Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells in patients with advanced limb ischemia.

A substantial number of patients with severe peripheral arterial occlusive disease (PAOD) is left without technical options for surgical or endovascular treatment. Recent evidence suggests that bone marrow mononuclear cells (BMC) may promote collateral vessel formation in these patients. However, several critical aspects such as long-term safety, effect durability, and optimal administration mode require consideration. We evaluated feasibility and safety of exclusively intramuscular versus combined intramuscular/intra-arterial delivery of BMC in patients with severe PAOD who were not candidates for surgical or endovascular treatment.

The primary aim of our study was to test the feasibility and safety of exclusively intramuscular, and combined intramuscular/intra-arterial delivery of Bone marrow Mononuclear Cells (BMC) in patients with advanced without conventional options for surgical or endovascular treatment.

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Hospital admittance was planned in a short-stay setting (24-48 hrs). The harvest procedure was performed according to standard protocols for bone marrow donation for allogenic transplantation. 750 milliliter bone marrow was collected from the posterior iliac crest under epidural or general anesthesia. The suspension was filtered and subsequently concentrated in a final volume of 40 mL. Upon concentration of the BMC-fraction, the erythrocyte fraction was collected separately and reinfused to the patient.

The mononuclear cells were implanted approximately 4 h after bone marrow aspiration. The method of administration was randomly assigned to the patients using a random number table: either by local injection into the gastrocnemius muscle or by combined IM+IA delivery. The investigators were not blinded for the assignment. In case of total IM delivery, we implanted 1 ml using a 26-gauge needle on 40 sites, 1.5 cm deep, using the full surface of the gastrocnemius muscle. In patients assigned to the combined treatment arm, the volume of each IM injection was 0.5 ml. The remaining 20 ml was slowly infused after selective catheterization of the superficial femoral artery (or profunda femoral artery in case of occlusion of the SFA), performed according to the standard procedures within the department of radiology.