Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs

In recent years, mesenchymal stromal cells (MSCs) have shown promise as a therapy in treating musculoskeletal diseases, and it is currently believed that their therapeutic effect is mainly related to the release of proteins and extracellular vesicles (EVs), known as secretome. In this work, three ba...

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Autores principales:	Michela Mocchi, Elia Bari, Silvia Dotti, Riccardo Villa, Priscilla Berni, Virna Conti, Maurizio Del Bue, Gian Paolo Squassino, Lorena Segale, Roberto Ramoni, Maria Luisa Torre, Sara Perteghella, Stefano Grolli
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mesenchymal stem/stromal cells MSC-secretome canine regenerative medicine osteoarthritis Veterinary medicine SF600-1100 Zoology QL1-991
Acceso en línea:	https://doaj.org/article/25d59ebfdf3a462690f7510e90f76483
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spelling	oai:doaj.org-article:25d59ebfdf3a462690f7510e90f764832021-11-25T16:20:10ZCanine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs10.3390/ani111132712076-2615https://doaj.org/article/25d59ebfdf3a462690f7510e90f764832021-11-01T00:00:00Zhttps://www.mdpi.com/2076-2615/11/11/3271https://doaj.org/toc/2076-2615In recent years, mesenchymal stromal cells (MSCs) have shown promise as a therapy in treating musculoskeletal diseases, and it is currently believed that their therapeutic effect is mainly related to the release of proteins and extracellular vesicles (EVs), known as secretome. In this work, three batches of canine MSC-secretome were prepared by standardized processes according to the current standard ISO9001 and formulated as a freeze-dried powder named Lyosecretome. The final products were characterized in protein and lipid content, EV size distribution and tested to ensure the microbiological safety required for intraarticular injection. Lyosecretome induced the proliferation of adipose tissue-derived canine MSCs, tenocytes, and chondrocytes in a dose-dependent manner and showed anti-elastase activity, reaching 85% of inhibitory activity at a 20 mg/mL concentration. Finally, to evaluate the safety of the preparation, three patients affected by bilateral knee or elbow osteoarthritis were treated with two intra-articular injections (t = 0 and t = 40 days) of the allogeneic Lyosecretome (20 mg corresponding 2 × 10<sup>6</sup> cell equivalents) resuspended in hyaluronic acid in one joint and placebo (mannitol resuspended in hyaluronic acid) in the other joint. To establish the safety of the treatment, the follow-up included a questionnaire addressed to the owner and orthopaedic examinations to assess lameness grade, pain score, functional disability score and range of motion up to day 80 post-treatment. Overall, the collected data suggest that intra-articular injection of allogeneic Lyosecretome is safe and does not induce a clinically significant local or systemic adverse response.Michela MocchiElia BariSilvia DottiRiccardo VillaPriscilla BerniVirna ContiMaurizio Del BueGian Paolo SquassinoLorena SegaleRoberto RamoniMaria Luisa TorreSara PerteghellaStefano GrolliMDPI AGarticlemesenchymal stem/stromal cellsMSC-secretomecanine regenerative medicineosteoarthritisVeterinary medicineSF600-1100ZoologyQL1-991ENAnimals, Vol 11, Iss 3271, p 3271 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mesenchymal stem/stromal cells MSC-secretome canine regenerative medicine osteoarthritis Veterinary medicine SF600-1100 Zoology QL1-991
spellingShingle	mesenchymal stem/stromal cells MSC-secretome canine regenerative medicine osteoarthritis Veterinary medicine SF600-1100 Zoology QL1-991 Michela Mocchi Elia Bari Silvia Dotti Riccardo Villa Priscilla Berni Virna Conti Maurizio Del Bue Gian Paolo Squassino Lorena Segale Roberto Ramoni Maria Luisa Torre Sara Perteghella Stefano Grolli Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs
description	In recent years, mesenchymal stromal cells (MSCs) have shown promise as a therapy in treating musculoskeletal diseases, and it is currently believed that their therapeutic effect is mainly related to the release of proteins and extracellular vesicles (EVs), known as secretome. In this work, three batches of canine MSC-secretome were prepared by standardized processes according to the current standard ISO9001 and formulated as a freeze-dried powder named Lyosecretome. The final products were characterized in protein and lipid content, EV size distribution and tested to ensure the microbiological safety required for intraarticular injection. Lyosecretome induced the proliferation of adipose tissue-derived canine MSCs, tenocytes, and chondrocytes in a dose-dependent manner and showed anti-elastase activity, reaching 85% of inhibitory activity at a 20 mg/mL concentration. Finally, to evaluate the safety of the preparation, three patients affected by bilateral knee or elbow osteoarthritis were treated with two intra-articular injections (t = 0 and t = 40 days) of the allogeneic Lyosecretome (20 mg corresponding 2 × 10<sup>6</sup> cell equivalents) resuspended in hyaluronic acid in one joint and placebo (mannitol resuspended in hyaluronic acid) in the other joint. To establish the safety of the treatment, the follow-up included a questionnaire addressed to the owner and orthopaedic examinations to assess lameness grade, pain score, functional disability score and range of motion up to day 80 post-treatment. Overall, the collected data suggest that intra-articular injection of allogeneic Lyosecretome is safe and does not induce a clinically significant local or systemic adverse response.
format	article
author	Michela Mocchi Elia Bari Silvia Dotti Riccardo Villa Priscilla Berni Virna Conti Maurizio Del Bue Gian Paolo Squassino Lorena Segale Roberto Ramoni Maria Luisa Torre Sara Perteghella Stefano Grolli
author_facet	Michela Mocchi Elia Bari Silvia Dotti Riccardo Villa Priscilla Berni Virna Conti Maurizio Del Bue Gian Paolo Squassino Lorena Segale Roberto Ramoni Maria Luisa Torre Sara Perteghella Stefano Grolli
author_sort	Michela Mocchi
title	Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs
title_short	Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs
title_full	Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs
title_fullStr	Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs
title_full_unstemmed	Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs
title_sort	canine mesenchymal cell lyosecretome production and safety evaluation after allogenic intraarticular injection in osteoarthritic dogs
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/25d59ebfdf3a462690f7510e90f76483
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Canine Mesenchymal Cell Lyosecretome Production and Safety Evaluation after Allogenic Intraarticular Injection in Osteoarthritic Dogs

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