Abstract 18595: Therapeutic Angiogenesis for Critical Limb Ischemia by Implantation of Autologous Adipose-Derived Regenerative Cells: A Clinical Pilot Study
Introduction: Therapeutic Angiogenesis by Cell Transplantation using autologous bone marrow-derived mononuclear cells (TACT-BM) represents a novel strategy for critical limb ischemia (CLI). However, patients with severe peripheral artery occlusive disease or multiple coronary risk factors such as diabetes mellitus or renal failure with dialysis exhibited poor responses to the TACT procedure. Adipose-derived regenerative cells (ADRCs) are a promising alternative source of autologous somatic stem cells for regeneration and repair of damaged tissue. In preclinical animal models, we reported that implantation of ADRCs augmented ischemia-induced angiogenesis and maintained myocardial capillary density in response to ischemia. Here, we have translated this technique called the TACT-ADRC strategy to human cases.
Methods: The TACT-ADRC trial is a single arm, non-randomized, open-label, historical controlled study designed to assess the safety and feasibility of intramuscular injection of ADRCs in the treatment of patients with CLI. The TACT-ADRC trial receives approval of the Ministry of Health, Labour and Welfare in Japan. Patients were eligible for enrollment if patients with CLI are not candidates for surgical revascularization. Adipose tissues were obtained by a liposuction of the subcutaneous abdominal fat. ADRCs were isolated using the Celution system (Cytori Therapeutics Inc.) and injected into the gastrocnemius of the ischemic limb. Primary outcomes were safety and feasibility of treatment, based on the occurrence of a major adverse cardiovascular event, the amputation free survival ratio, walking distance in 6 minutes, and the changes of rest pain and ulcer size during the 6-month follow-up.
Results and Conclusions: We performed the TACT-ADRC in 6 patients with CLI so far. At 6 month, no adverse events related to the TACT-ADRC occurred. No patients required major limb amputation, and ischemic ulcers were partly or completely healed during 6-month follow-up period. Moreover, significant clinical improvements were seen on pain rating visual analogue scale and in walking distance in all cases. In conclusion, we confirm that autologous ADRCs implantation is safe and feasible for achievement of clinical therapeutic angiogenesis in CLI.
Author Disclosures: K. Kondo: None. R. Hayashida: None. R. Shibata: None. T. Murohara: Research Grant; Significant; Astellas, Daiichi Sankyo, Dainippon Sumitomo, Kowa, MSD, Mitsubishi Tanabe, Nippon Boehringer Ingelheim, Novartis, Otsuka, Pfizer Japan, Sanofi-Aventis, Takeda, and Teijin. Honoraria; Modest; Bayer, Daiichi Sankyo, Dainippon Sumitomo, Kowa, MSD, Mitsubishi Tanabe, Nippon Boehringer Ingelheim, Novartis, Pfizer Japan, Sanofi-Aventis, and Takeda.
- © 2016 by American Heart Association, Inc.