bone marrow mononuclear cells vs mesenchymal stem cells in diabetic patients with chronic limb ischemia

Conditions: Chronic Limb-threatening Ischemia; Diabetes Mellitus

Summary: patients in the severe stages of chronic limb-threatening ischemia (clti) are prone to amputation and death, leading to poor quality of life and a great socioeconomic burden. there is an urgent need to develop an effective therapeutic strategy to treat this disease. in this context, autologous bone marrow mononuclear cells (bm-mnc) and allogeneic mesenchymal stem cells derived from different sources have emerged as promising therapeutic approaches for this condition.

comparison of the therapeutic potential of bm-mnc vs. allogeneic wharton jelly-derived mesenchymal stem cells (allo-wj-mscs) in diabetic patients with clti. twenty-four type 2 diabetic patients in the most severe stages of the clti (category 4 or 5 in rutherford's classification and transcutaneous oxygen pressure (tcpo2) below 30 mm hg were enrolled and randomized to receive 15 injections of (i) bm-mnc (7.197x106 ± 2.984 x106 cells/ml each with 2% of autologous serum) (n=7), (ii) allo-wj-mscs (1.333 x106 cells/ml each with 5% of human serum albumin serum) (n=7) or (iii) placebo solution (1 ml saline solution with 2% of autologous serum) (n=10), which were administered into the periadventitial arteries. the follow-up visits were at months 1, 3, 6, and 12, to evaluate the following parameters: (i) rutherford classification (0 to 6) (ii) tcpo2 (mmhg) (iii) wound closure (area cm2) (iv) pain (visual analogue scale (0-10) (v) pain-free walking distance (m) (vi) revascularization and limb-survival proportion during follow-up (vii) the quality of life (eq-5d questionnaire).

Eligibility criteria:
inclusion criteria: * adult male or female, 40 years of age or over (until 85 years old) * tcpo2 ≤ 30 mmhg. * diagnosis of diabetes. * patients with signs of critical ischemia such as (i) ulcer that does not heal, (ii) necrosis or loss of tissue, (iii) pain at rest, and (iv) intermittent claudication. * basal rutherford classification stage 3 to 5. * non-revascularizable patients due to comorbidities and/or anatomy. * patients that despite revascularization (vascular surgery), have adequate distal beds to perfuse the limb. * ankle/brachial index less than 0.4. * stenosis or occlusion of the infrapatellar arteries. exclusion criteria: * participants that do not sign the informed consent. * presence of osteomyelitis. * hemodynamic instability (map\<65 mmhg or vasopressor requirement). * any acute systemic infectious disease process. * severe sepsis. * uncontrolled coagulopathy. * condition of cancer. * use of immunosuppressive or cytotoxic drugs * alterations of the bone marrow that do not allow the adequate extraction of the components to be used as: acute leukemia, chronic leukemia, marrow aplasia, myelodysplastic syndrome, and myelophthisis. * contraindication of sedation for bone marrow aspirate. * patients who have suffered in a period \< six months of myocardial infarction, disease cerebrovascular or coronary intervention. * patients with liver failure indicated by serum transaminases (aspartate aminotransferase and alanine aminotransferase), with values twice the normal limit. * any acute or chronic contagious disease including hepatitis b, hepatitis c, and hiv. * any other comorbidity that the treating vascular surgeon considers as a contraindication to cell treatments.

Keywords: bone marrow mononuclear cells mesenchymal stem cells