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International journal of pharmaceutics2025; 681; 125864; doi: 10.1016/j.ijpharm.2025.125864

Clinical evaluation of freeze-dried secretome (lyosecretome) for osteoarthritis: a controlled trial in dogs and preliminary safety assessment in horses.

Abstract: Most in vivo studies on MSC-secretome for osteoarthritis (OA) have relied on animal models, using products lacking pharmaceutical quality, not formulated for clinical use, and insufficiently characterized, limiting knowledge of its effectiveness. This study reports veterinary clinical trials on dogs and horses with spontaneous OA: in dogs (26 subjects), the trial is randomized, double-blinded, and controlled; in horses, 5 clinical cases were treated for safety assessment. Treatment consisted of hyaluronic acid with either lyosecretome - a freeze-dried, injectable MSC-secretome obtained through standardized GMP manufacturing - or mannitol, the lyosecretome excipient (control), intrarticularly administered. Patients underwent clinical evaluations and orthopedic assessments over an 80-day follow-up; dog-owner feedback was collected through questionnaires. Lyosecretome doesn't induce systemic adverse responses. In dogs, improvement following treatment - significant in favor of lyosecretome - was observed, especially in reducing lameness; although it did not demonstrate significant pain reduction, patients were significantly more likely to walk, play, and move easily after exercise. Proteomic investigation supported these efficacy findings, revealing lyosecretome proteins involved in inhibiting protease and hyaluronidase, as well as in regulating immune response and inflammation, and those associated with cartilage regeneration and antioxidant activity. These results support the beneficial effect of MSC-secretome on joint disorders and offer insights that may be relevant to human patients, given the similarities in OA pathophysiology between humans and dogs or horses.
Publication Date: 2025-06-16 PubMed ID: 40532750DOI: 10.1016/j.ijpharm.2025.125864Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

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The research article examines the effectiveness of a freeze-dried injectable product derived from mesenchymal stem cells (lyosecretome) in treating osteoarthritis in dogs and horses. In dogs, it showed significant improvement in reducing lameness and increased mobility post-exercise, while the proteomic investigation substantiated its effectiveness in inhibiting damaging enzymes and regulating immune response.

Study Participants and Methodology

  • The study was conducted on 26 dogs and five horses suffering from spontaneous osteoarthritis. The trial with dogs was randomized, double-blinded, and controlled, ensuring unbiased results, whereas the horses were part of a preliminary safety assessment.
  • The treatment administered consisted of hyaluronic acid, either in combination with lyosecretome or mannitol (serving as a control), injected into the joint.
  • Clinical evaluations and orthopedic assessments were performed over an 80-day follow-up period, and subjective observations were collected from dog owners through questionnaires.

Treatment Outcomes

  • Lyosecretome did not induce any systemic adverse responses in the tested animals, upholding its safety profile.
  • In dogs, there was a significant improvement observed post-treatment, particularly evident in reducing lameness. Even though there was no significant reduction in pain, treated dogs were more likely to engage in activities like walking, playing, and moving more easily after exercise.

Proteomic Investigation

  • In order to better understand the underlying mechanisms supporting the observed fitness and mobility improvements, a proteomic analysis was conducted.
  • This analysis revealed that lyosecretome contains proteins that inhibit protease and hyaluronidase, enzymes that contribute to the breakdown of cartilage – a key symptom of osteoarthritis.
  • The proteins in lyosecretome help regulate the immune response and inflammation, which are also crucial in managing osteoarthritis. Furthermore, proteins associated with cartilage regeneration and antioxidant activity were identified, signifying its potential in enhancing joint health.

Significance of the Findings

  • The study provides compelling evidence on the potential positive effects of lyosecretome on osteoarthritis, owing to the substantial improvement witnessed in the health and mobility of the treated dogs.
  • The proteomic investigation provides an understanding of the potential mechanisms through which lyosecretome achieves its therapeutic outcomes.
  • Considering the similarities in osteoarthritis pathophysiology among dogs, horses, and humans, the outcomes of this study may carry significant implications for human osteoarthritis treatment as well.

Cite This Article

APA
Berni P, Del Bue M, Conti V, Andreoli V, Ramoni R, Angelone M, Squassino GP, Bari E, Torre ML, Rinaldi M, Dotti S, Rossi R, Yusuf I, Mauri P, Di Silvestre D, Grolli S. (2025). Clinical evaluation of freeze-dried secretome (lyosecretome) for osteoarthritis: a controlled trial in dogs and preliminary safety assessment in horses. Int J Pharm, 681, 125864. https://doi.org/10.1016/j.ijpharm.2025.125864

Publication

ISSN: 1873-3476
NlmUniqueID: 7804127
Country: Netherlands
Language: English
Volume: 681
Pages: 125864

Researcher Affiliations

Berni, Priscilla
  • Department of Veterinary Sciences, University of Parma, Via del Taglio 10, 43126 Parma, Italy.
Del Bue, Maurizio
  • Freelance Veterinary Medical Doctor, 43121 Parma, Italy.
Conti, Virna
  • Department of Veterinary Sciences, University of Parma, Via del Taglio 10, 43126 Parma, Italy.
Andreoli, Valentina
  • Department of Veterinary Sciences, University of Parma, Via del Taglio 10, 43126 Parma, Italy.
Ramoni, Roberto
  • Department of Veterinary Sciences, University of Parma, Via del Taglio 10, 43126 Parma, Italy.
Angelone, Mario
  • Department of Veterinary Sciences, University of Parma, Via del Taglio 10, 43126 Parma, Italy.
Squassino, Gian Paolo
  • Veterinary Practitioner, Studio Tecnico Veterinario, Via Alfredo Catalani 12/14, 14100 Asti, Italy.
Bari, Elia
  • Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy. Electronic address: elia.bari@uniupo.it.
Torre, Maria Luisa
  • Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.
Rinaldi, Maurizio
  • Department of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.
Dotti, Silvia
  • Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Via Antonio Bianchi 9, 25124 Brescia, Italy.
Rossi, Rossana
  • Institute for Biomedical Technologies - National Research Council, Via Fratelli Cervi 93, 20054 Segrate, Italy.
Yusuf, Ishak
  • Institute for Biomedical Technologies - National Research Council, Via Fratelli Cervi 93, 20054 Segrate, Italy.
Mauri, Pierluigi
  • Institute for Biomedical Technologies - National Research Council, Via Fratelli Cervi 93, 20054 Segrate, Italy.
Di Silvestre, Dario
  • Institute for Biomedical Technologies - National Research Council, Via Fratelli Cervi 93, 20054 Segrate, Italy.
Grolli, Stefano
  • Department of Veterinary Sciences, University of Parma, Via del Taglio 10, 43126 Parma, Italy.

MeSH Terms

  • Animals
  • Dogs
  • Female
  • Male
  • Dog Diseases / drug therapy
  • Double-Blind Method
  • Freeze Drying
  • Horse Diseases / drug therapy
  • Horses
  • Hyaluronic Acid / administration & dosage
  • Injections, Intra-Articular
  • Osteoarthritis / veterinary
  • Osteoarthritis / drug therapy
  • Secretome

Conflict of Interest Statement

Declaration of competing interest Maria Luisa Torre is a co-founder and member of the advisory board of the company PharmaExceed s.r.l.