Angiographic Demonstration of Neoangiogenesis after Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Diabetic Patients with Critical Limb Ischemia

Abstract

Critical limb ischemia in diabetic patients is associated with high rates of morbidity and mortality. Suboptimal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10 6 cells) in 20 diabetic patients with severe below-the-knee arterial ischemia. Although the time course of clinical effects differed among patients, after 12 months of follow-up all patients presented a notable improvement in the Rutherford-Becker classification, the University of Texas diabetic wound scales, and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischemic areas and promotes remarkable clinical improvement.

Preconditioning with VEGF Enhances Angiogenic and Neuroprotective Effects of Bone Marrow Mononuclear Cell Transplantation in a Rat Model of Chronic Cerebral Hypoperfusion

“…Some phase I/II clinical trials also have shown that BMMNC transplantation can improve clinical outcomes of patients with middle cerebral artery occlusion (MCAO) [11–14]. In fact, several independent groups have reported that BMMNC transplantation significantly reduces ischemia-induced impairment and increases vascular density and blood flow in both acute and chronic ischemic disorders, such as cardiovascular disease [15], peripheral arterial disease [16], and diabetic foot [17]. However, little research has examined the effects and possible mechanisms of BMMNC transplantation in chronic cerebral hypoperfusion.…”

Role of Serum Levels of Angiogenic Cytokines in Assessment of Angiogenesis after Stem Cell Therapy of Diabetic Patients with Critical Limb Ischemia

“…Values are median ± interquartile endostatin (pg/ml) and median ± interquartile transcutaneous oxygen pressure (TcPO 2 ; mmHg) over time. which is currently not available or requires special techniques (19).…”

Autologous transplantation of CD34+ bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia

“…cells persistently increased for 1 month after the treatment only in the responders (Kajiguchi et al 2007). Similarly, neovasculogenesis in CLI diabetic patients was evaluated after infusion of unfractionated autologous BMderived mononuclear cell generating a significant increase in the vascular network in ischemic areas and promoting remarkable clinical improvement (Ruiz-Salmeron et al 2011).…”