Treatment of chronic limb threatening ischemia (CLTI) with autologous bone marrow-mononuclear cells: preliminary results of a clinical trial of an advanced therapy medicinal product

M Perez-Basterrechea(1) M Alvarez-Viejo(1) M A Fernandez-Rodriguez(1) E Martinez-Revuelta(1) J M Garcia-Gala(1) A Zanabili Al-Sibbai(2) M Alonso-Perez(2) A Fernandez-Verdugo(3) A Lozano-Blazquez(4) S Perez-Lopez(1)

1:Cell Therapy and Regenerative Medicine Unit. Hematology and Hemotherapy Department. Central University Hospital of Asturias (HUCA). Health Research Institute of Asturias (ISPA). Oviedo. 33011; 2:Vascular Surgery Department. HUCA. Oviedo. 33011; 3:Microbiology Department. HUCA. Oviedo. 33011; 4:Clinical Pharmacy Unit. HUCA. Oviedo. 33011

Chronic limb threatening ischemia (CLTI) is a pathology in which the obstruction of the arterial blood flow entails, in addition to the high risk of loss of the extremity, a high mortality, decreased quality of life (due to pain, both at rest and during movement, ischemic ulcers, etc) and high costs for the national health system. When surgical treatment, both open and endovascular, is not possible, limb amputation is a very common alternative in these patients, although this procedure also carries a high perioperative mortality and a high rate of reintervention. Bone marrow mononuclear cells (BM-MNCs) constitute a heterogeneous cell population, with proangiogenic and immunomodulatory properties, which have been used for several years in regenerative medicine. BM-MNCs have been applied to the treatment of critical lower limb ischemia previously, although there are few studies dealing with CLTI, and the published results are very heterogeneous (mainly due to differences in the treatment protocol used). Taking this into account, we propose to develop a clinical trial to validate the safety and efficacy of the use of autologous BM-MNCs in the treatment of CLTI according to the route of administration (IA, IM or IA+IM). This CT was authorized by the Spanish Agency of Medicines and Medical Devices (AEMPS) in 2021 and three patients have been treated to date (each received cells by a different route of administration). None of the patients treated have suffered limb amputation. Moreover, they have shown improvement of symptoms and QoL.