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BioMed Research International
Volume 2015 (2015), Article ID 473159, 10 pages
http://dx.doi.org/10.1155/2015/473159
Research Article

Full GMP-Compliant Validation of Bone Marrow-Derived Human CD133+ Cells as Advanced Therapy Medicinal Product for Refractory Ischemic Cardiomyopathy

1Laboratory of Cell Therapy “Stefano Verri”, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy
2Department of Health Science, Università degli Studi di Milano-Bicocca, piazza dell’Ateneo Nuovo 1, 20126 Milan, Italy
3Tettamanti Research Center, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy
4Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy
5Department of Pediatrics, MBBM Foundation, Ospedale San Gerardo, Via Pergolesi 33, 20900 Monza, Italy
6Department of Ematology, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy
7Department of Cardiovascular Surgery, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy
8Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy

Received 19 March 2015; Accepted 11 May 2015

Academic Editor: Sebastiano Sciarretta

Copyright © 2015 Daniela Belotti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+ cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 106 of CD133+ cells (range 2.85 × 106–30.84 × 106), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133+ cells of 90,60% (range 81,40%–96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106 cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).