Corneal Ulcer with Descemetocele in a Cat Treated with Conjunctival Pedicle Graft and WJ-MSC Exosomes

A 5-year-old cat was presented with a history of severe ocular pain, blepharospasm, and excessive lacrimation of the right eye
Ophthalmic examination revealed a deep corneal ulcer involving more than 70% of the corneal thickness, with descemetocele formation at the central region

The lesion showed stromal melting, absence of epithelium

Fluorescein dye staining confirmed deep ulceration with imminent risk of corneal

The combined use of a conjunctival pedicle graft and WJ-MSC exosomes provided a synergistic healing effect in this case

History

Treatment

No history of trauma was initially noted, but bacterial infection secondary to chronic keratitis was suspected.

Due to the depth and extent of corneal damage, surgical intervention was indicated to preserve the globe

Surgical Management

A conjunctival pedicle graft was performed
A vascularized section of bulbar conjunctiva was mobilized and sutured onto the corneal defect ensuring full coverage of the ulcer and descemetocele region.
The graft provided structural support, nutrient supply, and blood-derived immune protection to the affected cornea.

2. WJ-MSC Exosome Therapy

Immediately post-surgery Wharton’s Jelly Mesenchymal Stem Cell (WJ-MSC)-derived exosomes were administered


WARTONJELLY MESENCHYMAL STEM CELL DERIVED EXOSOMES

WJ-MSC exosomes are tiny nanosized vesicles (30–150 nanometers in diameter) that are released by Wharton’s Jelly Mesenchymal Stem Cells — which come from the Wharton’s jelly of the umbilical cord (the soft connective tissue surrounding the umbilical vessels)a


Source:
WJ-MSCs are derived from the Wharton’s jelly of the umbilical cord, a rich and ethically accessible source of stem cells.

Characteristics:

  • Multipotent — can differentiate into fibroblasts, endothelial cells, adipocytes, osteocytes, and others.
  • Exhibit anti-inflammatory, immunomodulatory, and tissue-repairing properties.
  • Low immunogenicity — can be used allogenically (from donor to recipient) without rejection



Stimulate fibroblast proliferation and collagen type III synthesis (early healing matrix).


Promote angiogenesis (formation of new blood vessels).


Suppress inflammation and oxidative stress.


Inhibit myofibroblast overactivation, which is responsible for scar tissue and contracture formation.


Clinical Benefits in Wound healing :


Accelerated Wound Healing:

Exosomes boost regeneration of skin, muscle, and connective tissue, leading to faster closure and recovery.


Reduced Inflammation and Infection Risk:

Their immunomodulatory effects minimize local inflammation and secondary infection.


Scar-Free Healing:

By collagen remodeling and reducing fibrotic signaling

WJ-MSC exosomes promote regeneration rather than repair, resulting in smoother, more natural skin texture.


Improved Skin Quality and Pigmentation:

Encourages normal melanocyte function and organized dermal structure, leading to uniform color and elasticity.


Enhanced Integration of Surgical Repair:

In reconstructive procedures, exosomes help grafted or sutured tissues integrate seamlessly with surrounding skin.


Neuroprotective and Angiogenic Effects:

Support recovery of minor nerve and vascular injury often associated with deep facial cuts.

1. Immunomodulatory Effects Against Tumor Cells


WJ-MSCs have a remarkable ability to modulate the immune response, which can indirectly suppress tumor growth:


They enhance anti-tumor immunity by stimulating natural killer (NK) cells, cytotoxic T lymphocytes, and macrophages to attack abnormal cells.


They secrete immunoregulatory cytokines such as:


Interferon-γ (IFN-γ) and Tumor Necrosis Factor-α (TNF-α) – increase cytotoxic immune activity.


Interleukin-10 (IL-10) and TGF-β – regulate excessive inflammation but maintain immune surveillance.


WJ-MSCs can downregulate tumor-supportive inflammatory cytokines (IL-6, IL-8, and IL-1β), which are often involved in tumor proliferation and angiogenesis.


2. Induction of Tumor Cell Apoptosis


Several studies have shown that WJ-MSCs can induce apoptosis (programmed cell death) in certain tumor cells through multiple mechanisms:


Release of pro-apoptotic factors such as TRAIL (TNF-related apoptosis-inducing ligand) and caspase activators.


Cell-to-cell contact via gap junctions or exosomes can trigger apoptosis in neoplastic cells.


Modulation of mitochondrial pathways leading to apoptotic cell death.


This effect varies depending on tumor type more evident in epithelial or carcinoma-type cells, which include trichoblastiomas .


3. Inhibition of Tumor Cell Proliferation


WJ-MSCs can slow tumor progression through paracrine signaling that alters the local environment:


Secretion of growth-inhibitory molecules which block proliferative signaling pathways


Inhibition of angiogenesis in neoplastic tissue ( depriving the tumor of its blood supply )


exosomes containing microRNAs that downregulate oncogenic genes in tumor cells.


4. Remodeling of the Tumor Microenvironment (TME)


WJ-MSCs can transform a tumor-supportive microenvironment into a hostile environment for tumor survival:


Reduce oxidative stress and inflammatory mediators that promote mutagenic activity.


Recruit anti-tumor immune cells and limit infiltration of tumor-associated macrophages which typically protect tumors.


5. Anti-Angiogenic Effects


Tumor growth depends on new vessel formation (angiogenesis). WJ-MSCs can counter this by:


Secreting angiogenesis inhibitors


Downregulating VEGF and PDGF signaling in nearby endothelial cells.


Reducing the density of microvessels in the tumor bed, thus starving the tumor of oxygen and nutrients.


6. Exosome-Mediated Anti-Cancer Activity


WJ-MSC-derived exosomes play a central role in cell-to-cell communication and can deliver anti-oncogenic microRNAs and proteins directly to tumor cells:


These exosomes carry miRNAs that target oncogenes


They can block cell cycle progression, inhibit epithelial-mesenchymal transition (EMT), and reduce metastasis potential.


Their nano-size allows them to reach deep tumor tissues efficiently without immunologic rejection.


7. Selective Cytotoxicity and Safety


Unlike chemotherapeutic drugs, WJ-MSCs do not damage healthy cells. They exhibit selective inhibition of rapidly dividing or mutated cells while promoting repair of normal tissue.


This dual function anti-tumor + regenerative makes them ideal therapeutic option

--Topical application: a sterile exosome suspension was applied directly onto the cornea and graft bed.

-Subconjunctival injection: small volumes were infiltrated adjacent to the graft margins.

The exosome therapy was continued topically once daily for the first week and then every 48 hours for two additional weeks.

deep corneal ulcer with descemetocele formation

Conjunctival pedicle graft covering the ulcerated corneal and descemetocele

Conjunctival pedicle graft covering the ulcerated corneal and descemetocele

Conjunctival pedicle graft covering the ulcerated corneal and descemetocele

neovascular sprouts begun to extend from the graft

The graft gradually became less edematous and the corneal surface appeared smoother

The conjunctival graft started to blend with native corneal tissue

Neovascularization toward the center of the cornea

Neovascularization toward the center of the cornea

the graft became more lucent and shrunk in size

Corneal surface became more clear with minimal opacity of the graft that will gradually reduce with time

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