ArticleFrontiers in veterinary science2026
Muse-like stem cell therapy for curing chronic diseases in geriatric feline and canine.
Article in Frontiers in veterinary science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Multilineage-differentiating stress-enduring (Muse) cells, a subpopulation of mesenchymal stem cells (MSCs) marked by stage-specific embryonic antigen 3 (SSEA3), exhibit superior regenerative capacity compared to conventional MSCs, including enhanced tissue homing, pluripotency, and paracrine effects. However, their natural scarcity (1-5% in MSC populations) limits therapeutic scalability. In this study, we developed a five-compound small molecule method to obtain compound-enriched Muse-like MSCs and assessed their potential use in treating severe veterinary chronic diseases, such as hepatitis and chronic kidney disease (CKD). Methods: Umbilical cord-derived MSCs from cats and dogs were isolated and cultured, using a combination of five small molecules to obtain enriched Muse-like cells. The cultivation process was verified by immunofluorescence and flow cytometry. Differentiation potential of obtained Muse-like cells was evaluated under lineage-specific conditions. These compound-enriched Muse-like MSCs were administered intravenously (2 × 10 Results: Screening of over 100 small-molecule compounds identified optimized five-compound cocktails-valproic acid (0.5 mM), CHIR99021 (3 μM), PD0325901 (0.5 μM), Trolox (10 μM), and nicotinamide (1 mM) for feline MSCs; parnate (10 μM), CHIR99021 (3 μM), PD0325901 (0.5 μM), Trolox (10 μM), and Y27632 (10 μM) for canine MSCs. These small-molecule cocktail effectively boosted SSEA3 positivity, from 0.1-1% to approximately 40%, as confirmed by immunofluorescence staining and flow cytometry. These enriched Muse-like cells demonstrated superior stress tolerance and robust spontaneous differentiation into endodermal (KRT7 + hepatocyte-like), mesodermal (cTnI+ cardiomyocyte-like), and ectodermal (Nestin+ neural progenitor) lineages under targeted induction conditions, which were not observed in untreated MSCs. In therapeutic applications, the enriched Muse-like MSCs normalized feline liver indices by day 21 and improved canine renal markers by day 28, accompanied by notable anti-aging effects. Conclusion: A small molecule cocktail method was introduced to enhance the Muse population in MSCs, which provide a safe and effective way to harvest Muse cells. These Muse-like MSCs demonstrate high clinical potential for chronic and age-related degenerative diseases, making it a safe and effective therapeutic option.
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