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

• Published in: Stem cells translational medicine Vol. 6; no. 11; pp. 1963 - 1971
• Main Authors: Kastrup, Jens, Haack‐Sørensen, Mandana, Juhl, Morten, Harary Søndergaard, Rebekka, Follin, Bjarke, Drozd Lund, Lisbeth, Mønsted Johansen, Ellen, Ali Qayyum, Abbas, Bruun Mathiasen, Anders, Jørgensen, Erik, Helqvist, Steffen, Jørgen Elberg, Jens, Bruunsgaard, Helle, Ekblond, Annette
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.11.2017; John Wiley and Sons Inc
• Subjects: Adipose stem cells; Adipose Stem Cells/VSF; Adipose tissue; Adipose Tissue - cytology; Adult; Aged; Antibodies; Bioreactors; Cardiac; Cardiac Disease; Cardiology; Cardiovascular disease; Cell culture; Cellular therapy; Clinical trial; Clinical trials; Congestive heart failure; Coronary artery disease; Cryopreservation; Cryopreservation - methods; Cryopreservation - standards; Data analysis; Female; Heart failure; Heart Failure - etiology; Heart Failure - therapy; Hepatitis; Histocompatibility antigen HLA; Hospitals; Human Clinical; Humans; Immune response; Inflammation; Injection; Ischemia; Ischemia / Reperfusion Injury; Logistics; Male; Mesenchymal Stem Cell Transplantation - adverse effects; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells; Mesenchymal Stem Cells - cytology; Mesenchyme; Middle Aged; Myocardial Ischemia - complications; Myocardial Ischemia - therapy; Myocardium; Patient safety; Patients; Somatic cell therapy; Stem cell transplantation; Stem cells; Stromal cells; Studies; Surgery; Tissue regeneration; Transplantation, Homologous; Vascular Regeneration; Ventricle; New York; United States > US; Somatic cell therapy; Adipose stem cells; Cardiac; Stromal cells; Cellular therapy; Clinical trial; Tissue regeneration; Mesenchymal stem cells
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.17-0040

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 Production circle of allogeneic mesenchymal stromal cells from healthy donors to treatment of heart failure patients.