Study on the potential role of primary human pro-angiogene cells in betaceltransplantation

Project Details

Description

Diabetes mellitus (DM) is a serious metabolic disease that affects nearly 250 million people around the world, and is caused by a deficiency of the hormone insulin in the body. This results in an increased blood sugar level with the risk of secondary complications at the level of the kidneys, eyes, nerves and vasculature. The current standard treatment is substitution therapy where the patient injects several times a day with recombinant human insulin. However, this therapy does not lead to a stable normoglycaemic condition and thus can not prevent the diabetes-related complications. Therefore, alternative methods of treatment are sought in which the beta cell function can be endogenously maintained. Since the research into the production both of in vitro and in vivo new, fully functional beta cells is still insufficiently advanced for clinical application, the most useful technique is transplantation of Langerhans donor islets. However, this treatment also has a number of important limitations. For example, suppression of the immune system is required, which entails an increased risk of infection. Furthermore, in several long-term studies the function of the island was investigated and it was concluded that a progressive decrease in metabolic control occurs with time. In order to achieve a normoglycemic condition, a very large number of donor islands must initially be transplanted, which makes large-scale application of this method not feasible for the time being due to the shortage of organ donors. One of the main causes of insufficient glycemic control is cell death due to insufficient revascularization of the graft shortly after transplantation. My doctoral research aims to prevent the reduction of glycemic control by improving revascularization of the graft by co-transplanting with pro-angiogenic cells. The cell types on which we will concentrate are peripheral blood-derived blood outgrowth endothelial cells (BOECs) and bone marrow derived mesenchymal stem cells (MSCs), both from human donors. BOECs are endothelial cells that are formed in in vitro culture from mononuclear cells circulating in the blood. Recently, it has been shown that both in vitro and in vivo in a wound model at the level of the skin promote new blood vessel formation and wound healing (A. Luttun, unpublished data). MSCs are bone marrow-derived cells with a broad differentiation potential that are assigned both pro-angiogenic and immune modulating properties, and that make the adjuvant use of this cell type within a context of type 1 DM and beta cell transplantation very attractive. Both BOECs and MSCs are relatively easy to isolate from one donor and can be expanded in vitro, allowing autologous transplantation within type 1 DM patients.
AcronymIWT491
StatusFinished
Effective start/end date1/01/1031/12/13

Keywords

  • Cell Therapy
  • Prevention
  • Transplantation
  • Diagnostic Tests
  • Immunology
  • Cell Death and Survival
  • Islet Cell Pathology
  • Islet Cell Biology
  • Beta Cell Transplantation
  • Diabetes

Flemish discipline codes

  • Basic sciences
  • Biological sciences