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Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use

1
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
2
Department of Veterinary Medical Science, University of Parma, 43121 Parma, Italy
3
Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna, 25124 Brescia, Italy
4
Institute of Biomedical Technologies, F.lli Cervi 93, 20054 Segrate, Italy
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Freelance Veterinary Medical Doctor, 43121 Parma, Italy
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Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2/3, 28100 Novara, Italy
7
PharmaExceed S.r.l., Piazza Castello, 19, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Equally contributed to the paper.
Academic Editor: Nuno A. Silva
Pharmaceuticals 2021, 14(6), 553; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060553
Received: 30 April 2021 / Revised: 31 May 2021 / Accepted: 8 June 2021 / Published: 10 June 2021
In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility for veterinary clinical-use medicinal production. Critical parameters for quality control and batch release have been identified regarding (i) physicochemical properties; (ii) extracellular vesicle morphology, size distribution, and surface biomarker; (iii) protein and lipid content; (iv) requirements for injectable pharmaceutical dosage forms such as sterility, bacterial endotoxin, and Mycoplasma; and (v) in vitro potency tests, as anti-elastase activity and proliferative activity on musculoskeletal cell lines (tenocytes and chondrocytes) and mesenchymal stromal cells. Finally, proteins putatively responsible for the biological effects have been identified by Lyosecretome proteomic investigation: IL10RA, MXRA5, RARRES2, and ANXA1 modulate the inflammatory process RARRES2, NOD1, SERPINE1, and SERPINB9 with antibacterial activity. The work provides a proof-of-concept for the manufacturing of clinical-grade equine freeze-dried secretome, and prototypes are now available for safety and efficacy clinical trials in the treatment of equine musculoskeletal diseases View Full-Text
Keywords: mesenchymal stem cells; secretome; regenerative medicine; musculoskeletal disorders; equine mesenchymal stem cells; secretome; regenerative medicine; musculoskeletal disorders; equine
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MDPI and ACS Style

Mocchi, M.; Grolli, S.; Dotti, S.; Di Silvestre, D.; Villa, R.; Berni, P.; Conti, V.; Passignani, G.; Brambilla, F.; Bue, M.D.; Catenacci, L.; Sorrenti, M.; Segale, L.; Bari, E.; Mauri, P.; Torre, M.L.; Perteghella, S. Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use. Pharmaceuticals 2021, 14, 553. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060553

AMA Style

Mocchi M, Grolli S, Dotti S, Di Silvestre D, Villa R, Berni P, Conti V, Passignani G, Brambilla F, Bue MD, Catenacci L, Sorrenti M, Segale L, Bari E, Mauri P, Torre ML, Perteghella S. Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use. Pharmaceuticals. 2021; 14(6):553. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060553

Chicago/Turabian Style

Mocchi, Michela, Stefano Grolli, Silvia Dotti, Dario Di Silvestre, Riccardo Villa, Priscilla Berni, Virna Conti, Giulia Passignani, Francesca Brambilla, Maurizio D. Bue, Laura Catenacci, Milena Sorrenti, Lorena Segale, Elia Bari, Pierluigi Mauri, Maria L. Torre, and Sara Perteghella. 2021. "Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use" Pharmaceuticals 14, no. 6: 553. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060553

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