Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model

Villatoro, Antonio J; Fernández, Viviana; Claros, Silvia; Rico-Llanos, Gustavo A.; Becerra, José; Andrades, José A.

doi:10.1155/2015/527926

Cited by 88 publications

(93 citation statements)

References 40 publications

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“…Therefore, this report agrees with the findings of other authors that corroborate demonstrating beneficial results of the use of stem cells in veterinary in general (Bakker et al, 2013) and especially in the treatment of ophthalmopathies in several species, both for CU in several species (Sel et al, 2012;Ma et al, 2006) as for other diseases such as keratoconjunctivitis sicca (Villatoro et al, 2015).…”

Section: Discussionsupporting

confidence: 93%

Treatment for Canine Corneal Ulcer using Adipose Tissuederived Mesenchymal Stem Cell Therapy - Case Report

Arantes-Tsuzuki¹,

Mazzonetto²,

Turco³

2019

Preprint

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Corneal ulcer (CU) is an ophthalmopathy characterized by depression of the corneal surface with at least one stromal loss. CU is common in canine and feline species and is usually caused, among others, by trauma, infections, toxic contamination and endocrine disorders. They usually result from an increased inflammatory response and are associated with some clinical signs such as blepharospasm, photophobia, epiphora, pain and loss of corneal transparency. Despite advances in conventional and pharmacological therapy, in many cases indolent and recurrent ulcer treatments still lead to loss of visual acuity of the animal. This paper aims to report the effect of topical application of canine adipose tissue-derived mesenchymal stem cell (cATMSCs) as treatment of recurrent CU in a Poodle dog breed that showed clear difficulty in the healing process associated with diabetes. The animal was submitted to two applications of cATMSCs and showed improvement in the blepharospasm, conjunctival hyperemia, mucopurulent ocular secretion, photophobia, corneal opacity, chemosis, pigmentation, neovascularization, and pain parameters. Besides, Fluorescein test, Schirmer test and ocular fundus exam also showed improvement in their values concomitantly with lesion resolution. Due this, we showed that cATMSC therapy contribute to the regeneration of corneal tissue in CU and may contribute to the treatment to others ophthalmopathies.

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Section: Discussionsupporting

confidence: 93%

Treatment for Canine Corneal Ulcer using Adipose Tissuederived Mesenchymal Stem Cell Therapy - Case Report

Arantes-Tsuzuki¹,

Mazzonetto²,

Turco³

2019

Preprint

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“…For example, it was reported recently that intrathecal injection of MSC in dogs with idiopathic meningoencephalitis resulted in clinical improvement [41]. Local injection of MSC has also been used in the management of keratoconjunctivitis sicca in dogs, an immune-mediated disorder that results in loss of tear production [42]. Human embryonic stem cell-derived MSC were also reported recently to suppress inflammation associated with furunculosis in dogs, an inflammatory disease of the peri-rectal tissues of canines [43].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

ChowLyndah

JohnsonValerie

CoyJonathan

et al. 2017

Stem Cells and Development

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Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC) and adipose-derived MSC (Ad-MSC) been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, and differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-b signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase, TGF-b and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-b pathways for T cell suppression, rather than on NO or IDO-mediated pathways.

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“…In practical terms, this means that these spheroids should be administered as soon as possible after manufacture to DES patients. Application of cell spheroids as opposed to single cell suspensions, which has been evaluated by others (Lee et al, ; Park et al, ; Villatoro et al, ; Weng et al, ), is preferable since transplant efficiency is increased (i.e., there is less chance of mislocation of transplanted graft). We were able to scale down manufacture from 48‐ to 96‐well plates to produce spheroids measuring approximately 2 mm in diameter, and these could conceivably be injected directly into the periorbital space.…”

Section: Discussionmentioning

confidence: 99%

Development of lacrimal gland spheroids for lacrimal gland tissue regeneration

Massie

Spaniol

Barbian

et al. 2018

J Tissue Eng Regen Med

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Severe dry eye syndrome resulting from lacrimal gland (LG) dysfunction can cause blindness, yet treatments remain palliative. In vitro reconstruction of LG tissue could provide a curative treatment. We aimed to combine epithelial cells with endothelial cells and mesenchymal stem cells (MSCs) to form a 3D functional unit. Epithelial cells and MSCs were isolated from porcine LG; endothelial cells were isolated from human foreskin. MSCs were characterised (flow cytometry and differentiation potential assays). All 3 cell types were combined on Matrigel and spheroid formation observed. Spheroids were characterised [immunohistochemistry (IHC) and transmission electron microscopy] and function assessed (β-hexosaminidase assay). Spheroids were transferred to decellularised jejunum (SIS-Muc) in dynamic cultures for 1 week before further characterisation. MSCs did not express CD31 but expressed CD44 and CD105 and differentiated towards osteogenic and adipogenic lineages. Spheroids formed on Matrigel within 18 hr, contracting to ~10% of the well area (p < .005). IHC revealed presence of all 3 cells within spheroids. Transmission electron microscopy revealed cell-cell contacts and polarisation at the apical surface. In static cultures, function was increased in spheroids cf. monolayer controls (p < .05) but over 72 hr, spheroid function (p < .05), viability (p < .05), and proliferation decreased, whilst apoptosis increased. On SIS-Muc under dynamic culture, however, spheroids continued to proliferate to repopulate SIS-Muc. IHC revealed LG epithelial cells coexpressing pan-cytokeratin and lysozyme, as well as endothelial cells and MSCs and cells remained capable of responding to carbachol (p < .05). These spheroids could form the basis of a regenerative medicine treatment approach for dry eye syndrome. In vivo studies are required to evaluate this further.

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Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model

Cited by 88 publications

References 40 publications

Treatment for Canine Corneal Ulcer using Adipose Tissuederived Mesenchymal Stem Cell Therapy - Case Report

Treatment for Canine Corneal Ulcer using Adipose Tissuederived Mesenchymal Stem Cell Therapy - Case Report

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

Development of lacrimal gland spheroids for lacrimal gland tissue regeneration

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