Automated Large-Scale Production of Paclitaxel Loaded Mesenchymal Stromal Cells for Cell Therapy Applications

Mesenchymal stromal cells (MSCs) prepared as advanced therapies medicinal products (ATMPs) have been widely used for the treatment of different diseases. The latest developments concern the possibility to use MSCs as carrier of molecules, including chemotherapeutic drugs. Taking advantage of their intrinsic homing feature, MSCs may improve drugs localization in the disease area. However, for cell therapy applications, a significant number of MSCs loaded with the drug is required. We here investigate the possibility to produce a large amount of Good Manufacturing Practice (GMP)-compliant MSCs loaded with the chemotherapeutic drug Paclitaxel (MSCs-PTX), using a closed bioreactor system. Cells were obtained starting from 13 adipose tissue lipoaspirates. All samples were characterized in terms of number/viability, morphology, growth kinetics, and immunophenotype. The ability of MSCs to internalize PTX as well as the antiproliferative activity of the MSCs-PTX in vitro was also assessed. The results demonstrate that our approach allows a large scale expansion of cells within a week; the MSCs-PTX, despite a different morphology from MSCs, displayed the typical features of MSCs in terms of viability, adhesion capacity, and phenotype. In addition, MSCs showed the ability to internalize PTX and finally to kill cancer cells, inhibiting the proliferation of tumor lines in vitro. In summary our results demonstrate for the first time that it is possible to obtain, in a short time, large amounts of MSCs loaded with PTX to be used in clinical trials for the treatment of patients with oncological diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Pharmaceutics - 12(2020), 5 vom: 30. Apr.

Sprache:

Englisch

Beteiligte Personen:

Lisini, Daniela [VerfasserIn]
Nava, Sara [VerfasserIn]
Frigerio, Simona [VerfasserIn]
Pogliani, Simona [VerfasserIn]
Maronati, Guido [VerfasserIn]
Marcianti, Angela [VerfasserIn]
Coccè, Valentina [VerfasserIn]
Bondiolotti, Gianpietro [VerfasserIn]
Cavicchini, Loredana [VerfasserIn]
Paino, Francesca [VerfasserIn]
Petrella, Francesco [VerfasserIn]
Alessandri, Giulio [VerfasserIn]
Parati, Eugenio A [VerfasserIn]
Pessina, Augusto [VerfasserIn]

Links:

Volltext

Themen:

Cell expansion
Cell therapy
GMPs
Journal Article
MSCs
Paclitaxel

Anmerkungen:

Date Revised 28.09.2020

published: Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.3390/pharmaceutics12050411

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM309494249