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Hepatic stem cells: A viable approach for the treatment of liver cirrhosis

World Journal of Stem Cells 2015年第5期7卷 860-865页

作者： Md Aejaz Habeeb sandeep kumar vishwakarma Avinash Bardia Aleem Ahmed Khan Center for Liver Research and Diagnostics Deccan College of Medical Sciences

Liver cirrhosis is characterized by distortion of liver architecture, necrosis of hepatocytes and regenerative nodules formation leading to cirrhosis. Various types of cell sources have been used for the management and treatment of decompensated liver *** of stem cells has offered a new dimension for regenerative therapy and has been considered as one of the potential adjuvant treatment modality in patients with end stage liver diseases(ESLD). Human fetal hepatic progenitor cells are less immunogenic than adult ones. They are highly propagative and challenging to cryopreservation. In our earlier studies we have demonstrated that fetuses at 10-18 wk of gestation age contain a large number of actively dividing hepatic stem and progenitor cells which possess bipotent nature having potential to differentiate into bile duct cells and mature hepatocytes. Hepatic stem cell therapy for the treatment of ESLD is in their early stage of the translation. The emerging technology of decellularization and recellularization might offer a significant platform for developing bioengineered personalized livers to come over the scarcity of desired number of donor organs for the treatment of ESLD. Despite these significant advancements long-term tracking of stem cells in human is the most important subject nowadays in order to answer several unsettles issues regarding the route of delivery, the choice of stem cell type(s), the cell number and the timepoint of cell delivery for the treatment in a chronic setting. Answering to these questions will further contribute to the development of safer, noninvasive, and repeatable imaging modalities that could discover better cell therapeutic approaches from bench to bedside. Combinatorial approach of decellularization and nanotechnology could pave a way towards the better understanding in determination of cell fate posttransplantation.

关键词： Hepatic stem cells Bioengineering Livercirrhosis Labeling and tracking

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Bioengineered humanized livers as better three-dimensional drug testing model system

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World Journal of Hepatology 2018年第1期10卷 22-33页

作者： sandeep kumar vishwakarma Avinash Bardia Chandrakala Lakkireddy Raju Nagarapu Md Aejaz Habeeb Aleem Ahmed Khan Central Laboratory for Stem Cell Research and Translational Medicine Centre for Liver Research and Diagnostics Deccan College of Medical Sciences

AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity *** The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological *** The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.

关键词： Acellularization Repopulation Drug testing Humanized liver Bioengineering

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Long-term and non-invasive in vivo tracking of DiD dye-labeled human hepatic progenitors in chronic liver disease models

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World Journal of Hepatology 2022年第10期14卷 1884-1898页

作者： Chaturvedula Tripura Srinivas Gunda sandeep kumar vishwakarma Avinash Raj Thatipalli Jedy Jose Mahesh kumar Jerald Aleem Ahmed Khan Gopal Pande Cell and Stem Cell Biology CSIR-Centre for Cellular and Molecular BiologyHyderabad 500007TelanganaIndia Central Laboratory for Stem Cell Research and Translational Medicine Centre for Liver Research and DiagnosticsDeccan College of Medical SciencesHyderabad 500058TelanganaIndia

BACKGROUND Chronic liver diseases(CLD)are the major public health burden due to the continuous increasing rate of global morbidity and *** inherent limitations of organ transplantation have led to the development of stem cell-based therapy as a supportive and promising therapeutic ***,identifying the fate of transplanted cells in vivo represents a crucial *** To evaluate the potential applicability of DiD dye as a cell labeling agent for longterm,and non-invasive in vivo tracking of transplanted cells in the *** Magnetically sorted,epithelial cell adhesion molecule positive(1×106 cells/mL)fetal hepatic progenitor cells were labeled with DiD dye and transplanted into the livers of CLD-severe combined immunodeficiency(SCID)***-infrared(NIR)imaging was performed for in vivo tracking of the DiD-labeled transplanted cells along with colocalization of hepatic markers for up to 80 *** existence of human cells within mouse livers was identified using Alu polymerase chain reaction and *** NIR fluorescence imaging of CLD-SCID mice showed a positive fluorescence signal of DiD at days 7,15,30,45,60,and 80 ***,positive staining of cytokeratin,c-Met,and albumin colocalizing with DiD fluorescence clearly demonstrated that the fluorescent signal of hepatic markers emerged from the DiD-labeled transplanted *** of liver function was also observed with serum levels of glutamic-oxaloacetic transaminase,glutamate-pyruvate transaminase,and *** detection of human-specific Alu sequence from the transplanted mouse livers provided evidence for the survival of transplanted cells at day *** DiD-labeling is promising for long-term and non-invasive in vivo cell tracking,and understanding the regenerative mechanisms incurred by the transplanted cells.

关键词： Chronic liver diseases Cell transplantation Cell tracking and imaging DiD Hepatic progenitors

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Bioengineered functional humanized livers： An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases

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World Journal of Hepatology 2018年第11期10卷 822-836页

作者： sandeep kumar vishwakarma Chandrakala Lakkireddy Avinash Bardia Syed Ameer Basha Paspala Chaturvedula Tripura Md Aejaz Habeeb Aleem Ahmed Khan Central Laboratory for Stem Cell Research and Translational Medicine Centre for Liver Research and Diagnostics Deccan College of Medical Sciences Kanchanbagh Hyderabad 500058 Telangana India Dr Habeebullah Life Sciences Attapur Hyderabad 500058 Telangana India CSIR-Centre for Cellular and Molecular Biology Habsiguda Hyderabad 500007 Telangana India

End stage liver diseases （ESLD） represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss t

关键词： Bioengineered liver Omentum Secondary organ Transplantation End stage liver diseases

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Cell-free mitochondrial DNA quantification in ischemic stroke patients for non-invasive and real-time monitoring of disease status

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World Journal of Translational Medicine 2022年第2期10卷 14-28页

作者： Nusrath Fathima Sandhya Manorenj sandeep kumar vishwakarma Aleem Ahmed Khan Central Laboratory for Stem Cell Research and Translational Medicine Centre for Liver Research and DiagnosticsDeccan College of Medical SciencesHyderabad 500058TelanganaIndia Department of Neurology Princess Esra HospitalDeccan College of Medical SciencesHyderabad 500058TelanganaIndia

BACKGROUND Acute ischemic stroke(AIS)is one of the major causes of the continuous increasing rate of global mortality due to the lack of timely diagnosis,prognosis,and *** study provides a primitive platform for non-invasive and cost-effective diagnosis and prognosis of patients with AIS using circulating cellfree mitochondrial DNA(cf-mtDNA)quantification and *** To evaluate the role of cf-mtDNA as s non-invasive,and affordable tool for realtime monitoring and prognosticating AIS patients at disease onset and during *** This study enrolled 88 participants including 44 patients with AIS and 44 healthy controls with almost similar mean age group at stroke onset,and at 24 h and 72 h of *** blood samples were collected from each study participant and plasma was separated using *** cf-mtDNA concentration was quantified using nanodrop reading and validated through real-time quantitative polymerase chain reaction(RT-qPCR)of NADH-ubiquinone oxidoreductase chain 1(ND1)relative transcript expression *** Comparative analysis of cf-mtDNA concentration in patients at disease onset showed significantly increased levels compared to control individuals for both nanodrop reading,as well as ND1 relative expression levels(P<0.0001).Intergroup analysis of cf-mtDNA concentration using nanodrop showed significantly reduced levels in patients at 72 h of treatment compared to onset(P<0.01).However,RT-qPCR analysis showed a significant reduction at 24 h and 72 h of treatment compared to the disease onset(P<0.001).The sensitivity and specificity were relatively higher for RT-qPCR than nanodrop-based cfmtDNA *** analysis of both cf-mtDNA concentration as well as ND1 relative expression with National Institute of Health Stroke Scale score at baseline showed a positive *** In summary,quantitative estimation of highly pure cf-mtDNA provides a simple,highly sensitive and specific,no

关键词： Cell-free mitochondrial DNA NADH-ubiquinone oxidoreductase chain 1 Ischemic stroke Circulating biomarker National Institute of Health Stroke Scale score Stroke assessment Severity and outcome

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Role of cell-free DNA for predicting incidence and outcome of patients with ischemic stroke

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World Journal of Neurology 2022年第1期8卷 1-9页

Early diagnosis and prognosis of ischemic stroke remains a critical challenge in clinical settings.A blood biomarker can be a promising quantitative tool to represent the clinical manifestations in ischemic ***-free DNA(cfDNA)has recently turned out to be a popular circulating biomarker due to its potential relevance for diagnostic applications in a variety of *** bright outlook of cfDNA in clinical applications,very less is known about its origin,composition,or *** recent studies have identified cell-derived mitochondrial components including mitochondrial DNA(mtDNA)in the extracellular spaces including blood and cerebrospinal ***,the time course of alterations in plasma mtDNA concentrations in patients after an ischemic stroke is poorly *** is thought to be freed into the plasma shortly after the commencement of an ischemic stroke and then gradually ***,the importance of cell-free mtDNA(cf-mtDNA)in ischemic stroke is still *** review summarizes about the utility of biomarkers which has been standardized in clinical settings and role of cfDNA including cfmtDNA as a non-invasive potential biomarker of ischemic stroke.

关键词： Ischemic stroke Mitochondria Circulating cell-free DNA Plasma nucleic acid Mortality

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Current progress and emerging technologies for generating extrapancreatic functional insulin-producing cells

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World Journal of Translational Medicine 2022年第1期10卷 1-13页

作者： Md Aejaz Habeeb sandeep kumar vishwakarma Safwaan Habeeb Aleem Ahmed Khan Centre for Liver Research and Diagnostics Deccan College of Medical SciencesHyderabad 500058TelanganaIndia

Diabetes has been one of the major concerns in recent years,due to the increasing rate of morbidity and mortality *** available treatment strategies for uncontrolled diabetes mellitus(DM)are pancreas or islet ***,these strategies are limited due to unavailability of quality pancreas/islet donors,life-long need of immunosuppression,and associated *** therapy has emerged as a promising alternative options to achieve the clinical benefits in the management of uncontrolled *** the last few years,various sources of cells have been used to convert into insulin-producingβ-like *** extrapancreatic sources of cells may play a significant role inβ-cell turnover and insulin secretion in response to environmental ***/progenitor cells from liver have been proposed as an alternative choice that respond well to glucose stimuli under strong transcriptional *** liver is one of the largest organs in the human body and has a common endodermal origin with pancreatic ***,liver has been proposed as a source of a large number of insulinproducing *** merging of nanotechnology and 3D tissue bioengineering has opened a new direction for producing islet-like cells suitable for in vivo transplantation in a cordial *** review summarizes extrapancreatic sources for insulin-secreting cells with reference to emerging technologies to fulfill the future clinical need.

关键词： Diabetes mellitus Cell-based therapy Insulin producing cells Extrapancreatic sources Biomaterials Tissue engineering

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Linear and nonlinear propagation characteristics of multi-Gaussian laser beams

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Chinese Physics B 2020年第11期29卷 370-379页

作者： Naveen Gupta sandeep kumar Lovely Professional University PhagwaraIndia

Theoretical investigation on the propagation characteristics of a new class of laser beams known as multi Gaussian(M.G)laser beams has been *** investigate the linear characteristics,propagation of the laser beam in vacuum has been ***,the nonlinear characteristics have been investigated in *** nonlinearity of the plasma has been modeled by relativistic mass nonlinearity of the plasma electrons in the field of laser *** is based on finding the semi analytical solution of the wave equation for the slowly varying envelope of the laser ***,the dynamical evolutions of the beam width and longitudinal phase of the laser beam have been investigated in detail.

关键词： self-focusing multi Gaussian self phase modulation self-channeling

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Piecewise linear programming approach to solve multi-objective matrix games with I-fuzzy goals

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Journal of Control and Decision 2021年第1期8卷 1-13页

作者： sandeep kumar Department of Mathematics Ch.Charan Singh UniversityMeerut 250004Uttar PradeshIndia

The intuitionistic fuzzy set(I-fuzzy set)plays an effective role in game theory when players face‘neither this nor that’situation to set their *** study presents a maxmin–minmax solution to multi-objective two person zero-sum matrix games with I-fuzzy *** this article,a class of piecewise linear membership and non-membership functions for I-fuzzy goals is *** functions are more effective in real games because marginal rate of increase(decrease)of such membership functions(non-membership functions)is different in different intervals of tolerance ***,one numerical example is given to examine the effectiveness and advantages of the proposed results.

关键词： Intuitionistic fuzzy set multi-objective matrix game I-fuzzy goals maxmin-minmax solution piecewise linear function

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Molecules against COVID-19:An in Silico Approach for Drug Development

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Journal of Electronic Science and Technology 2021年第1期19卷 14-24页

作者： Rhythm Bharti sandeep kumar Shukla the Sri Venkateswara College University of DelhiNew Delhi 110021. The Institute of Nuclear Medicine and Allied Sciences Defence Research and Development OrganizationDelhi 110054

A large number of deaths have been caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)worldwide,turning it into a serious and momentous threat to public *** study tends to contribute to the development of effective treatment strategies through a computational approach,investigating the mechanisms in relation to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid(RNA)-dependent RNA polymerase(RdRp).Molecular docking was performed to screen six naturally occurring molecules with antineoplastic properties(Ellipticine,Ecteinascidin,Homoharringtonine,Dolastatin 10,Halichondrin,and Plicamycin).Absorption,distribution,metabolism,and excretion(ADME)investigation was also conducted to analyze the druglike properties of these *** docked results have clearly shown binding of ligands to the SARS-CoV-2 RdRp ***,all ligands were found to obey Lipinski’s rule of *** results provide a basis for repurposing and using molecules,derived from plants and animals,as a potential treatment for the coronavirus disease 2019(COVID-19)infection as they could be effective therapeutics for the same.

关键词： Coronavirus disease 2019(COVID-19) drug repurposing,molecular docking natural therapeutics RNA-dependent RNA polymerase(RdRp) severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

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