Wound therapy with autologous bone marrow stem cells in diabetic patients with ischaemia-induced tissue ulcers affecting the lower limbs

Abstract

Previous studies suggest that autologous transplantation of bone marrow mononuclear cells is safe and effective in inducing therapeutic angiogenesis in patients with peripheral arterial occlusive disease (PAOD). Here we discuss a multidisciplinary approach to treating PAOD with a focus on the use of angiological diagnostic tools. We conclude that our autologous stem cell therapy is working in this patient and it is a potential new therapeutic option for diabetic patients with chronic foot ulcers induced by critical limb ischaemia.

Treatment of ischemic limbs by transplantation of G-CSF stimulated bone marrow cells in diabetic rabbits

“…In the G-PBMNC group, diabetic animals were injected subcutaneously with G-CSF (10 µg/kg) daily for five consecutive days. On day six, peripheral blood was collected and mononuclear cells (PBMNCs) were separated and injected into the quadriceps and adductor muscles in the ischemic limbs, along the excised artery at 10 points; each point was injected with 5X10 6 PBMNCs in a 100 µL of PBS. Group G-BMMNC was stimulated with G-CSF for five days.…”

“…[1][2][3] Given the poor prognosis associated with lower limb ischemia in diabetic patients, numerous interventions have been attempted, primarily based on the stimulation of angiogenesis to trigger the formation of collateral blood vessels. [1][2][3][4][5][6][7] Stem cell transplantation-based therapy is a novel and attractive potential treatment strategy for diabetic patients with limb ischemia. It is based on the rationale that delivery of endothelial progenitor cells into areas of ischemia may result not only in differentiation of the progenitors into endothelium, thereby contributing to angiogenesis, 8,9 but also produce numerous growth fac-tors that can stimulate angiogenesis via paracrine interactions with adjacent cells.…”

“…2,10,11 Several clinical studies have suggested that the lower limb ischemia in diabetic patients could be improved by autologous transplantation of either bone marrow mononuclear cells (BMMNC) or granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (G-PBMNC). [4][5][6][7][11][12][13] However, a proportion of these patients do not mobilize sufficient progenitors into the blood stream to produce adequate PBMNCs to allow for successful autologous transplantation. 14,15 To develop a more effective approach, we evaluated the efficacy of autologous transplantation of G-CSF-stimulated bone marrow mononuclear cells (G-BMMNC) to treat diabetic lower limb ischemia in an alloxanate-(AXL) induced diabetic rabbit model.…”

Stem Cell Transplantation for the Treatment of Peripheral Arterial Disease

“…Two patients in group A died after myocardial infarction, but this was unrelated to treatment [53]. Kirana et al [54] described a 60-year old type 2 diabetic patient with infected gangrenous ulcers of the 3 rd and 4 th left toes. The patient has severe stenosis of anterior tibial, posterior tibial and dorsalis pedis arteries, leading to critical ischaemia.…”

“…After amputation of the affected toes, he received intramuscular BMMNC transplantation. After 20 weeks, the stump had completely healed, and there were improvements in ABI, Laser Doppler reactive hyperaemia and TcPO 2 [54]. Higashi et al [55] studied the effect of BMMNCs in 7 patients with PAD.…”