title: The CD133+ cell as advanced medicinal product for myocardial and limb ischemia.
abstract: Ischemic diseases are the major cause of death and morbidity in Western countries. In the last decade, cell therapy has been suggested to be a promising treatment both in acute/chronic myocardial and peripheral ischemia. Different cell lineages have been tested, including endothelial progenitor cells. A subpopulation of bone marrow-derived immature ECPs, expressing the highly conserved stem cell glycoprotein antigen prominin-1 or CD133 marker, was shown to possess pro-angiogenic and antiapoptotic effects on ischemic tissues. The mechanisms implicated in CD133+ cells ability to contribute to neovascularization processes have been attributed to their ability to directly differentiate into newly forming vessels and to indirectly activate pro-angiogenic signaling by paracrine mechanisms. A large body of in vivo experimental evidences has demonstrated the potential of CD133+ cells to reverse ischemia. Moreover, several clinical trials have reported promising beneficial effects after infusion of autologous CD133+ into ischemic heart and limbs exploiting various delivery strategies. These trials have contributed to characterize the CD133+ manufacturing process as an advanced cell product (AMP). The aim of this review is to summarize available experimental and clinical data on CD133+ cells in the context of myocardial and peripheral ischemia, and to focus on the development of the CD133+ cell as an anti-ischemic AMP.
authors.affiliation: 1 Laboratory of Vascular Biology and Regenerative Medicine , Centro Cardiologico Monzino-IRCCS, Milan, Italy .
authors.forename: Dario
authors.initials: D
authors.lastname: Bongiovanni
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bassetti
authors.forename: Elisa
authors.initials: E
authors.lastname: Gambini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gaipa
authors.forename: Giacomo
authors.initials: G
authors.lastname: Frati
authors.forename: Felice
authors.initials: F
authors.lastname: Achilli
authors.forename: Paolo
authors.initials: P
authors.lastname: Scacciatella
authors.forename: Corrado
authors.initials: C
authors.lastname: Carbucicchio
authors.forename: Giulio
authors.initials: G
authors.lastname: Pompilio
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D064592:Autografts; D005121:Extremities / Q000098:blood supply; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000628:therapy; D017202:Myocardial Ischemia / Q000378:metabolism / Q000628:therapy; D018919:Neovascularization, Physiologic; D010455:Peptides; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides