Full GMP-compliant validation of bone marrow-derived human CD133(+) cells as advanced therapy medicinal product for refractory ischemic cardiomyopathy.
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 × 10(6) of CD133(+) cells (range 2.85 × 10(6)-30.84 × 10(6)), 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 × 10(6) cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).
Laboratory of Cell Therapy "Stefano Verri", Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy ; Department of Health Science, Università degli Studi di Milano-Bicocca, piazza dell'Ateneo Nuovo 1, 20126 Milan, Italy.
Daniela
D
Belotti
Laboratory of Cell Therapy "Stefano Verri", Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy ; Tettamanti Research Center, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy.
Giuseppe
G
Gaipa
Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy.
Beatrice
B
Bassetti
Laboratory of Cell Therapy "Stefano Verri", Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy ; Tettamanti Research Center, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy.
Benedetta
B
Cabiati
Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy.
Gabriella
G
Spaltro
Laboratory of Cell Therapy "Stefano Verri", Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy ; Department of Health Science, Università degli Studi di Milano-Bicocca, piazza dell'Ateneo Nuovo 1, 20126 Milan, Italy ; Tettamanti Research Center, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy ; Department of Pediatrics, MBBM Foundation, Ospedale San Gerardo, Via Pergolesi 33, 20900 Monza, Italy.
Ettore
E
Biagi
Department of Ematology, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy.
Matteo
M
Parma
Department of Health Science, Università degli Studi di Milano-Bicocca, piazza dell'Ateneo Nuovo 1, 20126 Milan, Italy ; Tettamanti Research Center, Azienda Ospedaliera San Gerardo, Via Pergolesi 33, 20900 Monza, Italy ; Department of Pediatrics, MBBM Foundation, Ospedale San Gerardo, Via Pergolesi 33, 20900 Monza, Italy.
Andrea
A
Biondi
Department of Cardiovascular Surgery, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy.
Laura
L
Cavallotti
Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy.
Elisa
E
Gambini
Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy ; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy.
Giulio
G
Pompilio
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000592:standards*; D009202:Cardiomyopathies / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D018795:Device Approval / Q000592:standards; D005060:Europe; D006023:Glycoproteins / Q000378:metabolism*; D019983:Guideline Adherence; D006801:Humans; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000378:metabolism*; D017410:Practice Guidelines as Topic; D033581:Stem Cell Transplantation / Q000592:standards*; D013234:Stem Cells
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides