CHITBR

History of the Centre for Islet Beta Cell Transplant and Regeneration and current achievements:

Diabetes mellitus is a common chronic disease that affects more than 2.2 million Canadians. For 10% of those with the disease, type 1 diabetes necessitates a lifetime of insulin dependence. Despite intensive medical therapy consisting of insulin injections, persons with diabetes suffer devastating microvascular complications, such as: nephropathy; retinopathy; neuropathy; cardiovascular disease; stroke; gangrene; and impotence. These complications yield huge social and economic burdens in Canada; however, two treatment options offer promise: best medical therapy and pancreatic islet transplantation. The Centre for Human Islet Transplantation and Beta-cell Regeneration (CHITBR) is conducting the first study to compare these treatments side-by-side.
CHITBR was formed to advance islet transplantation with a unique combination of clinical research and basic science. We have fully embraced the translational model of research and the ‘bench-to-bedside’ approach to ambitious projects that are likely to make a real impact on patient’s lives. Our group has one of the most active islet transplant programs in the world. Building on our team’s success, we have proposed the first randomized controlled trial, paralleled by mechanistic basic science studies, to compare an innovative protocol in islet transplantation with best medical therapy to improve a number of health outcomes and quality of life amongst type 1 diabetics. The overall aim is to prevent or reverse devastating complications of diabetes through islet transplantation by improving the paradigm of transplant immunosuppression and prolonging the survival of insulin-secreting cells.
The Director of the Research Centre, Dr. Warnock, GL has developed the Ike Barber Human Islet Transplant Laboratory located in the Research Pavilion at Vancouver General Hospital (Vancouver Coastal Health Research Institute). This laboratory performs human islet isolation, preservation, culture, viability studies and quality control testing. Since opening in 2002, ~30 human pancreases have been processed per annum, yielding high quality human beta cells suitable for collaborative clinical and basic research studies amongst Qualified Health Researchers and others in the local diabetes research community.

CHITBR enables ground-breaking islet transplantation research by funding 5 integrated Core Facilities:

Core I: Human Islet & Pancreatic Tissue Core (Leader: G. Warnock).
Mission - Isolate and distribute human islet cells for clinical transplant and beta cell regeneration studies.

Core IIA: In Vivo Beta Cell Function Core (Leader: B. Verchere).
Mission – Optimize islet graft survival and function in islet transplant models.

Core IIB: In Vitro Beta Cell Function Core (Leader: J. Johnson).
Mission -  Assessment of human islets using real-time analyses of beta-cell survival and function to improve graft quality.

Core III: Genetic and Molecular Engineering Core (Leader: T. Kieffer).
Mission – Engineering molecular solutions for islet transplantation.

Core IV: Immuno-monitoring Core (Leader: A. Mui).
Mission - Identifying and characterizing alloimmunity and autoimmunity in islet transplantation models.

A major objective of the CHITBR is to foster collaborations enabled by Core Facilities. Some notable achievements from the collaborations include:

• Improvements in human islet isolation.
• Initiation of a prospective cohort study of islet transplantation versus best medical therapy in Type 1 diabetes. (Arch. Surg 2005; Warnock, Fung, Verchere, Johnson).
• Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. (Nature Medicine 2006; McIntosh).
• Human T-cell responses to human islets by activation of B7-H4 pathways (Cell Transplantation, 2006; Metzger, Warnock).
• Use of novel approaches to enhance cultured human islet survival and function (Verchere, Marzban, Johnson, Kieffer, McIntosh, Warnock).
• Effects of glucagon-like peptide 1 (7-37) on beta cell function after human islet transplantation (Transplantation, 2007; Meneilly, Fung, Warnock).
• Effects of insulin on beta-cell apoptosis in human and mouse islets (PNAS 2006; Johnson, Warnock)

The Centre for Islet Beta Cell Transplantation and Regeneration continues to expand on these studies. For example, Drs. Kieffer, Verchere, Tan and Johnson (Warnock as a major collaborator) have opened a new study area in beta-cell regeneration supported by a five-year CIHR/JDRF New Emerging Team Grant. Drs. Kieffer, Johnson, Verchere, Piret and Warnock are also employing high-content, high-throughput screening approaches to identify novel compounds capable of promoting beta-cell differentiation, proliferation or survival with the help from a Stem Cell Network Team Grant. Each of the Principle Investigators in the CHITBR have individual grants aimed at furthering the goals of the Centre.
Members of the Centre regularly meet on an alternating week basis with beta cell research meetings, and clinical islet transplant research meetings to present new experimental results, formulate research agenda and share novel ideas in beta cell research. They discuss further collaborations, development of graduate training projects and grant applications.

The Centre has received funding for infrastructure from several significant sources. In 2002, a key linkage was forged with the CFI $9 million Infrastructure Award for the Centre of Research on Childhood Diabetes (Verchere, Warnock, Metzger, Bonnevie-Nielsen, Tan, Chantler et al). This provided for start-up funding for the Ike Barber Islet Laboratory renovations and equipment, together with matched funds from Mr. Ike Barber’s $2.5 million endowment for diabetes research (Warnock), and the P.A. Woodward Foundation (Warnock). The Centre has successfully supported group members for many grant applications for national and international funding. Members of the Centre currently hold 13 CIHR grants (Warnock, Verchere, Kieffer, Mui, Johnson, Helgason et. al), 7 Juvenile Diabetes Research Foundation (JDRF) grants (Johnson, Verchere, Bonnevie-Nielsen, Kieffer, Warnock et. al), 5 Canadian Diabetes Association grants (Verchere, Tan, Kieffer, Metzger, Johnson) as well as grants from NSERC, Stem Cell Network, MITACS (Piret) and Canadian Blood Services (Scott). In addition, we have achieved support for a Graduate Training Program in Transplantation, so that clinician-scientist trainees and basic research trainees can acquire skills in islet transplantation through a CIHR / MSFHR partnership grant in transplantation research training (Chung, Warnock, Mui). Group members have published more than 500 papers related to the Centre’s research focus.