title: Therapeutic strategies for cell-based neovascularization in critical limb ischemia.
abstract: Critical limb ischemia (CLI) causes severe ischemic rest pain, ulcer, and gangrene in the lower limbs. In spite of angioplasty and surgery, CLI patients without suitable artery inflow or enough vascular bed in the lesions are often forced to undergo amputation of a major limb. Cell-based therapeutic angiogenesis has the potential to treat ischemic lesions by promoting the formation of collateral vessel networks and the vascular bed. Peripheral blood mononuclear cells and bone marrow-derived mononuclear cells are the most frequently employed cell types in CLI clinical trials. However, the clinical outcomes of cell-based therapeutic angiogenesis using these cells have not provided the promised benefits for CLI patients, reinforcing the need for novel cell-based therapeutic angiogenesis strategies to cure untreatable CLI patients. Recent studies have demonstrated the possible enhancement of therapeutic efficacy in ischemic diseases by preconditioned graft cells. Moreover, judging from past clinical trials, the identification of adequate transplant timing and responders to cell-based therapy is important for improving therapeutic outcomes in CLI patients in clinical settings. Thus, to establish cell-based therapeutic angiogenesis as one of the most promising therapeutic strategies for CLI patients, its advantages and limitations should be taken into account.
authors.affiliation: Division of Vascular Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Samura
authors.affiliation: Center for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan. toruhoso@yamaguchi-u.ac.jp.|Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan. toruhoso@yamaguchi-u.ac.jp.|Center for Regenerative Medicine, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan. toruhoso@yamaguchi-u.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Hosoyama
authors.affiliation: Division of Vascular Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Division of Vascular Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Morikage
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D035002:Lower Extremity / Q000098:blood supply* / Q000473:pathology*; D018919:Neovascularization, Physiologic
keywords: Cell-based therapeutic angiogenesis; Clinical trials; Combination therapy; Critical limb ischemia; Hypoxic preconditioning; Peripheral blood mononuclear cells