1. Stem Cell therapy: Status and Ethics ARIJIT BHATTACHARJEE WORKSHOP ONEMERGING AREAS OF MOLECULAR BIOLOGY AND IMMUNOLOGY, 21ST MAY- 26TH MAY , 2012,.KARIMGANJ COLLEGE , KARIMGANJ, ASSAM.
2. Stem celldifferentiate (develop)A cell that has the ability to continuously divide andinto various other kind(s) of cells/tissues . In mammals there are two broadkinds of stem cells: Embryonic stem cells and Adult stem cells. The stemcells and progenitor cells acts as a repair system for the body replenishingadult tissues. Stem cell Stem cell SELF-RENEWAL DIFFERENTIATION (copying) (specializing) Identical stem cells Specialized cells
3. Comparison of Embryonic and Adult stem cells Embryonic stem cell Adult stem cellsDerived from the inner cell mass They produce cells specific to the tissue in which they are found.Pluripotent They are relatively unspecializedCan develop into more than 200different cells However they are predetermined to give rise to specific cell types whenDifferentiate into cells of the 3 they differentiategerm cell layers e.g: haematopoietic, bone marrow, neuralBecause of their capacity ofunlimited expansion andpluripotency – useful inregenerative medicine
4. Stem Cell Properties:Self renewal - the ability to go through numerous cycles of cell division whilemaintaining the undifferentiated state.Potency – the capacity to differentiate into specialized cell types.Totipotent stem cells -cells produced by the first few divisions of the cell . So canform any cell of the embryo as well as the placenta.Pluripotent – these cells differentiate into cells derived from the three germ celllayers. e. g. haematopoietic stem cells, neural and mesenchymal stem cells.Multipotent – these cells can produce cells of a closely related family of cells. e.g.:haematopoietic stem cells, neural and mesenchymal stem cells.Unipotent – these cells only produce one cell type., but have the property of selfrenewal which distinguishes them from the non stem cells.
5. Why self-renew AND differentiate? 1 stem cell 1 stem cell 4 specialized cellsSelf renewal - maintains the Differentiation - replaces dead or damagedstem cell pool cells throughout your life
6. Kinds of Stem Cells/ stem cell jargon Stem cell type Description Examples Each cell can develop into a Cells from early (1-3Totipotent new individual days) embryos Some cells of Cells can form any (over 200)Pluripotent blastocyst (5 to 14 cell types days) Fetal tissue, cord Cells differentiated, but canMultipotent blood, and adult stem form a number of other tissues cells
7. Stem Cell Differentiation
8. TYPES OF STEM CELLS: EMBRYONIC STEM CELL:FOUND IN INNER LAYER OF BLASTOCYST- Differentiates into specialized cells. TISSUE STEM CELL: FOUND IN DIFFERENT TISSUES LIKE BONE MARROW, MUSCLE, ETC. Differentiates into various specialized cell types like blood cells. INDUCED PLURIPOTENT(iPS) STEM CELLS: Adult cells which genetically reprogrammed to add certain genes, they behave like embryonic stem cell and differentiate into specialized cells. ADVANTAGES OF iPS CELLS: No Need for Embryos!!!!!!!!!!!
9. WORKSHOP ON EMERGING AREAS ONMOLECULAR BIOLOGY AND IMMUNOLOGY,MAY 21-MAY 26, 2012, KARIMGANJ COLLEGE , KARIMGANJ
10. WORKSHOP ON EMERGING AREAS ONMOLECULAR BIOLOGY AND IMMUNOLOGY,MAY 21-MAY 26, 2012, KARIMGANJ COLLEGE , KARIMGANJ
11. Where are stem cells found? embryonic stem cells tissue stem cellsblastocyst - a very early embryo fetus, baby and throughout life
12. Stem cell nichesNiche stem cellMicroenvironment around stem cells that provides supportand signals regulating self-renewal and differentiation niche Direct contact Soluble factors Intermediate cell
13. Tens of thousands of frozenembryos are routinelydestroyed when couples finishtheir treatment. These surplus embryos canbe used to produce stem cells. Regenerative medicalresearch aims to develop thesecells into new, healthy tissueto heal severe illnesses.
14. Tissue stem cells: Principles of renewing tissues Stem cell stem cell: - self renew- divide rarely committed progenitors:- high potency - “transient amplifying cells” specialized cells: - rare - multipotent - work - divide rapidly - no division - no self-renewalEXAMPLES OF SUCH STEM CELL INCLUDE HSCs, NSCs AND GSCs, etc.
15. Tissue stem cells:Haematopoietic stem cells (HSCs) NK cell T cell B cell dendritic cell megakaryocyte platelets HSC erythrocytes macrophage neutrophil bone marrow eosinophil basophil specialized cells committed progenitors
18. Tissue stem cells:Mesenchymal stem cells (MSCs) Bone (osteoblasts) MSC Cartilage (chondrocytes) bone marrow Fat (adipocytes) committed progenitors specialized cells
19. APPLICATIONS OF STEM CELL IN BIOMEDICAL RESEARCH AND REGENERATIVE MEDICINE
20. Derivation and Use of Embryonic Stem CellLines Isolate inner cell mass Outer cells (destroys embryo) (forms placenta) Inner cells (forms fetus) Culture cells Day 5-6 Blastocyst “Special sauce” Liver Heart repaired Kidney Heart muscle
21. Somatic Cell Nuclear Transfer The nucleus of a donatedegg is removed and replacedwith the nucleus of a mature,"somatic cell" (a skin cell, forexample). No sperm is involved in thisprocess, and no embryo iscreated to be implanted in awoman’s womb. The resulting stem cells canpotentially develop intospecialized cells that are usefulfor treating severe illnesses.
22. SCNT CONT… WORKSHOP ON EMERGING AREAS ON MOLECULAR BIOLOGY AND IMMUNOLOGY,MAY 21- MAY 26, 2012, KARIMGANJ COLLEGE , KARIMGANJ
23. Stem Cell Cultivation
25. Possible Uses of Stem CellTherapy Replaceable tissues/organs Repair of defective cell types Delivery of genetic therapies Delivery chemotherapeutic agentsIn theory, stem cell technology could be used to produce replaceable tissues or organs.Defective tissues/organs could be repaired using healthy cells. It would also be possible togenetically engineer stem cells to accomplish activities that they would not ordinarily beprogrammed to do. Part of this engineering could involve the delivery of chemotherapeuticagents for treatment of cancers and tumors.
26. Potential application of fetal stem cells Inthe field of fetal medicine: Non invasive prenatal diagnosis Intrauterine stem cell transplantation Gene therapyTherapeutic applications of embryonic stemcells –ES cell The potential to form 200 or more cells. Hence used in regenerative medicine in cases like cardiac failure, Parkinsons disease, diabetes. These cells are being coaxed to differentiate into cardiomyocytes, neural stem cells, insulin producing cell and even germ cells.
27. Induced Pluripotent Stem (iPS) cell in Regenerativemedicine Fig.
28. Blood is collected from umbilical cord immediately after delivery about 100- 150cc The number of cells in 1 ml is 40,000 They are stored in blood banks at -196deg celsius in a state of suspended animation and restart their activity on thawing.
29. Advantages over bone marrow cells1. High rate of engraftment2. More tolerant to tissue matches3. Less severe GVHD4. Rarely contaminated with latent virus5. Easy to collect, not painful6. Superior proliferative capacity7. Greater immunological naievity8. Unlimited supply9. Lower cost
30. Ailments for which stem cellsare being used now Acute leukemias Chronic leukemias Myelodysplastic syndromes Marrow failure Myeloproliferative disorders Lymphoproliferati ve disorders
31. Phagocyte disorders Inherited disorders like Lesch Nyhan syndrome, beta Thallesemia etc Inherited platelet abnormalities Inherited metabolic disorders like Mucopolysaccharidosis, Hurler’s syndrome, Krabbe disease, Niemann- pick disease etc. Histocytic disorders Inherited erythrocyte abnormalities Inherited immune system disorders like ataxia telangectesia, DiGeorge syndrome, SCID etc Plasma cell disorder Malignancies like neuroblastoma, Ewing sarcoma, Renal cell CA etc
33. The Ethical DebateIn favor of ESCR: Embryonic stem cell research (ESCR) fulfills the ethical obligation to alleviate human suffering. Since excess IVF embryos will be discarded anyway, isn’t it better that they be used in valuable research? SCNT (Therapeutic Cloning) produces cells in a Petri dish, not a pregnancy.Against ESCR: In ESCR, stem cells are taken from a human blastocyst, which is then destroyed. This amounts to “murder.” There is a risk of commercial exploitation of the human participants in ESCR. Slippery slope argument: ESCR will lead to reproductive cloning.
34. Key Ethical Issues The blastocyst used in stem cell research is microscopically small and has no nervous system. Does it count as a “person” who has a right to life? What do various religions say about when personhood begins? Does science have a view on this? In a society where citizens hold diverse religious views, how can we democratically make humane public policy?
35. Guidelines for stem cell research in India Compulsory registration of the existing cell lines to be registered under specific apex bodies in the field Genetic research dealing with human egg or sperm and genetic engineering and then transfer of human blastocysts will not be allowed Research and therapy using fetal/placental stem cell will be allowed Termination of pregnancy cannot be sought for donating fetal tissue for therapeutic or financial benefits All the umbilical cord blood banks should be registered with Drug Controller General of India Research into human cloning is not to be done These guidelines are aimed to encourage development of sound research and therapy, prevent any misuse of human embryos and fetuses and protect patients from fraudulent treatments in the name of stem cell research.