Safety and Effect of Adipose Tissue-Derived Stem Cell Implantation in Patients With Critical Limb Ischemia – A Pilot Study –

Han Cheol Lee; Sung Gyu An; Hye Won Lee; Jin-Sup Park; Kwang Soo Cha; Taek Jong Hong; Jong Ha Park; Sun Young Lee; Sang-Pil Kim; Yeong Dae Kim; Sung Woon Chung; Yong Chan Bae; Yong Beom Shin; Jeung Il Kim; Jin Sup Jung

doi:10.1253/circj.CJ-11-1135

Regenerative Medicine

Safety and Effect of Adipose Tissue-Derived Stem Cell Implantation in Patients With Critical Limb Ischemia

– A Pilot Study –

Han Cheol Lee, Sung Gyu An, Hye Won Lee, Jin-Sup Park, Kwang Soo Cha, Taek Jong Hong, Jong Ha Park, Sun Young Lee, Sang-Pil Kim, Yeong Dae Kim, Sung Woon Chung, Yong Chan Bae, Yong Beom Shin, Jeung Il Kim, Jin Sup Jung

Author information

Han Cheol Lee
Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Sung Gyu An
Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Hye Won Lee
Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Jin-Sup Park
Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Kwang Soo Cha
Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Taek Jong Hong
Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Jong Ha Park
Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Sun Young Lee
Department of Physiology, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Sang-Pil Kim
Department of Thoracic & Cardiovascular Surgery, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Yeong Dae Kim
Department of Thoracic & Cardiovascular Surgery, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Sung Woon Chung
Department of Thoracic & Cardiovascular Surgery, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Yong Chan Bae
Department of Plastic Surgery, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Yong Beom Shin
Department of Rehabitation, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Jeung Il Kim
Department of Orthopedic Surgery, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital
Jin Sup Jung
Department of Physiology, College of Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital

Keywords: Adipose tissue, Angiogenesis, Cell therapy, Critical limb ischemia, Mesenchymal stem cell

JOURNAL FREE ACCESS

2012 Volume 76 Issue 7 Pages 1750-1760

DOI https://doi.org/10.1253/circj.CJ-11-1135

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Abstract

Background: Treatment of critical limb ischemia (CLI) by bypass operation or percutaneous vascular intervention is occasionally difficult. The safety and efficacy of multiple intramuscular adipose tissue-derived mesenchymal stem cells (ATMSC) injections in CLI patients was determined in the study. Methods and Results: The study included 15 male CLI patients with ischemic resting pain in 1 limb with/without non-healing ulcers and necrotic foot. ATMSC were isolated from adipose tissue of thromboangiitis obliterans (TAO) patients (B-ATMSC), diabetes patients (D-ATMSC), and healthy donors (control ATMSC). In a colony-forming unit assay, the stromal vascular fraction of TAO and diabetic patients yielded lesser colonies than that of healthy donors. D-ATMSC showed lower proliferation abilitythan B-ATMSC and control ATMSC, but they showed similar angiogenic factor expression with control ATMSC and B-ATMSC. Multiple intramuscular ATMSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSC implantation showed formation of numerous vascular collateral networks across affected arteries. Conclusions: Multiple intramuscular ATMSC injections might be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities. (Circ J 2012; 76: 1750–1760)

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