In this episode of the Disease Du Jour podcast, Liara Gonzalez, DVM, PhD, DACVS-LA, discussed her research on equine intestinal injury and recovery. Gonzalez’s lab was the first to develop a large animal pig model to study intestinal stem cells. It was also the first to identify these cells in horses and to grow intestinal stem cells into enteroids derived from pigs and horses. Her research is advancing our understanding of intestinal disease through expanded knowledge and use of equine intestinal stem cells in modulating mucosal barrier repair following ischemic damage.
This episode of Disease Du Jour is brought to you by Equithrive.
Intestinal Ischemia Research
Much of Gonzalez’s research has focused on intestinal ischemia, which occurs when blood supply to the intestine is obstructed, often due to strangulating lesions. The resulting lack of oxygenated blood causes rapid and sometimes irreversible intestinal damage. The sooner horses with strangulating lesions can undergo surgery, the better the outcome. However, practitioners often struggle to diagnose these lesions early. Additionally, intraoperative decision-making and postoperative complications are major hurdles to survival and recovery.
“Intraoperatively, we struggle to always know whether the intestine will have the capacity to repair itself or not,” Gonzalez explained. “Postoperatively, we struggle with knowing whether the intestine will regain its ability to function normally, and sometimes those horses have a lot of complications like reflux and laminitis.”
Her research has aimed to harness the power of stem cells to predict intestinal viability and surgical outcomes, as well as to promote intestinal healing.
“If we can harness those cells, perhaps we can help the intestine heal faster. If the intestine can heal faster, it would prevent some of these serious complications that we deal with postoperatively,” she explained. “Maybe [stem cells] could help us to predict colic earlier. Maybe they could help us say whether the intestine needs to be resected or removed or not. So, I think there’s a lot of potential in understanding stem cells in the context of the intestine specifically.”
Stem Cell Identification
During her PhD work, Gonzalez and a team of graduate students optimized the process of growing horse stem cells in a dish. They created enteroids, or “mini guts,” by isolating intestinal crypts, placing them in a matrix that supports their structure, and supplying them with growth factors and mediators. These mini guts resemble the inner lining of the horse’s intestine and grow large enough to be seen without a microscope.
“The potential is that we can now test therapies specifically to say, in a very controlled manner, will this treatment [with stem cells] enhance the regenerative capacity? And that’s taking out all the other factors that can sometimes muddy our results when we’re looking at a whole horse,” Gonzalez said. “If we can say in a dish, we can identify the right dosage, know the frequency that we need to supply the cells, and then translate it to treating a horse, I think we have the potential to more effectively determine whether a treatment actually is going to have a positive effect or not.”
Impact on Colic Management
Gonzalez’s research has shed light on the intestine’s remarkable capacity to repair itself. She said that earlier in her career, she would have been more likely to remove damaged intestine during colic surgery. “Doing this research has really given me the confidence to know that in certain cases, not all, there is a capacity [to repair], and we just need to be able to support the animal long enough,” she said.
Gonzalez’s lab is currently working on research that might change how we manage colic in the future. One area of research involves maintaining the intestine on a device outside the body and inducing ischemic injury, allowing them to better understand how injury occurs and to test different therapeutics. They are also working on developing biomarkers that could help veterinarians assess the severity and underlying cause of colic early in the disease process and quickly determine whether the horse needs to be referred.
Listen to the episode to learn more about Gonzalez’s research.
About Dr. Liara Gonzalez
Liara Gonzalez, DVM, PhD, DACVS-LA, is a veterinarian, specialty trained in large animal surgery, with a clinical and research focus on intestinal disease. Gonzalez’s research has aimed to develop and utilize large animal models to translate lab bench findings into clinically relevant therapeutic interventions that benefit both human and veterinary patients.
She is particularly interested in identifying improved means to determine tissue viability following severe intestinal injury, studying the role of intestinal stem cells in modulating mucosal barrier repair following ischemic damage, and developing normothermic machine perfusion to improve intestinal transplant patient outcomes. The research done in her lab has created the groundwork to utilize porcine tissue for the study of intestinal stem cells, including porcine crypt isolation and 3D culture. Ongoing work utilizes the tools developed to ask basic science questions, test novel biologics, and advance therapeutic options for patients suffering from severe intestinal disease. Gonzalez is driven to apply her knowledge and expertise in advanced laboratory techniques to solve clinically significant problems and further elucidate therapeutic targets to ultimately improve patient survival. Outside of work, Gonzalez enjoys her family, rowing, horseback riding, and travel.
You can find Gonzalez’s publications here.
Related Reading
- Risk Factors for Equine Strangulating Lipoma Colic
- Preventing Incisional Infections Following Colic Surgery
- Preoperative Fasting Increases Post-Anesthetic Colic Risk in Horses
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