Potential anti-inflammatory effects of mesenchymal stem cells or their extracellular vesicles on gene expression and T cell responses in plasma and intestine of dogs with inflammatory bowel disease (IBD)

Sponsor: Private Foundation

IACUC Protocol # G2016-134

Status:  Enrollment currently on hold

Description:

Dogs develop inflammatory bowel disease (IBD) spontaneously, which results in persistent or recurring signs such as weight loss, vomiting, and/or diarrhea, and is characterized by inflammatory cell infiltration in the intestine.

In both humans and dogs, IBD is considered to be an idiopathic, chronic, relapsing immune-mediated inflammatory disorder of the GI tract that involves the interplay between genes, diet, and the microbes in the intestine. The treatment for IBD in both dogs and humans is similar, and relies on diet, immune suppression.

The goals of this experiment are: 1) to evaluate the gene expression of the white blood cells in the intestine and the blood of dogs with inflammatory bowel disease compared to normal dogs, and 2) to evaluate the in vitro response to activation of the T cells in the blood and intestine of dogs with IBD and normal dogs, and 3) to determine in vitro if extracellular vesicles (EV) derived from canine mesenchymal stem cells (MSC) or the MSC themselves are able to reduce the inflammation seen in dogs with IBD.

MSC are cells derived from the tissue around the umbilical cord, which are known to have anti-inflammatory and regenerative properties. EV are nanoparticles released from the MSC, which contain many signaling molecules that are also potentially capable of anti-inflammatory properties.

Inclusion Criteria:

IBD group:

Dogs over 1 year of age and weighing > 5 kg undergoing upper gastrointestinal endoscopy for evaluation of a history of chronic gastrointestinal signs of at least 3 weeks duration (vomiting, diarrhea, and/or weight loss) will be considered. These dogs will have no identifiable cause for their clinical signs on routine diagnostic evaluation (complete blood count, serum chemistry, urinalysis, baseline cortisol). Dogs will need to have had a veterinarian-recommended diet trial for at least 1 week with incomplete resolution of signs, as well as be incompletely responsive to an antibiotic trial with metronidazole or tylosin. Eligible dogs will have had a negative fecal floatation and Giardia ELISA or negative zinc sulfate floatation, or be non-responsive to a treatment course with fenbendazole (50 mg/kg daily for 3 days).

Control dogs for blood and GI tissue acquisition will include otherwise healthy dogs undergoing endoscopy for foreign body retrieval and weighing > 5 kg. Dogs will have no evidence of systemic disease (change in weight, thirst, urination, activity level), and no history of gastrointestinal signs unrelated to recent foreign body ingestion.

Exclusion Criteria:

Dogs with cancer detected on physical examination or diagnostics performed will be excluded. Dogs cannot be on topical or oral short acting steroid therapy (prednisone or prednisolone), other oral immunosuppressants (i.e., azathioprine, cyclosporine), or oral non-steroidal anti-inflammatory (i.e., Rimadyl, Deramaxx) medication for at least 1 week prior to biopsy. Antibiotic therapy will not exclude a patient from enrollment.

Client Benefits:

Fees associated with histopathology (microscopic evaluation of the intestinal tissue) performed during the study will be covered during your participation in the study. Costs incurred by additional anesthesia time over that needed for diagnostic biopsy collection or foreign body removal will be covered by the study.

In the event any complications arise during endoscopy, their management will be covered by you.

Contact Information:

For questions regarding the clinical trial please email the clinical trials technician, Diane Welsh at: clinicaltrials@tufts.edu