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Stem cells (Dayton, Ohio)2024; 42(8); 677-705; doi: 10.1093/stmcls/sxae034

Evaluation of stem-cell therapies in companion animal disease models: a concise review (2015-2023).

Abstract: Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The majority of studies were performed in dogs (n = 28), with additional studies in horses (n = 9) and cats (n = 8). Disease models included those related to musculoskeletal disease (osteoarthritis and tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune-mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy), and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies are needed. Enhanced understanding of the temporal course of disease processes using advanced-omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem-cell-based therapies could include use of stem-cell-derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness.
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Publication Date: 2024-05-25 PubMed ID: 38795363PubMed Central: PMC13032169DOI: 10.1093/stmcls/sxae034Google Scholar: Lookup
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  • Journal Article
  • Review
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This research article provides an updated review of studies from 2015 to 2023 investigating stem cell therapies in naturally occurring diseases of companion animals (dogs, cats, and horses) that model human diseases.
  • The review assesses the safety, efficacy, and potential of stem cell treatments across a range of conditions, highlighting progress since a previous 2008-2015 review and identifying areas needing further research and regulatory improvement.

Study Inclusion and Scope

  • The review focused on stem cell therapy studies in companion animals affected by spontaneous diseases, excluding:
    • Case reports and experimental disease models
    • Research involving cancer
    • Studies on purpose-bred laboratory animals like rodents
  • The authors identified 45 relevant studies published between 2015 and 2023, more than doubling the 19 studies covered in their previous review (2008–2015).
  • Species breakdown:
    • Dogs: 28 studies
    • Horses: 9 studies
    • Cats: 8 studies

Types of Diseases Studied

  • Musculoskeletal diseases:
    • Osteoarthritis
    • Tendon and ligament injuries
  • Neurologic diseases:
    • Canine cognitive dysfunction
    • Intervertebral disc disease
    • Spinal cord injury
  • Gingival/dental disease:
    • Gingivostomatitis
  • Dermatologic disease:
    • Atopic dermatitis
  • Chronic multi-drug resistant infections
  • Ophthalmic diseases:
    • Keratoconjunctivitis sicca
    • Eosinophilic keratitis
    • Immune-mediated keratitis
  • Cardiopulmonary diseases:
    • Asthma
    • Degenerative valve disease
    • Dilated cardiomyopathy
  • Gastrointestinal diseases:
    • Inflammatory bowel disease
    • Chronic enteropathy
  • Renal disease:
    • Chronic kidney disease

Key Findings on Efficacy and Study Design

  • The majority of studies reported beneficial effects of stem cell therapy across various disease models.
  • Exceptions were noted for chronic and severe conditions such as:
    • Spinal cord injury
    • Chronic kidney disease
  • Study quality and design varied:
    • 22 studies were open-label, baseline-controlled trials with no blinding or placebo control.
    • Only 12 studies were randomized and controlled, which are considered more rigorous.
    • This variability complicates interpretation of efficacy and safety results.

Challenges and Recommendations

  • Regulatory Issues:
    • More robust regulatory oversight of stem cell therapy manufacturing and clinical use is needed.
  • Consistency:
    • Standardization in stem cell product production is necessary to ensure reproducibility and safety.
  • Understanding Disease Mechanisms:
    • Advanced “omics” technologies (e.g., genomics, proteomics) could clarify the timing and mechanism of stem cell effects relative to disease progression.

Future Directions

  • Exploration of stem cell-derived extracellular vesicles as an alternative to whole-cell therapies, potentially offering targeted effects with reduced risks.
  • Development of cell-conditioning techniques to guide stem cells toward specific repair or immunomodulatory pathways, tailored to individual disease types and stages.
  • Greater emphasis on designing well-controlled, randomized trials to improve the evidence base for clinical decision-making.

Cite This Article

APA
Williams ZJ, Pezzanite LM, Chow L, Rockow M, Dow SW. (2024). Evaluation of stem-cell therapies in companion animal disease models: a concise review (2015-2023). Stem Cells, 42(8), 677-705. https://doi.org/10.1093/stmcls/sxae034

Publication

Stem cells (Dayton, Ohio)
ISSN: 1549-4918
NlmUniqueID: 9304532
Country: England
Language: English
Volume: 42
Issue: 8
Pages: 677-705

Researcher Affiliations

Williams, Zoë J
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Pezzanite, Lynn M
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Chow, Lyndah
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Rockow, Meagan
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Dow, Steven W
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.

MeSH Terms

  • Animals
  • Stem Cell Transplantation / methods
  • Disease Models, Animal
  • Dogs
  • Humans
  • Pets
  • Cats
  • Cell- and Tissue-Based Therapy / methods

Grant Funding

  • T32 TR004366 / NCATS NIH HHS

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors acknowledge that they hold stock options in eQCell Inc. (L.P., S.D.), Validus Cellular Therapeutics (S.D.), and have filed provisional patents and have issued patents covering immune activated MSC technology for treatment of chronic infections (S.D.) and musculoskeletal diseases (S.D., L.P., L.C.).

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