421 ISSN 1746-0751 Regen. Med. (2012) 7(3), 421–428 Special RepoRt 10.2217/RME.12.17 © Jens Kastrup Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): study design Despite advances in medical treatment and sur- gical and percutaneous interventions, there is still a group of patients who suffer from refrac- tory angina or angina-equivalent dyspnea due to myocardial ischemia. Chronic myocardial ischemia is a result of a gradually occluded or significantly blocked coronary artery. Distal to the blockage, the formation of collateral vessels is an attempt to maintain the perfu- sion to the ischemic area. Frequently, however, this attempt from the body’s own endogenous mechanisms is inadequate and the results are myocardial hypoperfusion, loss of functional cardiomyocytes, diastolic and systolic dysfunc- tion and finally angina or angina-equivalent dyspnea [1] . The attempt to find a new treatment for these patients with refractory angina or angina-equiv- alent dyspnea, in spite of maximal treatment with conventional therapies, has led research- ers to investigate the potential of regenerative medicine using autologous or allogeneic stem cells isolated from different tissues [2] . Stem cells isolated from adipose tissue have been suggested as a new cell source for regenera- tive medicine within cardiology [3] . Presently, only this clinical trial using culture-expanded adipose-derived stromal cells (ADSCs) in patients with heart disease is registered in the clinical trial database (NCT01449032) [101] . However, there are two registered clinical tri- als using freshly isolated adipose-derived cells (ADCs) in patients with ischemic heart fail- ure: the PRECISE study and, in patients with acute myocardial infarction, the APOLLO study (NCT00426868 and NCT00442806, respectively). This article reviews the isolation and characterization of ADSCs and preclinical animal studies using ADSCs in experimental ischemic heart disease. In addition, it intro- duces the first-in-man prospective, random- ized, double-blind, placebo-controlled clinical trial, MyStromalCell Trial, using VEGF-A 165 - stimulated autologous ADSCs in patients with chronic ischemic heart disease and refractory angina. Adipose-derived stromal cells Adipose tissue is a mesodermally derived organ that consists of adipocytes of various sizes. Interspersed between these mature adipocytes is the stroma, which is itself composed of endo- thelial cells, smooth muscle cells, fibroblasts, leukocytes, macrophages and preadipocytes [4] . Zuk et al. were the first to isolate and identify a fraction of ADCs containing stem cells, also called the stromal vascular fraction [5] . ADCs contain an abundant population of multipotent ADSCs, approximately 2% of nucleated cells [6] , which is in concentrations approximately 100–300-times higher than the concentration of mesenchymal stromal cells (MSCs) in bone marrow [7] . It has been demonstrated that these Adipose tissue represents an abundant, accessible source of multipotent adipose-derived stromal cells (ADSCs). Animal studies have suggested that ADSCs have the potential to differentiate in vivo into endothelial cells and cardiomyocytes. This makes ADSCs a promising new cell source for regenerative therapy to replace injured tissue by creating new blood vessels and cardiomyocytes in patients with chronic ischemic heart disease. The aim of this special report is to review the present preclinical data leading to clinical stem cell therapy using ADSCs in patients with ischemic heart disease. In addition, we give an introduction to the first-in-man clinical trial, MyStromalCell Trial, which is a prospective, randomized, double-blind, placebo-controlled study using culture-expanded ADSCs obtained from adipose-derived cells from abdominal adipose tissue and stimulated with VEGF-A 165 the week before treatment. KEYWORDS: adipose-derived stromal cell n adipose tissue n cardiac repair n chronic ischemic heart disease n double-blind n intramyocardial injection n mesenchymal stem cell n mesenchymal stromal cell n MyStromalCell Trial n placebo-controlled trial n randomized n vascular endothelial growth factor Abbas Ali Qayyum 1 , Mandana Haack-Sørensen 2 , Anders Bruun Mathiasen 1 , Erik Jørgensen 1 , Annete Ekblond 2 & Jens Kastrup* 1,2 1 Cardiac Catheterizaion Laboratory 2014, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, 9, Blegdamsvej, DK-2100 Copenhagen Ø, Denmark 2 Cardiology Stem Cell Laboratory, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, 9, Blegdamsvej, DK-2100 Copenhagen Ø, Denmark *Author for correspondence: Tel.: +45 3545 2819 Fax: +45 3545 2705 jens.kastrup@rh.regionh.dk part of For reprint orders, please contact: reprints@futuremedicine.com