Presenter: Teresa Holm

Transcription

1 Slides are from Level 3 Biology Course Content Day, 7 th November 2012 Presenter: Teresa Holm Teachers are free to use these for teaching purposes with appropriate acknowledgement

2 Human Stem cells Dr Teresa Holm Department of Molecular Medicine & Pathology School of Medical Sciences University of Auckland

3 What are stem cells and why are they important? Potential to develop into many different cell types in the body Repair/replacement of lost tissues (skin, gut, blood) Unspecialized cells ( primitive ) capable of self-renewal by cell division Can be induced to become tissue-specific mature cells with special functions. Self renewal Stem cell Mature cells

4 The promise of stem cells Tissue engineering Cell based therapies Disease in a dish

5 Types of Human Stem Cells Adult stem cells naturally found in some of our organs Embryonic stem cells- derived from embryos Induced pluripotent stem (ips) cells generated from any cell

6 Adult Stem Cells Blood Brain Gut Muscle Skin Mesenchymal stem cells Not all organs have stem cells

7 Mesenchymal Stem Cells Muscle Cartilage Bone Fat Traditionally found in the bone marrow but can be isolated from many tissues. Can turn into adipocytes, cartilage, bone, tendons, muscle, and skin. Release anti-inflammatory and immunomodulatory factors

8 Blood stem cells Self renewal Blood Stem cell Rapid turnover: 2.5 million red blood cells made/destroyed per second Mature blood cells Gut stem cells Rapid turnover: 2-3 days

9 In widespread clinical use: Adult stem cell therapies Blood stem cell transplants - Bone marrow (1968) - Peripheral blood (1986) - Umbilical cord (1988) Tissue- type matching important blood banks Other cell therapies that involve stem cells as part of the Issue transplanted: Skin graps Involve skin stem cells in the grap Corneal transplants Corneal stem cells

10 Types of Human Stem Cells Adult stem cells naturally found in some of our organs Embryonic stem cells- derived from embryos Induced pluripotent stem (ips) cells generated from any cell

11 Embryos and Embryonic stem cells Sperm Embryos Egg 5 days old Not restricted in their lineage potenial Embryonic stem cells (ES cells) Human ES cells derived 1998 Pancreas Blood Muscle Brain Liver

12 ES cells can be dangerous: ES cells Teratoma (tumour) Pancreas Blood Muscle Brain Liver Purity important And there are ethical concerns:

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14 New Zealand s posiion Research with established human ES cell lines is allowed with ethics commisee approval. The crea,on of new ES cell lines in NZ is covered by the scope of The Human Assisted ReproducWve Technology (HART) Act with guidelines recommended by the Advisory CommiSee on Assisted ReproducWve Technology (ACART). A decision is pending from the Minister of Health.

15 ES cell therapies Cell based therapies Mature Purify Transplant FDA approval to test ES- derived rewnal pigment epithelial cells for the treatment of two types of blindness

16 Other applications of ES (and ips) cells Bioartificial organs: Liver Kidney Pancreatic islets Limitless source of mature human cell types Drug toxicity screening Kidney (19% of drugs in preclinical trials fail due to renal toxicity) Liver Heart

17 Types of Human Stem Cells Adult stem cells naturally found in some of our organs Embryonic stem cells- derived from embryos Induced pluripotent stem (ips) cells generated from any cell

18 ES cells Embryo ES cell Mature PaIent Induced pluripotent stem (ips) cells Special factors Reprogramming ips cell Mature

19 World s most famous sheep Roslin InsWtute, Edinburgh (1996) Prof Ian Wilmut Dolly taught us that mature cells of the body can be returned to an embryonic state = reprogramming 1996

20 The cloning of Dolly Mature adult cell GeneWcally idenwcal Udder cell Re- programmed cell

21 Cloning = somaic cell nuclear transfer Not supported by scienists DNA ReproducWve cloning Baby Egg Embryo TherapeuWc cloning ES cells Supported by scienists

22 Reprogramming Imeline Dr Shinya Yamanaka Dr John Gurdon factors Mature cell (eg skin, blood) Embryonic stem cell- like (ips cell)

23 The Nobel Prize in Physiology and Medicine 2012 For the discovery that mature cells can be reprogrammed to become pluripotent John B. Gurdon and Shinya Yamanaka

24 Cell based therapies for ips cells PaWent eg sickle cell anaemia Coax ips cells into blood stem cells Personalized ips cells Correct genewc defect Return to pawent (no rejecwon)

25 Proof- of- principle in the mouse ips Corrected ips cells HematopoieWc stem cells Sickle cell anaemia (genewc defect) Teratoma Neurons Parkinson s disease

26 Direct reprogramming/conversion Yamanaka factors Skin cell ips cell Neuron factors Skin cell Neuron Heart muscle Blood

27 Future challenge: Spot the difference Embryonic Stem Cells Induced Pluripotent Stem Cells

28 Summary Adult stem cells Occur naturally in the body Restricted potentials (eg blood stem cells make blood) Immune rejection is an issue Clinical Bone marrow transplant. MSCs (experimental) Human embryonic stem cells Derived from embryos (ethical issues) Unrestricted potential (can make all cell types in the body) Safety issues (risk of teratoma) Immune rejection is an issue ACT retina (experimental) ips cells Derived from any cell (no ethical issues) Unrestricted potential (can make all cell types in the body) Safety issues (risk of teratoma) Immune rejection is not (as much of) an issue Value as a drug screening tool (Disease in a dish) None yet

29 The promise of stem cells. Tissue engineering SWll a long way off for most organs Disease in dish Reality now BeSer understanding of diseases Drug screening Cell based therapies Immune response Safety (teratoma, stability, quality)