Stem cells in regenerative medicine ,Mechanism and signalling pathways

Stem cells in regenerative medicine Mechanism and signalling pathways

1. . STEM CELLS IN REGENERATIVE MEDICINE , MECHANISM AND SIGNALLING PATHWAYS . Prepared by : Nighat Jan Enrollment number : 2016cukmr28 Submitted to : DR.OWAIS BHAT SCIENTIST D

2. Introduction Types of stem cells Induced pluripotent stem cells ( IPSC ) Signalling pathways Types of pathways Conclusion Contents

3. Introduction Stem cells are cells with ability of self renewal and are potent and give rise to many differentiated cells Stem cell can be totipotent, pluripotent, multipotent or unipotent based on its potential Factors responsible for pluripotency of cells are specific transcriptional factors. (oct4, nanog,sox2 etc ) Gilbert (developmental biology edition 11).

4. Regenerative medicine Functional restoration of tissue or organs With the help of stem cell technology is regenerative medicine Therapeutic possibilities of embryonic stem cells (ESCs) lie in their ability to differentiate into any cell type For successful regenerative outcomes, transplanted stem cells must survive, proliferate, and differentiate in site specific manner https://search.app.goo.gl/qnuZ3G1

5. Types of stem cell used in regenerative medicine ESC(embryonic stem) MSCs(mesenchymal stem cells) BMSc ( bone marrow stem cells) UCSc (umbilical cord stem cells) IPSCs(Induced pluripotent stem cells)

6. Embryonic stem cell These cells can be differentiated into around 200 types of cells These cells are derived from inner cell mass of blastocyst . J.J.thomsan first isolated ESC and cultured the cells. ESCs is governed by functional dynamics of transcription factors OCT4 , SOX2 , NANOG , and so forth, which are termed as pluripotency factors. https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=4969512_IJCB2016-6940283.002.jpg

7. Age-related macular degeneration (ARMD). The genomic incorporation of COCO gene causes suppression of TGFβ , BMP , and Wnt signalling pathways Regeneration of cardiac tissue can be achieved by transplantation of cardiomyocyte via ESCs-derived cardiovascular progenitors ESCs derived liver stem cells can be transformed into Cytp450-hepatocytes, mediating chemical modification and catabolism of toxic xenobiotic drugs However there are ethical concern that are to be taken care of which proves to a major limitation in the process and also HLA typing in carried out so there are chances of rejection

8. Regenerative medicine in case of liver disease Since liver is most active organ in body carrying out detoxification and other processes in which cells are degraded and can cause liver failure Mesenchymal stem cells can be used to generate hepatocytes and and tackle the problem These are fibroblast like cells present inside bone marrow or adipocytes also don’t show immunogenic properties AT-MSC are taken via liposuction or plastic surgery.

9. In- vitro hepatic differentiation EGF FGF HGF(hepatocytes growth factor) NTA(nicotine amide) ITS(insulin transferrin selenium) OSM( oncostatin M) DEX (dexamethasone)

10. IPSCs In 2006 kazutoshi Takahashi and shinya yamanaka introduced four genes that encoded transcriptional factors in adult fibroblast mouse cell and cell showed properties of ESC SOX-2 and OCT-4( activate nanog that established pluripotency and blocked differentiation) c- Myc (opened up chromatin and made genes accessible to sox-2 ,oct-4 and nanog ) Klf4 ( prevent cell death)

11. 24 genes were selected for transfer initially Gene was inserted at Fbx15 locus which is responsible for embryonic development Transfer was screened by G418 antibiotic Finally four genes were found to be responsible These cells formed teratocarcinoma on injecting to a mice Cells were indentified in mice on injecting in blastocyst of mice https://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/14465358/f1_rossant_448260a-f1.2.jpg?hl=en_GB

12. TIMELINE

13. Signalling pathways . Pluripotency at molecular level is mediated by TGF BETA which signals through SMAD2/3 and FGFR which activate MaPK and AKT pathway Wnt signalling also plays the role via beta catenin Activate pluripotency factors ,which in turn activate genes specific to stem cells Some other stem cell markers are SSEA3-4,TRA 1-60,TRA1-81 BNP4 pathway via SMAD1-5 and 8 promotes differentiation

14. How stem cells reach injured site Mainly regulated by autonomous nervous system Niche of stem cell are mainly maintained by norepinephrine which reduces SDF1 expression and HSC are released into blood circulation SDF( stromal derived factor -1) cxcr4 and cxcr7 are receptor responsible for down regulation of caspase 3 pathway Also increase in BCL2/BAC ratio stops cell apoptosis

15. Wnt signalling pathway Gilbert developmental biology edition 11

16. Gilbert developmental biology edition 11 TGF-BETA PATHWAY

17. https://search.app.goo.gl/XLtm16x AKT PATHWAY

18. Refrence Development biology by Gilbert 11 edition Stem cell bio by leinzt 3 rd edition www.pubmed.com / stemcells and regenerative medicine. Stem cell-based therapy for human diseases review article by DUC M. Hoang T, Phuong T(2022) www.nature.com / stem cell therapy and signalling therapy Afshari et al. Stem Cell Research & Therapy (2020)https://doi.org/10.1186/s13287-020-1555-8 THANK YOU.