UC-MSCs significantly improved LVEF compared with *** advant-Safwan M et ***-source and MSCs as living biodrugs ageous characteristics position them as a promising alternative to MSC-based therapy.

关键词： Cardiovascular disease Heart disease Mesenchymal stem cells Umbilical cord stem cells

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Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients

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World Journal of Cardiology 2024年第6期16卷 339-354页

作者： Muhammad Candragupta Jihwaprani Idris Sula Mohamed Ahmed Charbat khawaja husnain haider Basic Sciences SRCAl Bukayriyah 52736AlQaseemSaudi Arabia

BACKGROUND Mesenchymal stem cells(MSCs)as living biopharmaceuticals with unique properties,i.e.,stemness,viability,phenotypes,paracrine activity,etc.,need to be administered such that they reach the target site,maintaining these properties unchanged and are retained at the injury site to participate in the repair *** of delivery(RoD)remains one of the critical determinants of safety and *** study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure(HF)based on phase II randomized clinical trials(RCTs).We hypothesize that the RoD modulates the safety and efficacy of MSCbased therapy and determines the outcome of the *** To investigate the effect of RoD of MSCs on safety and efficacy in HF *** RCTs were retrieved from six *** endpoints included mortality and serious adverse events(SAEs),while efficacy outcomes encompassed changes in left ventricular ejection fraction(LVEF),6-minute walk distance(6MWD),and pro-B-type natriuretic peptide(pro-BNP).Subgroup analyses on RoD were performed for all study *** Twelve RCTs were ***,MSC therapy demonstrated a significant decrease in mortality[relative risk(RR):0.55,95%confidence interval(95%CI):0.33-0.92,P=0.02]compared to control,while SAE outcomes showed no significant difference(RR:0.84,95%CI:0.66-1.05,P=0.11).RoD subgroup analysis revealed a significant difference in SAE among the transendocardial(TESI)injection subgroup(RR=0.71,95%CI:0.54-0.95,P=0.04).The pooled weighted mean difference(WMD)demonstrated an overall significant improvement of LVEF by 2.44%(WMD:2.44%,95%CI:0.80-4.29,P value≤0.001),with only intracoronary(IC)subgroup showing significant improvement(WMD:7.26%,95%CI:5.61-8.92,P≤0.001).Furthermore,the IC delivery route significantly improved 6MWD by 115 m(WMD=114.99 m,95%CI:91.48-138.50),*** biochemical efficacy outcomes,only the IC subgroup showed a significant reduction in pro-

关键词： Clinical trial Heart failure Mesenchymal stem cells Living biodrug Meta-analysis Stem cells Systematic review

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