Unravelling mechanisms of stem cell depletion in diabetes
Research type
Research Study
Full title
Unravelling mechanisms of stem cell depletion for preservation of regenerative fitness in patients with diabetes
IRAS ID
126417
Contact name
Paolo Madeddu
Contact email
Sponsor organisation
Research Enterprise Development
Research summary
When a growing fatty plaque or clot blocks the passage of blood in a vessel, the nurtured tissue becomes starved and cells can die. This condition is called ischemia. Medical research is now focusing on stem cells (SC) as a new means to mend the damage caused by ischemia. SC from the bone marrow (BM) are particularly attractive since they participate in processes of vascular repair. In addition, BM SC have been used since long time to treat patients with blood diseases. Recent clinical studies using BM SC in patients with heart attack or limb ischemia show that transplantation of patient's own SC improves the clinical outcome. However, the therapeutic activity of SC might be reduced as a consequence of risk factors. Diabetes mellitus is one major risk factor for ischemic disease. We discovered that SC in BM of diabetic patients are reduced in number and substituted with fat. We also found a reduction of small vessels in BM. Microvascular disease, known as microangiopathy, is responsible for complications of diabetes, such as loss of vision, foot ulcers and renal failure. The goal of the present research is to determine if microangiopathy is the culprit OF SC shortage in the BM of diabetic patients. This could lead to new solutions for preservation of the integrity of BM SC and improvement of current SC-based therapies. To this aim, we will perform a series of laboratory studies on bone surplus from diabetic and non-diabetic patients undergoing orthopaedic surgery at Southmead Hospital (Bristol, UK). These will consist of examining the BM structure by histology and SC and vascular cells in culture. We will also investigate molecular mechanisms that are altered as a consequence of diabetes with the final objective to prevent and reduce the damage induced by high glucose.
REC name
Wales REC 4
REC reference
14/WA/1005
Date of REC Opinion
29 May 2014
REC opinion
Favourable Opinion