Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study

Abstract

The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry-storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6-month follow-up period. Four out of ten heart failure patients developed donor-specific de novo human leukocyte antigen (HLA) class I antibodies, and two out of ten patients had donor-specific HLA antibodies already at baseline. There were no clinical symptoms or changes in inflammatory parameters in the follow-up period that indicated an ongoing immune response. There was a tendency toward improvement in cardiac function after CSCC_ASC treatment at 6-month follow-up: left ventricular end systolic volume decreased and left ventricular ejection fraction increased. In addition, exercise capacity increased. These changes were independent of the presence or absence of HLA antibodies. It is concluded that the newly developed cryopreserved product CSCC_ASC from healthy donors was a safe and feasible treatment. We observed a tendency toward efficacy in patients with IHF. These findings have to be confirmed in larger placebo controlled clinical trials. Stem Cells Translational Medicine 2017;6:1963-1971.

Keywords: Adipose stem cells; Cardiac; Cellular therapy; Clinical trial; Mesenchymal stem cells; Somatic cell therapy; Stromal cells; Tissue regeneration.

Figure 1

Cardiac function, exercise capacity and symptoms before and 6 months after treatment with Cardiology Stem Cell Centre adipose‐derived stromal cell. Mean ± SD. Abbreviations: KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEDV, left ventricle end‐diastolic volume; LVEF, left ventricle ejection fraction; LVESV, left ventricle end‐systolic volume; NYHA, New York Heart Association classification.

Figure 2

The influence of development of donor‐specific tissue type antibodies on cardiac function, exercise capacity, and symptoms before and 6 months after treatment with Cardiology Stem Cell Centre adipose‐derived stromal cell. Mean ± SD. The * in LVESV indicates that the SD is outside the lower border of the figure. Abbreviations: 6MWT, 6‐minute walking test; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEDV, left ventricle end‐diastolic volume; LVEF, left ventricle ejection fraction; LVESV, left ventricle end‐systolic volume; NYHA, New York Heart Association classification; QoL, quality of life.