2/26/2016. Types of Stem Cells: Agenda. Objectives

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1 PAMET, March 5, 2016 Umbilical Cord Blood for Public Banking and Research Regenerative Medicine: Curing disease by repairing or replacing organs and systems through cellular and tissue engineering Bladder disease Hearing loss Eye disease SUZANNE PONTOW, PHD CO-DIRECTOR, UMBILICAL CORD BLOOD COLLECTION PROGRAM, STATE OF CALIFORNIA, UC DAVIS INSTITUTE FOR REGENERATIVE CURES Agenda Types of Stem Cells: 1. Stem Cell 101: Focus on HSC/HPC 2. Umbilical cord blood in a transplant setting. 3. Explain the differences between public and private cord blood banking. 4. Relate current clinical laboratory tests being routinely used in the cord blood banking industry. Multipotent Mesenchymal Stem Cells (MSC) Hematopoietic Stem Cells (HSC) Pluripotent Embryonic Stem Cells Induced Pluripotent Stem Cells (ipsc) Adult Bone Marrow, Mobilized Peripheral Blood, Cord Blood, Placenta Embryos or Manipulated Adult cells Tissue-specific stem cells are called progenitor cells. Objectives attendees will learn about Basic stem cell biology and more about HSC/HPC, their use in transplantation and the laboratory tests used to characterize HSC/HPC from cord blood The use of cord blood in (bone marrow) transplant The history and missions of the state s UCBCP and our operations in the northern, central and southern CA areas. the future of cord blood use Donated IVF embryos Isolated from blastocyst Can be grown in culture Pluripotent Ethical debates 1

2 Neonatal Stem Cell Sources: Placental Tissues and Cord Blood Adult tissue cells + four genes = Pluripotent No ethical dilemma When will therapies using stem cells actually begin in people? Can make tissues: Multipotent Can become bone, cartilage, fat Paramedic of the Body Mobile Home to areas of injury/ischemia Secrete factors that help heal wounds, make new blood vessels Modulate immune system Invisible to immune rejection! Support for HSC/HPC Bone marrow Placenta 1956 First successful bone marrow transplantation from one human to another. Stem cells from the donor bone marrow were transplanted to regenerate the blood-forming system of a patient with leukemia. Hematopoietic Stem and Progenitor Cells (HSC/HPC) The Broxmeyer Studies set the foundation for modern cord blood transplants One CBU can yield enough cells for a transplant. (In Children). Cord blood can be transported before cryopreservation. The cells can be cryopreserved and stored in liquid nitrogen. The HSPCs from cord blood can reconstitute an immune system in mice. Yay!!! We can save mice. What about people? 2

3 First Transplant with Umbilical Cord Blood, 1988 What do you think of when you hear the term cord blood? 27 years ago in 1988, the first bone marrow transplant using cord blood was performed in France for a child with Fanconi Anemia (FA). The recipient, a 5 year old boy with severe Aplastic Anemia due to FA. The donor was a baby girl (sister), HLA-identical. FA was chosen because HLA-matched BM from a sibling was the current standard of care. Signs of engraftment at 22 days with complete subsequent hematological constitution and no GVHD. Cord Blood Transplant, 2016 This is what we think of Over 30,000 performed since 1988 globally FDA-approved and licensed product (HPC:CORD) Over 80 hematological diseases and malignancies Leukemias, Severe Anemias, Sickle Cell Disease, Bone Marrow Failures Unlicensed units used under an IND held by NMDP Single cord, dual cord and expanded HPC transplants Haplo transplantation Reduced intensity and other new pre-transplantation regimens Reduced GvHD In 2000 A joint Center for International Blood and Marrow Transplantation (CIBMTR) Eurocord study of 147 patients showed reduced GvHD in cord blood over bone marrow. GvHD reduced in both incidence and severity using cord blood HPC rather than bone marrow HPC One of the most significant advantages of cord blood over bone marrow. 3

4 The UCBCP: CA Health and Safety Code Sections Transplants for Minority and White Patients California state funded program ( ) for public cord blood banking administered from UC Davis Health System and deemed urgent $2 fee on birth certificates funds collection personnel and collection supplies Collection sites in hospitals serving a large, diverse patient population. Qualified cord blood banks will process, test, store and list the cord blood units on the National Registry. Distribution of non-clinical grade units to vetted researchers for cost recovery and program sustainability Why collect California s cord blood? Transplants by Patient Race & Ethnicity When a patient needs a new blood or immune system in place of their own, and they can t find a donor or matched cord blood unit in time, they die. Many Californians are not represented in the bone marrow donor registry or the cord blood inventory because of their race/ethnicity. Only California s cord blood can correct these deficiencies in the national inventory. Transplants for Minority Patients by Cell Source Role of Cord Blood in Transplants by Patient Race Hispanic/Latino 4

5 The UCBCP Mission: Equalize the probability that any patient requiring a transplant will find a match in the National Cord Blood Inventory. Set Up and Validation California state funding $2 fee on birth certificates Funding for collections at limited sites Collection sites in hospitals serving a large, diverse patient population. Qualified cord blood banks process, test, store and list the cord blood units on the National Registry. Units that do not fulfill the criteria for public banking, non-clinical units, are distributed for research UCBCP supports UC missions Recruiting Abolish healthcare disparities Celebrate diversity Provide life-saving clinical service Promote translational research Brochures get stuffed and stickered, in English and Spanish, according to SOP Brochures get delivered to clinics and OB offices, to moms on L&D, L&D waiting room and triage areas Presentations@ 2 birthing classes per month (1 weekend, 1 weeknight) for UCDHS Collector recruits through the initial consent process, and L&D nurses at UCDHS and Sutter have been crucial to gaining patient access and patient trust. Media: Jonny and/or myself have been interviewed for multiple news outlets including print, TV, internet radio and last week, Entercom radio (7 rock stations), a 22 min spot with a rock dj. Contracting Process Collection Process Assess potential collection site Collection Model Funding required (Personnel, supplies, shipping, etc) Birthrate and diversity Available space Executive support for participating in the program Pair with partner cord blood bank Contract negotiations: Meeting the needs of hospital and cord blood bank Contracts: Cord blood bank-hospital and UCBCP-hospital Informed consent upon arrival to triage or prior to arrival if informed during birthing class. In utero (OB) or ex utero (trained collector) collection of cord blood depending on hospital and/or cord blood bank requirements Shipment to partner cord blood bank within 36-48h Determination of total nucleated cell count (TNC) Maternal questionnaire for bankable units Maternal blood draw for bankable units Non-bankable units de-identified and distributed for research 5

6 Other Options: Private Banking and Research Current Human Stem Cell Clinical Trials at UC Davis Peripheral artery disease Non-healing ulcers, burns and wounds Non-union bone fractures Heart disease; cardiac infarction Blood and autoimmune disorders Traumatic brain injury Chronic pain spine Disc degeneration Eye degeneration Plus another 18 in the pipeline Clinical Trials: From the lab to the patient Shared Translational Lab incubator for clinical trials GMP Facility and MDs/ Hospital- Conduct the clinical trials Clinical Product Cancer Immuno mirna exosomes Cardiac Wound Liver Kidney Swallowing ALS Myoblast Bladder HD/ BDNF CLI/ VEGF HIV Bone Trachea Eye CLI/ Biomet Bone/Synthes TBI Vertebral fusion Disc repair/mesoblast Cardiac/Osiris Skin ulcers Approved therapies used: BMT, organ transplant, Skin expansion/grafting, Cord Blood transplant, Cell/matrix for wound healing UC Davis Good Manufacturing Practice Facility Retinal Degeneration Cellular product manufacturing for clinical trials/regulatory agency approvals 6

7 Not just for humans- clinical trials of stem cell therapy are also ongoing at the UC Davis School of Veterinary Medicine to treat dogs, cats, horses, and other companion animals Daisy received stem cells in her eye for our vision trial Bailey was injected With her own stem cells to treat lameness (AND we have a Cord blood bank for horses!) Whiskey had his jaw rebuilt after cancer, using tissue engineering Mojito can swallow again thanks to Dr. Belafsky, lasers, and tissue engineering Acknowledgements 7