Abstract
Mesenchymal stem cells (MSCs) have emerged as a new therapy for various immune-mediated inflammatory diseases. In this study we perform the first double-blinded, placebo-controlled evaluation of the efficacy of adipose-derived allogenic canine MSCs for the treatment of canine atopic dermatitis (cAD). Enrolled canine patients were randomly divided into placebo (PBS saline), low-dose (5 × 105 cells/kg), and high-dose (5 × 106 cells/kg) treatment groups. Each patient received three subcutaneous MSCs treatments or PBS saline at four-week intervals with injections at five sites. Patients were monitored by physical exams, pruritus visual analog scales (PVAS) signed by the primary caretaker, canine atopic dermatitis extent and severity index-4 (CADESI-4) scores by two veterinarians, and complete blood count and serum chemistry analysis along with laboratory analysis for potential biomarkers. Patients were kept off any immune-modulating drugs during the study period, and oral antibiotics and topicals were used for managing pruritus and secondary infections. The PVAS scores and the serum miR-483 levels were significantly lower in the high dose group compared to the placebo group at day90 post first-treatment. The CADESI-4 scores of the high dose group also showed downward trends. No severe adverse effects were observed in any patient in this study. The high dose MSC treatment is efficacious in alleviating the clinical signs of cAD until 30 days after the last subcutaneous administration of MSCs, and miRNA-483 may be a reliable prognostic biomarker for cAD. The MSCs efficacy and potential biomarkers should be further explored by a larger scale clinical trial.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request, while strictly maintaining patient and client confidentiality.
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Funding
This work was supported by the grant from PrimeGen US to Gagandeep Kaur and Jijun Hao and by the intramural grant from Western University of Health Sciences to Jijun Hao. Chad Maki and Fari Izadyar were, and Tom Ramos is the employee/s of PrimeGen US and received funding in the form of salaries during this study. The specific roles of these authors are articulated in the ‘Author Contributions’. The funders provided support in the form of study reagents and were involved in study design and preparation of the manuscript.
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The study conception and design were planned by Chad Maki, Charli Dong, David Clark, Fari Izadyar, Gagandeep Kaur, Jijun Hao and Tom Ramos. Clinical and laboratory experiments were performed by Ana Ramirez, Chen Xie, David Clark, Gagandeep Kaur, Jerry Harb, and Jijun Hao. Data analysis was performed by Ana Ramirez, Gagandeep Kaur, Jijun Hao, and Sandy Najera. Gagandeep Kaur, Jijun Hao, and Tom Ramos drafted the manuscript and all authors commented on previous versions. All authors read and approved the final manuscript.
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This study complies with institutional guidelines on the use of animals in clinical research and was approved by the Institutional Animal Care and Use Committee (IACUC) of Western University of Health Sciences (Pomona, CA, USA). All enrolled dogs were client-owned patients of the Pet Health Center at the Western University of Health Sciences.
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Informed owner consent form was obtained from the primary caretaker or owner of all the dogs enrolled in the study.
Competing interests
This work was supported by the grant from PrimeGen US to Gagandeep Kaur and Jijun Hao and by the intramural grant from Western University of Health Sciences to Jijun Hao. Chad Maki and Fari Izadyar were, and Tom Ramos is the employee/s of PrimeGen US and received funding in the form of salaries during this study. This does not alter our adherence to journal’s policies on sharing data and materials. A provisional patent application based on this data has been submitted by PrimeGen US.
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Kaur, G., Ramirez, A., Xie, C. et al. A double-blinded placebo-controlled evaluation of adipose-derived mesenchymal stem cells in treatment of canine atopic dermatitis. Vet Res Commun 46, 251–260 (2022). https://doi.org/10.1007/s11259-021-09853-9
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DOI: https://doi.org/10.1007/s11259-021-09853-9