“Role of Stem Cells in Treatment of Diabetic Foot Ulcers"

Abstract

SUMMARY R ecently it has been shown that careful glucose control can significantly decrease the complications of diabetes. Much effort has been expended to help diabetics maintain near-normal glucose levels. Those patients who have been successful have much better outcomes. For a variety of reasons, however, good blood glucose control is not easily obtained in a many patients. Therefore, the management of the complications is still a major focus of medical care, known that diabetic foot ulcers are common and serious complications of chronic diabetes mellitus. Diabetic foot ulcers (DFUs) precede 85% of non traumatic lower extremity amputations (LEAs). Approximately 3-4% of individuals with diabetes currently have foot ulcers or deep infections. Among persons with diabetes, 15% develop foot ulcers during their lifetime. Their risk of LEA increases by a factor of 8 once an ulcer develops. At 2 years following transtibial amputation, 36% of these patients are known to have died. Pathophysiologic factors involved in the development of diabetic foot ulcers are neuropathy, arterial insufficiency, musculoskeletal abnormalities, and poor wound healing. Microbial pathogens and poor nutrition also play a key role and compromise the healing process. The initiating injury may be from acute mechanical or thermal trauma or from repetitively or continuously applied mechanical stress. Local wound care must be addressed once a plan for achieving adequate tissue perfusion has been established. Minimization of weight bearing is important because excessive pressure and shear force are major contributors to continued tissue injury also, systemic antibiotics are essential in infected wounds. Nonsurgical and surgical debridement of the wounds is the mainstay of treatment for removal of infected and traumatized tissues and are essential to effective healing of these wounds. However, the natural capacity of collaterals to remodel and enlarge to compensate for the reduced flow that occurs after occlusion of a major artery is rarely sufficient to restore maximal flow capacity to levels required under various stress conditions. In the late stages of peripheral vascular disease, progression of tissue hypoperfusion results in ischemic ulceration and gangrene. Rapid revascularization of injured, ischemic, and regenerating organs is essential for restoration of their physiologic function. Although both surgical bypass and endovascular procedures remain effective in improvement of the blood flow in the ischemic legs, not all the patients are candidates for intervention. The effort in the basic science laboratories has shown the safety of the therapeutic angiogenesis. Therapeutic angiogenesis, the process of growing collateral blood vessels to better perfuse ischemic tissue, has been thought as an up-coming treatment for symptomatic lower extremity peripheral arterial occlusive disease. However current treatment options for this disease carry high risk, limited efficacy or limited durability. Stem cell-based regenerative medicine therapies have been touted recently as a novel-therapeutic approach to treat and cure a wide range of disease. Both adult and embryonic stem (ES) cells can serve important sources of precursor cells to derive more mature cell potentially utilized for clinical applications. Bone marrow is a rich reservoir of tissue-specific stem and progenitor cells. Experimental and clinical studies have shown that endothelial progenitor cells are mobilized from bone marrow, migrate to ischemic tissue, and contribute to the neovascularization process in response to tissue ischemia. In patients suffering from peripheral arterial disease (PAD), the implantation of autologous whole bone marrow mononuclear cells into gastrocnemius muscle resulted in significant improvements of limb blood flow indicated by ulcer healing rate, painless walking distance and MRA. Also, local implantation of MSCs is a promising treatment method for skin wounds especially for chronic diabetic foot ulcers, showing significant increase in ulcer healing rates. Although advanced techniques are in great progress, but it is essential to strict to basic techniques and it should not be forgotten.