Topical applications of allogeneic adipose-derived mesenchymal stem cells ameliorate the canine keratoconjunctivitis sicca

Li-Ning Wei; Ching-Ho Wu; Chung-Tien Lin; I-Hsuan Liu

doi:10.1186/s12917-022-03303-7

Topical applications of allogeneic adipose-derived mesenchymal stem cells ameliorate the canine keratoconjunctivitis sicca

BMC Vet Res. 2022 Jun 10;18(1):217. doi: 10.1186/s12917-022-03303-7.

Authors

Li-Ning Wei^{1

2}, Ching-Ho Wu^{1

3}, Chung-Tien Lin^{4

5}, I-Hsuan Liu^{6

7}

Affiliations

¹ Institute of Veterinary Clinical Sciences, School of Veterinary Medicine, National Taiwan University, Taipei, 106, Taiwan.
² Department of Ophthalmology, National Taiwan University Veterinary Hospital, Taipei, 106, Taiwan.
³ Department of Small Animal Surgery, National Taiwan University Veterinary Hospital, Taipei, 106, Taiwan.
⁴ Institute of Veterinary Clinical Sciences, School of Veterinary Medicine, National Taiwan University, Taipei, 106, Taiwan. ctlin@ntu.edu.tw.
⁵ Department of Ophthalmology, National Taiwan University Veterinary Hospital, Taipei, 106, Taiwan. ctlin@ntu.edu.tw.
⁶ Department of Animal Science and Technology, National Taiwan University, Taipei, 106, Taiwan. ihliu@ntu.edu.tw.
⁷ Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 106, Taiwan. ihliu@ntu.edu.tw.

Abstract

Background: Canine keratoconjunctivitis sicca (KCS) is predominantly an immune-mediated disease. Current therapy of canine KCS is mainly by immunosuppressant, but the effectiveness was limited in some patients. In the past few years, some studies showed the results of the use of mesenchymal stem cells in treating canine KCS via periocular injections. However, the periocular injection procedure requires sedation or general anesthesia, and may lead to iatrogenic or incidental injury during the injection process. The aim of this study was to investigate the efficacy of topical allogenic canine adipose-derived mesenchymal stem cells (cAD-MSCs) in clinical patients of canine KCS.

Results: The cAD-MSCs used in this study were characterized for their capability of tri-lineage differentiation and immunomodulatory properties. In addition, preparation methods for eye drops of cAD-MSCs was developed and its optimal preservation was tested. The canine KCS patients were recruited for clinical trial and divided into two groups based on their history of previous treatment. All patients received topical cAD-MSCs treatment once per week for 6 consecutive weeks and complete ophthalmic examinations were performed 1 week before treatment (week 0) and at 3rd, 6th, 9th weeks, respectively. The results showed that the quantity and quality of tears have improved significantly following topical cAD-MSCs treatment based on Schirmers tear test-1 and tear break-up time. More than half of all patients were found improved in the tear quantity. In particular, 56.5% of the patients that were unresponsive to prior immunosuppressant therapy had an effective increase in tear volume. The severity of clinical signs was also ameliorated according to the numeric rating scale score from both patient owners and the clinician.

Conclusion: To sum up, topical cAD-MSCs may be beneficial especially in KCS patients with poor owner compliance for frequent daily use of eye drops or those who are unresponsive to immunosuppressant therapy.

Keywords: Adipose-Derived Mesenchymal Stem Cells; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Ophthalmic Administration.

MeSH terms

Animals
Dog Diseases* / drug therapy
Dogs
Hematopoietic Stem Cell Transplantation* / veterinary
Immunosuppressive Agents / therapeutic use
Keratoconjunctivitis Sicca* / drug therapy
Keratoconjunctivitis Sicca* / veterinary
Mesenchymal Stem Cells*
Ophthalmic Solutions / therapeutic use
Tears

Substances

Immunosuppressive Agents
Ophthalmic Solutions