BACKGROUND
The Kidney Dialysis Foundation’s (KDF) existing mission to look after the well being of kidney patients stricken with end stage kidney diseases, the Board of KDF has embarked on its next strategic mission to identify and support research work that lead to the prevention and cure of kidney failure due to diabetes and other complications. To facilitate this, the Memorandum and Articles of Association of the KDF was amended on 7 December 2006 and consent granted from the Commissioner of Charities on 15 March 2007. The Board of Directors on 25 May 2007 restricted fund designated “Research Fund” be set up.

The 1:1 government matching grant applied by the National University of Singapore has recently been approved and added to the KDF-NUS Research Fund. This would significantly aid us in making an important contribution in this area where the possibility of getting a new form of treatment for these patients is potentially in sight.

AREAS OF RESEARCH
As 50% of the new dialysis patients are due to diabetic complication of the kidney, a cure of diabetes will reduce the need for dialysis drastically. Through research, KDF aims to move up-stream and support research projects that will lead to the prevention of kidney failure and the need for expensive dialysis treatment. The other possible areas of research would be in area for alternative therapy to replace the existing dialysis treatment

RESEARCH ADVISORY COMMITTEE
To facilitate the review of research projects for their scientific and medical merits, the Board of Directors have commissioned the Research Advisory Committee to be set up under the Chairmanship of Prof Yap Kim Hui, Senior Consultant, Head, Division of Paediatric Nephrolog, Immunology and Urology, National University of Singapore. Other members of the Research Advisory Committee are Associate Professor Lina Choong, Associate Professor Evan Lee and Dr Grace Lee.

WORKING RELATIONSHIP WITH NATIONAL UNIVERSITY OF SINGAPORE
A working relationship is being established with the Yong Loo Lin School of Medicine, National University of Singapore, to provide the resources and infrastructure required to monitor and evaluate the progress of specific projects funded by the KDF Research Fund.  To achieve this, NUS and KDF have set up a Selection and Review Committee. This Committee comprises of Associate Professor George Yip, Assistant Dean (Grants) as the Chairperson and Professor Vathsala and Professor Yap Hui Kim as members for the period 2011 to 2015.

FIRST RESEARCH PROJECT SPONSORED BY THE KDF-NUS RESEARCH FUND
The NUS Selection and Review Committee has reviewed and selected to support the research work on Gene and Cell Therapy of Diabetes Mellitus: Derivation of insulin producing cells and differentiation and genetic modification of progenitor cells. This KDF-NUS Gene Therapy and Cell Therapy is a project led by Professor Sir Roy Calne, Visiting Professor in the Dept of Medicine and Dept of Surgery, NUS. He is Emeritus Professor of Surgery at the University of Cambridge and is a pioneer in organ transplantation. The local Investigators are Professor Lee K O, Dept of Medicine, NUS, and Dr Gan Shu Uin, Dept of Surgery, NUS. The project aims to find a gene and cell therapy for Diabetes.

Diabetes is the main cause of severe kidney disease requiring dialysis in Singapore and worldwide. Diabetes affects nearly 10 percent of the adult population in Singapore. In diabetes, there is a deficiency of insulin and this leads to high blood sugar leading to ‘diabetes mellitus’. The effects of long term high sugar result in complications from damage to the kidneys, eyes, blood vessels and other vital organs leading to patient morbidity and mortality. Unfortunately, current drug treatment regimes do not eradicate the disease, and medication has to be continued throughout life. Some patients get transplants of the pancreas gland (together with a kidney transplant in some patients; and in some patients, only the islets that secrete insulin are transplanted), and this cures their diabetes as well. However, the number of pancreas available for such transplants is far outnumbered by the huge number of patients with diabetes. So there is great need to find some other source of insulin secreting cells that can be transplanted into patients with diabetes. A special difficulty in this area of research of getting a cell that makes insulin when needed after eating, and then to stop when there is no need for the insulin anymore. This fine regulation is essential or else the blood sugar gets too low and this is dangerous for the patient.

KDF-NUS Gene Therapy and Cell Therapy
The research aims to find cell that are readily available and get these cells to produce insulin.

Umbilical cord cells
The team has been working on cells from the umbilical cord. There is no problem with supply as umbilical cord is normally discarded. At the moment, these umbilical cord cells can grow and mature in the direction of the pancreas cells. There have been some success but the cells do not secrete insulin all the time. In one of the projects, the team has used a virus to put in the insulin gene so that these cells secrete insulin. When these cells were put into diabetic mice, these cells were able to lower the blood sugar and improve the diabetes. In these earlier experiments, these cells had an extra advantage in that they secreted a substance called HLA-G which would also prevent immune rejection – and so the mice did not need any of the anti-immune drugs that normally would be given to prevent rejection. This was the work of a student who has got her PhD, and the work was published in Cell Transplantation this year (2011). The team hopes to continue the next stage of the research with umbilical cord cells, with and without using a virus to put in the extra insulin gene. Ideally, if the cells can be made to secrete enough insulin when needed and to stop when there is no need for the insulin anymore. This fine regulation is essential. However, the results so far (which is similar to what other researchers are finding in other parts of the world); is that there is not enough insulin secretion and extra insulin from putting in the insulin gene by using a virus or using other techniques, is necessary.

Bone Marrow cells
The team is also working with two other laboratories on another source of cells from the bone marrow – mesenchymal stromal cells (MSCs). There is already a lot of experience with using bone marrow in the treatment of leukemia and other cancers. Obtaining bone marrow is almost a routine procedure in many medical centres. The team has been working on these cells with Professor M Ghoneim in Egypt, and with Professor Kon OL in the National Cancer Centre in Singapore General Hospital in getting these Bone Marrow MSCs to secrete insulin. Professor Ghoneim has already succeeded in getting rat bone marrow cells to secrete insulin and cure diabetes in mice. By working with Professor Ghoneim and Professor Kon on larger animals, the team hopes that together they shall be able to make some advances using larger animal models with diabetes. They hope to be able to treat some dogs with diabetes with dog bone marrow in the next stage of their research.

The team is also working at the same time on human bone marrow MSCs to try to get these cells to secrete insulin with the fine regulation needed. The use of methods of culturing bone marrow MSCs that Professor Ghoneim has used in Egypt have had mixed results so far. The team hopes that in this next stage of the research, they shall be able to get these cells to make more insulin.