Allogeneic Mesenchymal Stem Cell Transplantation in Dogs with Keratoconjunctivitis Sicca

Abstract

Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild-moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 10 6 ) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short-and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short-and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild-moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration.

Bone marrow stem cell applied in the canine veterinary clinics

“…In dogs, the presence of HSCs have been observed mostly in bone marrow and umbilical cord blood, being used in cell therapy for neoplasia, hematological, metabolic, and immunological diseases (Bruno et al 2009, Nakage et al 2009, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”

“…Additionally, several studies demonstrated, the regenerative function of these cells in damaged tissues (Narazaki & Cristante 2011, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”

“…On the other hand, mesenchymal stem cell from BMSC can be used in the veterinary clinic for example, in the treatment of bone fractures, spinal cord damage and dermatitis (Pereira et al 2008, Bydlowski et al 2009, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016). Thus, this study aimed to carry out a short-review about bone marrow stem cell and check their applicability in the treatment of various diseases in the canine.…”

“…(Friedenstein et al 1974, Tharasanit et al 2011, Rici et al 2012, Kim et al 2013, Hu et al 2014 postnatal life, is the most studied, having two lines of stem cells: hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) (Bittencourt et al 2006, BydlowskI et al 2009, Narazaki & Cristante 2011 (Fig.1 and 2). Furthermore, BMSC is the main source of stem cells, because of its easy isolation, and more than one to six millions of mesenchymal or/and hematopoietic stem cell can be isolated, cultured and applied without problem from one isolation (Oliveira et al 2010, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”

“…The aspiration usually occurs in the epiphysis of long bones, such as the greater trochanter of the femur and greater tuberosity of the humeral bone, iliac crest and trans-iliac area in vivo. In dogs, the region of the iliac crest is widely used due to its location within easy reach (Raskin 1998, Ryu et al 2012, Bittencourt et al 2016, Stolfi et al 2016.…”