VETERINARY CLINICAL INVESTIGATIONS: USE OF HETEROLOGOUS MESENCHYMAL STEM CELLS IN DOGS WITH KERATOCONJUNCTIVITIS SICCA

Abstract

Purpose: To evaluate the use of heterologous mesenchymal stem cells (MSC) derived from adipose tissue in dogs with keratoconjunctivitis sicca (KSC).

Methods: MSCs were obtained under good manufacturing practice conditions and fully characterized. KSC was defined by quantitative Schirmer tear test (STT) below 15mm/min. Eleven dogs of different gender, age and race were enrolled in present study. One eye of each dog was treated with 10⁶ MSCs which were administrated in a total dose of 0.5ml of physiologic solution. Each dose was applied into two sites: 0.3 ml of MSC solution was administered directly to the main lacrimal gland and 0.2 ml to the third eyelid gland. The eyes were evaluated weekly during 8 weeks using STT, fluorescein test and slit-lamp biomicroscopy. The severity of eye score (SES) was evaluated according to conjunctival hyperemia, ocular discharge, corneal opacity or irregularity and neovascularization. Dogs, which did not show significant improvement five weeks after MSCs application, were submitted to a second application following the same protocol and scheme of evaluation.

Results: After 3 weeks the dogs showed increased STT values when compared at baseline levels and were statistically significant (p = 0.0023) This increase of STT values remained significant until the 5th week of MSM application and 55% of the dogs showed improvement in tear production with STT measurements above 15 mm/min. The remaining animals, which needed to receive two applications of MCSs, reached their peak of tear production at the 7th week, demonstrating statistically significant results as well (p = 0.003). After 8 weeks the dogs showed STT values increased, when compared with STT at the beginning of treatment (p = 0.0228). The clinical improvements of corneal opacity (p = 0.006) and conjunctival secretion (p = 0.0376) in eyes were also observed. However, the data obtained regarding the degree of conjunctival hyperemia and corneal vascularization were not statistically significant.

Conclusions: MSCs used in present study suggested their safety, once none of the animals demonstrated any type of rejection, allergic reaction or tumor formation. These cells demonstrated a clear clinical benefit in the treatment of KSC, thus improving the function of the lacrimal glands and of several other parameters. This study provides a basis for future clinical studies in humans with KSC.

Keywords: 721 stem cells • 486 cornea: tears/tear film/dry eye • 576 lacrimal gland