The stem cell century

1. The stem cell century Dr.Saranya Nandakumar Medical Director Asia CRYO CELL Pvt Ltd http://www.lifecellindia.com

2. Chief sources of stem cells

3. Other sources Almost all the organs in the body in small quantities Fat – one of the richest sources ( 150 ccs - 4 million cells) OEC – Olfactory Ensheathing Cells Teeth – Milk teeth and wisdom teeth Cord lining Amnion

4. Why is this cell so special ? Plasticity or ability to differentiate Ability to divide continuously Immunological immaturity

5. The Stem cell controversy

6. The non controversial sources Bone Marrow Qty of harvest larger Engraftment faster GVHR 75% Contamination more Tedious collection Longer time to find donors HLA typing –5/6 or 6/6 Cord blood Harvest quantum less Engraftment takes longer GVHR 38% Less contamination Simple collection Donor search time –halved HLA match –3/6 or 4/6

7. Rate of Increase in Indian Population Per Year = 1,55,31,000 Per Month = 12,73,033 Per Day = 42,434 Per Hour = 1,768 Per Minute = 29

8. Types of cord blood banks Public banks Use not restricted. No remuneration collected Usage subject to availability Private banks For use of the family Facility paid for by the family Availability guaranteed

9. Distribution of banks world-wide Around 100 of which 75 are public banks 40 in US, 30 in the UK, 20 in Asia and 10 in Australia

10. Common Misconceptions "The baby or siblings will never need the stem cells if my family doesn't have a history of cancer." Doctors would never treat the child with his or her own cord blood  because it would contain the disease." “Cord blood collection takes important blood away from my baby”

11. Studies on Viability Proceedings of the National Academy of Sciences, Broxmeyer and his co-author – study conclusions Human cord blood frozen in 1985 and 1986 was able to grow in laboratory cultures with the same vigour as fresh cord blood. Such cells frozen for a decade and a half can be used successfully to treat patients.

12. Factors vital for transplant success The number of cells per kilogram of the patient's body weight b) HLA match Conclusively proved by John Wagner's research.

13. Status of cord blood transplants Around 6000 transplants done world-wide Around 20 done in India (reported cases) 5 done in Chennai (Thalassemia and Leukemia)

16. Frequent applications Acute and Chronic Leukemias Myelo-dysplastic Syndromes Stem cell disorders Myelo-proliferative disorders Lympho-proliferative disorders Phagocyte disorders Inherited platelet abnormalities Inherited metabolic disorders Histiocytic disorders Inherited RBC abnormalities Inherited immune system disorders Plasma cell disorders Solid tumours Other inherited disorders

17. Umbilical Cord Transplants are Effective in Adults with Leukemia Reference: Arcese W, Rocha M, Labopin M, et al. Unrelated cord blood transplant in adults with haematologic malignancies. Bone Marrow Transplantation 2005;55 (supplement 2):S88, abstract number O413.

18. The Heacock Family

19. Myelo Dysplastic Syndrome (MDS) Umbilical cord transplants in 12 patients with advanced (MDS) . Two years following therapy, 76% of patients were alive and cancer-free. http://www.bloodjournal.org/cgi /reprint/2002-12-3917v1.pdf. Accessed March 3, 2003.

20. Stem Cell Transplants in tumours Relapsed Wilms' tumor – autologous or allogeneic transplants along with chemotherapy is effective Peripheral T-Cell Lymphoma –Spanish study on 115 patients with T-cell lymphoma in the Annals of Oncology. Study findings: High-dose chemotherapy (HDC)and an autologous stem cell transplant is effective for peripheral T-cell lymphoma, particularly early in the course of the disease. Five years following therapy, had a survival rate of 80%, with 79% remaining free of cancer. Recurrent Mantle Cell Lymphoma - Mini Transplants Effective

21. Ovarian Cancer Trial in Newly-diagnosed patients with advanced ovarian cancer – Nov 1st 2004Transplant and High-Dose Chemotherapy Studied  Criteria of success Increased survival rate by 15% Double the duration of remission from the current 11 months remission average to 22 months

22. Breast and Brain Tumours Michigan Researchers ? Tissue from 9 human breasts and metastatic tissue examined ? Specific markers on stem cells identified ? 2 different groups of cells

23. Ongoing trials Cardiac Disease Diabetes Multiple Sclerosis Muscular Dystrophy Parkinson’s Disease Spinal Cord injuries Stroke

24. Transendocardial,autologous bone marrow cell transplantation of severe, chronic IHD- Circulation 2003, 107 :2294 - 2302 Conclusions : The present study demonstrates the relative safety of intra myocardial injections of bone marrow derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function

25. An alternative to surgery ? In cardiac patients :Cardiac tissue repair and regeneration using stem or parent cells from their organs – possible in a few years. Heart-to-heart transfer better prospects than transplanting adult bone marrow cells into heart patients .Trial to re-transplant 13 patients with cardiac failure at JHU

26. To free diabetics of insulin injections – Hindu July 14, 2005 Dr Alan Colman – Embryonic Stem Cell International, Singapore Animal tests in progress Creation of universal cell lines using “stealth technology”

27. Bone Marrow Stem cells in Diabetes – Ramesh R. Bhonde

28. Spinal cord Injury - Human Trials China : 300 patients using OEC from fetal olfactory tissue Australia: 8 patients using autologous cultured OEC obtained from nasal mucosa Portugal: 20 patients using autologous olfactory tissue Huang H et al. Influence of patient’s age on functional recovery after transplantation of OEC into injured spinal cord. Chin Med J (Engl). 2003; 116 (10): 1488 – 91.

29. Stroke Phase 1 Uncontrolled trial- 12 individuals with basal ganglia (BG) stroke – Stem cell inj showed functional improvement. Phase 2 with controls – 14 patients with BG strokes.4 received 5x106 and 2 receiving 10x106 improved. Vol 1 No 3 2004 Reviews in Neurological Diseases

30. Stem cell transplant in TBI Neurological improvement in rats with cortical impact injury Intralesional BrdU labelled bone marrow derived mononuclear cell suspension Intracerebral/Intravenous MSC injection MSC (cultured with neurotrophic growth factors) transplant adjacent to lesion (Mahmood et al –; J Neurosurgery 2001; J Neurotrauma 2002; Neurosurgery 2003; Neurosurgery 2004)

31. Abby and Anoxic Brain Injury An Answer for AbbyUnwilling to give up Cathy, contacted Dr. Joanne Kurtzberg at Duke University in North Carolina. "She told me that since we had saved Abby's cord blood and were willing to bring her to North Carolina, that she would do the transfusion," explained Cathy. "I've already seen results. Just two weeks after the procedure, she really looked at me and smiled; we connected for the first time," said Cathy. "Before she wasn't tracking objects with her eyes, and now she is. We have hope. As far as I'm concerned it's working. It really is working."

32. Unbelievable , but true… Elaine Fuchs, cell biologist at Rockefeller University " In mammalian skin, each hair follicle contains a reservoir of stem cells, known as the bulge, which can be mobilized to regenerate the new follicle with each hair cycle and to generate new epidermis during wound repair” Published in Cell, Volume 118, Number 5, September 3, 2004, pages 635-648.

33. Stem cells from fat used to repair girl's skull - AP Dec. 20, 2004

34. CCMB, LVPEI and Sarojini Eye Hospital-Wednesday, March 02, 2005 250 patients who had undergone stem cell therapy - 70 % had vision restored. The next step –Develop a hemi-cornea Final goal- Reconstruct an entire cornea from a suitable stem cell source

35. Applications in Plastic Surgery Fillers Breast implants Reconstruction of bone, cartilage Skin graft- in burns and other skin diseases Baldness

36. Published work Multi lineage cells from human adipose tissue: Implications for cell-based therapies: Patricia Zuk et al. Tissue engineering, Vol 7/2, 2001; 210-227 Tissue engineered cartilage with human bone marrow mesenchymal stem cells:Arch. Facial & Plastic surgery, 2005 Realistic Prospects for Stem cell therapeutics:Daley et al, Am.soc.Hemat, 2003,398-416

38. Future Stem cell applications Alzheimer’s Disease Lupus Rheumatoid Arthritis Liver Diseases

39. The Indian Scene Some Transplant Centres in India Tata Memorial Hospital, Mumbai Adyar Cancer Centre, Madras Apollo Specialty Hospital, Madras, Apollo Hospital, Global Hospitals, NIMS, Hyderabad Christian Medical College, Vellore Narayana Hruduyalaya , Bangalore R&R Army Hospital, AIIMS , New Delhi Inlaks Hospital, Armed Forces Medical College, Pune Sanjay Gandhi PGIMS, Lucknow

40. Ongoing Research Identifying factors affecting homing and engraftment Cell expansion / ex vivo culture / “selective” cell differentiation techniques Fat stem cell differentiation into other cell types Olfactory Ensheathing cells (OEC) down differentiation

41. Homing and engraftment A study in the August 13 Science reveals that the inhibition or genetic deletion of the peptidase CD26 on donor stem cells increases transplantation efficiency. A clue to a way to expand stem cells came from the observation that inhibition of CD26’s peptidase activity on the molecule CXCL12, which is though to be involved in the homing of stem cells, might therefore increase stem cell homing and engraftment. Being studied in mice -Broxmeyer, lead author Kent Christopherson

42. Matthew Farrow “Half a cup-full of cord blood might provide us with enough stem cells to save a child” Professor Hal Broxmeyer, Indiana University School of Medicine