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Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model.

Villatoro AJ, Fernández V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA - Biomed Res Int (2015)

Bottom Line: Average STT values and all clinical signs showed a statistically significant change (P < 0.001) during the follow-up with reduction in all ocular parameters scored: ocular discharge, conjunctival hyperaemia, and corneal changes, and there were no signs of regression or worsening.Implanted cells were well tolerated and were effective reducing clinical signs of KCS with a sustained effect during the study period.These results could reinforce a good effective solution to be extrapolated to future studies in human.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bioengineering and Tissue Regeneration (LABRET), Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, Biomedical Research Institute of Málaga (IBIMA), University of Málaga, 29071 Málaga, Spain.

ABSTRACT
Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is an immune-mediated multifactorial disease, with high level of prevalence in humans and dogs. Our aim in this study was to investigate the therapeutic effects of allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) implanted around the lacrimal glands in 12 dogs (24 eyes) with KCS, which is refractory to current available treatments. Schirmer tear test (STT) and ocular surface integrity were assessed at 0 (before treatment), 3, 6, and 9 months after treatment. Average STT values and all clinical signs showed a statistically significant change (P < 0.001) during the follow-up with reduction in all ocular parameters scored: ocular discharge, conjunctival hyperaemia, and corneal changes, and there were no signs of regression or worsening. Implanted cells were well tolerated and were effective reducing clinical signs of KCS with a sustained effect during the study period. None of the animals showed systemic or local complications during the study. To our knowledge, this is the first time in literature that implantation of allogeneic Ad-MSCs around lacrimal glands has been found as an effective therapeutic alternative to treat dogs with KCS. These results could reinforce a good effective solution to be extrapolated to future studies in human.

No MeSH data available.


Related in: MedlinePlus

Cell morphology and proliferative curve of canine Ad-MSCs cultures. (a) In primary cultures, a large number of adherent cells with fibroblastic morphology were observed from the first day of culture, forming frequent CFUs. On secondary culture, canine Ad-MSCs appeared as spindle-shaped cells that were grown in a monolayer. Bars 200 μm. (b) Representative curve obtained with MTS cell proliferation assay at p2 showing from 24 hours an important proliferative capacity, initiating the logarithmic growth phase, and reaching its plateau phase around 14 days.
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fig1: Cell morphology and proliferative curve of canine Ad-MSCs cultures. (a) In primary cultures, a large number of adherent cells with fibroblastic morphology were observed from the first day of culture, forming frequent CFUs. On secondary culture, canine Ad-MSCs appeared as spindle-shaped cells that were grown in a monolayer. Bars 200 μm. (b) Representative curve obtained with MTS cell proliferation assay at p2 showing from 24 hours an important proliferative capacity, initiating the logarithmic growth phase, and reaching its plateau phase around 14 days.

Mentions: The subcutaneal fat pads from each dog were processed and the isolation of MSCs was successful in all donor samples. Canine Ad-MSCs were isolated using their ability to adhere to tissue culture plastic. In primary cultures, a large number of colony-forming units (CFUs) consisted of cells with fibroblastic morphology were observed 2 days after initial seeding and 80% of confluence was reached at day 6 (Figure 1(a)). On secondary cultures, canine Ad-MSCs appeared as spindle-shaped cells that were grown in a monolayer and maintained their proliferation capacity without indication of senescence.


Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model.

Villatoro AJ, Fernández V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA - Biomed Res Int (2015)

Cell morphology and proliferative curve of canine Ad-MSCs cultures. (a) In primary cultures, a large number of adherent cells with fibroblastic morphology were observed from the first day of culture, forming frequent CFUs. On secondary culture, canine Ad-MSCs appeared as spindle-shaped cells that were grown in a monolayer. Bars 200 μm. (b) Representative curve obtained with MTS cell proliferation assay at p2 showing from 24 hours an important proliferative capacity, initiating the logarithmic growth phase, and reaching its plateau phase around 14 days.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4352730&req=5

fig1: Cell morphology and proliferative curve of canine Ad-MSCs cultures. (a) In primary cultures, a large number of adherent cells with fibroblastic morphology were observed from the first day of culture, forming frequent CFUs. On secondary culture, canine Ad-MSCs appeared as spindle-shaped cells that were grown in a monolayer. Bars 200 μm. (b) Representative curve obtained with MTS cell proliferation assay at p2 showing from 24 hours an important proliferative capacity, initiating the logarithmic growth phase, and reaching its plateau phase around 14 days.
Mentions: The subcutaneal fat pads from each dog were processed and the isolation of MSCs was successful in all donor samples. Canine Ad-MSCs were isolated using their ability to adhere to tissue culture plastic. In primary cultures, a large number of colony-forming units (CFUs) consisted of cells with fibroblastic morphology were observed 2 days after initial seeding and 80% of confluence was reached at day 6 (Figure 1(a)). On secondary cultures, canine Ad-MSCs appeared as spindle-shaped cells that were grown in a monolayer and maintained their proliferation capacity without indication of senescence.

Bottom Line: Average STT values and all clinical signs showed a statistically significant change (P < 0.001) during the follow-up with reduction in all ocular parameters scored: ocular discharge, conjunctival hyperaemia, and corneal changes, and there were no signs of regression or worsening.Implanted cells were well tolerated and were effective reducing clinical signs of KCS with a sustained effect during the study period.These results could reinforce a good effective solution to be extrapolated to future studies in human.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bioengineering and Tissue Regeneration (LABRET), Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, Biomedical Research Institute of Málaga (IBIMA), University of Málaga, 29071 Málaga, Spain.

ABSTRACT
Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is an immune-mediated multifactorial disease, with high level of prevalence in humans and dogs. Our aim in this study was to investigate the therapeutic effects of allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) implanted around the lacrimal glands in 12 dogs (24 eyes) with KCS, which is refractory to current available treatments. Schirmer tear test (STT) and ocular surface integrity were assessed at 0 (before treatment), 3, 6, and 9 months after treatment. Average STT values and all clinical signs showed a statistically significant change (P < 0.001) during the follow-up with reduction in all ocular parameters scored: ocular discharge, conjunctival hyperaemia, and corneal changes, and there were no signs of regression or worsening. Implanted cells were well tolerated and were effective reducing clinical signs of KCS with a sustained effect during the study period. None of the animals showed systemic or local complications during the study. To our knowledge, this is the first time in literature that implantation of allogeneic Ad-MSCs around lacrimal glands has been found as an effective therapeutic alternative to treat dogs with KCS. These results could reinforce a good effective solution to be extrapolated to future studies in human.

No MeSH data available.


Related in: MedlinePlus