1 / 29

Stem Cell Therapies for Type-1 Diabetes

Stem Cell Therapies for Type-1 Diabetes. Spinal Cord Society of New Zealand & Type-1 Diabetes?. Stem cells and making new tissues. Adult stem cells and autoimmunity. SCSNZ’s proposed trial(s). Spinal Cord Society NZ Inc.

garima
Download Presentation

Stem Cell Therapies for Type-1 Diabetes

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Stem Cell Therapies for Type-1 Diabetes Spinal Cord Society of New Zealand & Type-1 Diabetes? Stem cells and making new tissues. Adult stem cells and autoimmunity. SCSNZ’s proposed trial(s).

  2. Spinal Cord Society NZ Inc. • Who:Started by NoelaVallis& people with spinal cord injury (SCI), their families and care-givers in 1988. • Aim: To support research into treatment of SCI and achieve a “Cure” - Neurological repair and, or regeneration. • Strategy: Initially supported United States SCS. • Later funded training of a NZ Neuroscientist in USA. • Set up a Dunedin laboratory & a NZ-based research program! • Laboratory projects with specific translational research goals. • Development of clinical studies.

  3. Spinal Cord Injury • Spinal cord injury is an extremely complex issue.

  4. SCSNZ & Regenerative Medicine • Successful treatments will require a combination of approaches including: Stabilise – prevent further physical/metabolicdamage. Repair & reconstruct – fix and replace . Physiotherapy – relearn function. Stem Cell Therapies!

  5. What are Stem Cells? • Undifferentiated cell that can produce a differentiated cell or divide to produce another undifferentiated cell. • 3 Main types: Embryonic • Induced • Adult

  6. What are Stem Cells?

  7. Embryonic Stem Cells

  8. Embryonic Stem Cells Cartilage CNS Adipose Muscle Epithelium

  9. Induced Pluripotent Stem Cells Cartilage CNS Adipose Muscle Epithelium

  10. Stem Cells & Tissue Engineering

  11. Stem Cells & Tissue Engineering • Liver: human in mouse (iPSCs + adult SCs) • doi:10.1038/nature12271 0 days 2 days 3 days

  12. Stem Cells & Tissue Engineering • Retina: mouse eSCs doi:10.1038/nbt.2643 Induced: Real thing: Engineered cells inserted into real thing:

  13. Stem Cells & Tissue Engineering • Brain: human iPSCs doi:10.1038/nature12517 Not yet transplanted into mice: Human brain organoid:

  14. Stem Cells & Type-1 Diabetes • Grow a new pancreas in the lab from stem cells? • Not quite yet…. • Grow islet cells in the lab from stem cells? • Viacyte Inc. San Diego PEC-01 Cells implanted into mice develop into mature pancreatic like cells Insulin Somatostatin Glucagon

  15. Stem Cells & Type-1 Diabetes

  16. Type-1 Diabetes + A combination of factors. Genetic background Viral Infection? Autoimmune destruction of insulin producing cells. Pancreas T-cells destroy islet cells Type 1 Diabetes 15,000 NZers, increasing 5%p.a. Insulin dependent Devastating long term complications Type-1 diabetes

  17. Adult Stem Cells • Self renewal capability. • Not pluri-potent but multi-potent (more limited differentiation). • Can be isolated and grown in the lab from: • Bone marrow • Fat • Umbilical cord • Many other tissues

  18. Adult Mesenchymal Stem Cells Ectoderm Endoderm Mesoderm Bone Nerve Cartilage Fat Liver Cardiac muscle Skeletal muscle Pancreas

  19. Adult Mesenchymal Stem Cells Immunomodulation

  20. Trial of Zhao et al. 2012, Participants. • Median age: 29 years, range 15 - 41. • Median diabetic history: 8 years, range 1 – 21. • Number of participants: • 15 type-1 diabetics. • 12 treated. • 3 controls .

  21. Patient monitored for changes in diabetes status. T cells mixed with umbilical cord blood stem cells in the lab T cells infused back to patient to protect regenerating islet cells T cells from patient collected. Trial of Zhao et al. 2012, Procedure. Zhao Y, et al., 2012. Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 10:3.

  22. Trial of Zhao et al. 2012. Outcomes (12 weeks post treatment) Diabetes severity • SevereModerateControl (moderate) Insulin production • C-peptide levels (ng/ml) • +0.21+0.42-0.08 Lower normal baseline is 0.6 • HbA1c • -1.68-1.91-0.30 • Insulin dose • -25%-38%0.00 • Markers of immune response • CD4+CD25+Foxp3+ cells increased (Treg cells) • TGFb levels increased • Restoration of Th1/Th2/Th3 cytokine balance Results suggest autoimmune response was either stopped or attenuated allowing slow islet recovery & insulin production

  23. Clinical trials with stem cells. • Regulatory details are being worked out worldwide. • In NZ: • Standing Committee On Therapeutic Trials (SCOTT Committee). • Ethical approval from HDEC • Spinal cord injury trials take a long time and measuring benefit is multimodal. • Strategic decision to target an “easier” disease to get cells into clinical trial = Type-1 diabetes.

  24. Proposed trials at SCSNZ Trial 1 Bone marrow stem cells from patient grown and activated. T cells deactivated in patient. Bone marrow stem cells infused into patient. Trial 2 Patient monitored for changes in diabetes status. Patient monitored for changes in diabetes status. T cells deactivated by bone marrow stem cells in flask T cells infused back to patient to protect regenerating islet cells T cells from patient collected.

  25. Parameters to be monitored Efficacy measures • C-peptide levels • HbA1c • Insulin usage • Blood glucose level monitoring Immune measures • lymphocyte subsets, (CD4, CD8, B, NK) • IgG, IgA and IgM serum levels. • Tetanus toxoid antibody, anti-CMV and, or anti-EBV • Anti-Pneumococcal polysaccharide mix • CD4+ CD25+ FoxP3 positive lymphocytes. • T lymphocyte responses against i-IA-2, GAD, Insulin We will measure numbers and reactivity of relevant subsets of immune cells to look for changes following treatment.

  26. Autologous bone marrow MSCs Bone marrow aspirate taken Bone marrow stem cells isolated and grown Bone marrow stem cells tested for quality and stored frozen for trial Surface markers Karyotyping Pathogen screen Colony forming Differentiation Immunosuppression

  27. What we need…. Terumo BCT Quantum Cell Expansion System. • Closed cell culture system. • Highly reproducible growth conditions. • Single cylinder per patient. • About $300, 000. Trial Funding. • Establishment & commission: $1.0 million. • Trial costs: $0.9 million.

  28. Project Team Dr Jim FaedHaematology/Clinical Trials Dr Paul Turner Stem Cell Biology Dr Sarah YoungImmunology Prof. Jim Mann Diabetology Dr Ben Wheeler Diabetology

  29. Please have a look at… www.scsnz.org.nz/contact-us/ send us your details to receive free newsletter via email. “Chasing a Cure for Type 1 Diabetes” on Facebook, run by Sandra Grant.

More Related