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Regulating the fate of stem cells for regenerating the intervertebral disc degeneration

World Journal of Stem Cells 2021年第12期13卷 1881-1904页

作者： Sobia Ekram shumaila khalid Asmat Salim Irfan Khan Dr.Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan

Lower back pain is a leading cause of disability and is one of the reasons for the substantial socioeconomic *** etiology of intervertebral disc(IVD)degeneration is complicated,and its mechanism is still not completely *** such as aging,systemic inflammation,biochemical mediators,toxic environmental factors,physical injuries,and genetic factors are involved in the progression of its ***,no therapy for restoring degenerated IVD is available except pain management,reduced physical activities,and surgical ***,it is imperative to establish regenerative medicine-based approaches to heal and repair the injured disc,repopulate the cell types to retain water content,synthesize extracellular matrix,and strengthen the disc to restore normal spine *** therapy has gained attention for IVD management as an alternative therapeutic *** this review,we present an overview of the anatomical and molecular structure and the surrounding pathophysiology of the *** therapeutic approaches,including proteins and growth factors,cellular and gene therapy,and cell fate regulators are ***,small molecules that modulate the fate of stem cells for their differentiation into chondrocytes and notochordal cell types are highlighted.

关键词： Stem cell Intervertebral disc Degeneration Inflammation Cell therapy Gene modification

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Transcription regulators differentiate mesenchymal stem cells into chondroprogenitors,and their in vivo implantation regenerated the intervertebral disc degeneration

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World Journal of Stem Cells 2022年第2期14卷 163-182页

作者： shumaila khalid Sobia Ekram Asmat Salim G.Rasul Chaudhry Irfan Khan Dr.Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan Department of Biological Sciences Oakland UniversityRochesterMI 48309United States

BACKGROUND Intervertebral disc degeneration(IVDD)is the leading cause of lower back *** degeneration is characterized by reduced cellularity and decreased production of extracellular matrix(ECM).Mesenchymal stem cells(MSCs)have been envisioned as a promising treatment for degenerative ***-based therapy using ECM-producing chondrogenic derivatives of MSCs has the potential to restore the functionality of the intervertebral disc(IVD).AIM To investigate the potential of chondrogenic transcription factors to promote differentiation of human umbilical cord MSCs into chondrocytes,and to assess their therapeutic potential in IVD *** MSCs were isolated and characterized morphologically and immunologically by the expression of specific *** were then transfected with Sox-9 and Six-1 transcription factors to direct differentiation and were assessed for chondrogenic lineage based on the expression of specific *** differentiated MSCs were implanted in the rat model of *** regenerative potential of transplanted cells was investigated using histochemical and molecular analyses of *** Isolated cells showed fibroblast-like morphology and expressed CD105,CD90,CD73,CD29,and Vimentin but not CD45 *** of Sox-9 and Six-1 greatly enhanced the gene expression of transforming growth factor beta-1 gene,BMP,Sox-9,Six-1,and Aggrecan,and protein expression of Sox-9 and *** implanted cells integrated,survived,and homed in the degenerated intervertebral *** grading showed that the transfected MSCs regenerated the IVD and restored normal *** Genetically modified MSCs accelerate cartilage regeneration,providing a unique opportunity and impetus for stem cell-based therapeutic approach for degenerative disc diseases.

关键词： Intervertebral disc degeneration Human umbilical cord Transcription factors Mesenchymal stem cells Gene expression Regeneration

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Zinc enhances the cell adhesion,migration,and self-renewal potential of human umbilical cord derived mesenchymal stem cells

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World Journal of Stem Cells 2023年第7期15卷 751-767页

作者： Iqra Sahibdad shumaila khalid G Rasul Chaudhry Asmat Salim Sumreen Begum Irfan Khan Dr.Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan Department of Biological Sciences Oakland UniversityRochesterMI 48309United States Stem Cell Research Laboratory(SCRL) Sindh Institute of Urology and Transplantation(SIUT)Karachi 74200SindhPakistan

BACKGROUND Zinc(Zn)is the second most abundant trace element after Fe,present in the human *** is frequently reported in association with cell growth and proliferation,and its deficiency is considered to be a major disease contributing *** To determine the effect of Zn on in vitro growth and proliferation of human umbilical cord(hUC)-derived mesenchymal stem cells(MSCs).METHODS hUC-MSCs were isolated from human umbilical cord tissue and characterized based on immunocytochemistry,immunophenotyping,and tri-lineage *** impact of Zn on cytotoxicity and proliferation was determined by MTT and Alamar blue *** determine the effect of Zn on population doubling time(PDT),hUC-MSCs were cultured in media with and without Zn for several *** in vitro scratch assay was performed to analyze the effect of Zn on the wound healing and migration capability of hUC-MSCs.A cell adhesion assay was used to test the surface adhesiveness of *** analysis of genes involved in the cell cycle,proliferation,migration,and selfrenewal of hUC-MSCs was performed by quantitative real-time polymerase chain *** protein expression of Lin28,a pluripotency marker,was analyzed by *** Zn at lower concentrations enhanced the rate of proliferation but at higher concentrations(>100μM),showed concentration dependent cytotoxicity in ***-MSCs treated with Zn exhibited a significantly greater healing and migration rate compared to untreated *** also increased the cell adhesion rate,and colony forming efficiency(CFE).In addition,Zn upregulated the expression of genes involved in the cell cycle(CDC20,CDK1,CCNA2,CDCA2),proliferation(transforming growth factorβ1,GDF5,hypoxia-inducible factor 1α),migration(CXCR4,VCAM1,VEGF-A),and self-renewal(OCT4,SOX2,NANOG)of *** of Lin28 protein was significantly increased in cells treated with *** Our findings suggest that zinc enhances the proliferat

关键词： Human umbilical cord Mesenchymal stem cells Zinc Cell proliferation In vitro expansion

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