The Immune Disorders laboratory is headed by Professor Ed Stanley, and uses human pluripotent stem cells to create cell types that play a role in the development of the immune system and in autoimmune disorders (such as type 1 diabetes), to understand how the immune system develops, and to create strategies for regulating immune cell function.
Our laboratory uses stem cells to investigate the development of immune cells and how these can be used to understand autoimmune diseases such as type 1 diabetes, sometimes called Juvenile diabetes.
The immune system has two main arms which work together to prevent and clear infections and to eliminate defective cells that are not functioning correctly or have characteristics that could potentially be a health risk. Within this environment, it’s very important that immune cells can distinguish between normal cells and cells that are defective. In autoimmune conditions, this distinction can be lost, leading the immune system to attack cells that are normal. This scenario is thought to underlie the genesis of conditions such as type 1 diabetes.
Type 1 diabetes is a condition that affects around 130,000 Australians. It occurs when the immune system accidentally attacks and kills cells in the body that make insulin, the hormone that controls the level of glucose in the blood. This means that people with type 1 diabetes have to inject themselves with insulin 3 or 4 times a day and also frequently monitor their blood glucose by performing finger prick blood tests. It is unknown why the immune system attacks insulin producing cells.
As part of a wide collaboration involving other laboratories and institutes, we have recreated cells of the immune system that play a role in type 1 diabetes. Using stem cells, we have also created human insulin producing cells in the laboratory. Our major goal is to now combine these cells together to learn why the immune cells attack cells that make insulin and to find ways in which this attack can be prevented.
Making immune cells from people with type 1 diabetes
We have created immune cells from stem cells that are made from people with Type 1 diabetes. Because it is believed that immune cells cause type 1 diabetes, the generation of these cells in the laboratory will enable us to test if these immune cells are any way defective, and if they are, whether such defects can be corrected using drugs or other treatments.
Making insulin producing cells in the laboratory
We are generating insulin producing cells from stem cells made from people with type 1 diabetes. Insulin producing cells are the cell type that is missing in people with type 1 diabetes. These cells can be replaced with tissue provided by organ donors, but, as with all treatments that are dependent on organ donors, there are never enough donors to satisfy demand. This supply problem could be solved if it was possible to efficiently generate insulin producing cells from stem cells.
Costa M, Dottori M, Ng E, Hawes SM, Sourris K, Jamshidi P, Pera MF, Elefanty AG, Stanley EG. (2005) The hESC line Envy expresses high levels of GFP in all differentiated progeny. Nat Methods. 2(4):259-60.
Davis RP, Ng ES, Costa M, Mossman AK, Sourris K, Elefanty AG, Stanley EG. (2008) Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors. Blood. 111(4):1876-1884.
Elliott DA, 22 other authors, Elefanty AG*, Stanley EG*. (2011) NKX2-5eGFP/w hESCs for isolation of human cardiac progenitors and cardiomyocytes. Nat Methods. 8(12):1037-40. *Joint contributors
Micallef SJ ... Elliott DA, Sarangi F, Harrison LC, Keller G, Elefanty AG, Stanley EG. (2012) INS(GFP/w) human embryonic stem cells facilitate isolation of in vitro derived insulin-producing cells. Diabetologia. 55(3):694-706.
Kao T, Labonne T, Niclis JC, Chaurasia R, Lokmic Z, Qian E, Bruveris FF, Howden SE, Motazedian A, Schiesser JV, Costa M, Sourris K, Ng E, Anderson D, Giudice A, Farlie P, Cheung M, Lamande SR, Penington AJ, Parish CL, Thomson LH, Rafii A, Elliott DA, Elefanty AG, Stanley EG. (2016) GAPTrap: A Simple Expression System for Pluripotent Stem Cells and Their Derivatives. Stem Cell Reports. 7(3):518-526.
Ng ES, Azzola L, Bruveris FF, Calvanese V, Phipson B, Vlahos K, Hirst C ... Oshlack A, Mikkola HK, Stanley EG, Elefanty AG. (2016) Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros. Nat Biotechnol. 34(11):1168-1179.