RT Journal Article
T1 REX-001, a BM-MNC Enriched Solution, Induces Revascularization of Ischemic Tissues in a Murine Model of Chronic Limb-Threatening Ischemia
A1 Rojas-Torres, Marta
A1 Jiménez-Palomares, Margarita
A1 Martín-Ramírez, Javier
A1 Beltrán-Camacho, Lucía
A1 Sánchez-Gomar, Ismael
A1 Eslava-Alcon, Sara
A1 Rosal-Vela, Antonio
A1 Gavaldá, Sandra
A1 Durán-Ruiz, M. Carmen
K1 Chronic limb-threatening ischemia
K1 Critical limb ischemia
K1 Stem cell therapy
K1 Revascularization
K1 Angiogenesis
K1 BM-MNC
K1 Bio-distribution assay
K1 Isquemia crónica que amenaza las extremidades
K1 Tratamiento Basado en trasplante de células y tejidos
K1 Células madre
K1 Animales
K1 Células de la médula ósea
AB Background: Bone Marrow Mononuclear Cells (BM-MNC) constitute a promising alternative for the treatment of Chronic Limb-Threatening ischemia (CLTI), a disease characterized by extensive blockade of peripheral arteries, clinically presenting as excruciating pain at rest and ischemic ulcers which may lead to gangrene and amputation. BM-MNC implantation has shown to be efficient in promoting angiogenesis and ameliorating ischemic symptoms in CLTI patients. However, the variability seen between clinical trials makes necessary a further understanding of the mechanisms of action of BM-MNC, and moreover, to improve trial characteristics such as endpoints, inclusion/exclusion criteria or drug product compositions, in order to implement their use as stem-cell therapy. Materials: Herein, the effect of REX-001, a human-BM derived cell suspension enriched for mononuclear cells, granulocytes and CD34+ cells, has been assessed in a murine model of CLTI. In addition, a REX-001 placebo solution containing BM-derived red blood cells (BM-RBCs) was also tested. Thus, 24 h after double ligation of the femoral artery, REX-001 and placebo were administrated intramuscularly to Balb-c nude mice (n:51) and follow-up of ischemic symptoms (blood flow perfusion, motility, ulceration and necrosis) was carried out for 21 days. The number of vessels and vascular diameter sizes were measured within the ischemic tissues to evaluate neovascularization and arteriogenesis. Finally, several cell-tracking assays were performed to evaluate potential biodistribution of these cells. Results: REX-001 induced a significant recovery of blood flow by increasing vascular density within the ischemic limbs, with no cell translocation to other organs. Moreover, cell tracking assays confirmed a decrease in the number of infused cells after 2 weeks post-injection despite on-going revascularization, suggesting a paracrine mechanism of action. Conclusion: Overall, our data supported the role of REX-001 product to improve revascularization and ischemic reperfusion in CLTI.
PB Frontiers
YR 2020
FD 2020-12-09
LK http://hdl.handle.net/10668/3793
UL http://hdl.handle.net/10668/3793
LA en
NO Rojas-Torres M, Jiménez-Palomares M, Martín-Ramírez J, Beltrán-Camacho L, Sánchez-Gomar I, Eslava-Alcon S, et al. REX-001, a BM-MNC Enriched Solution, Induces Revascularization of Ischemic Tissues in a Murine Model of Chronic Limb-Threatening Ischemia. Front Cell Dev Biol. 2020 Dec 9;8:602837
DS RISalud
RD Apr 7, 2025