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Stem Cells From the Heart Could Treat Crohn’s Disease

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In a mouse model of Crohn’s disease (CD), scientists from the Ann & Robert H. Lurie Children’s Hospital of Chicago injected neonatal cardiac-derived mesenchymal stem cells (nMSCs) directly into inflammatory lesions. The first-of-its-kind study, published in Advanced Therapeutics, may offer new treatment avenues for the debilitating illness. 

Developing cell therapies for CD

CD is a type of inflammatory bowel disease (IBD), a group of conditions that affect 1 in 100 Americans. Named after Dr. Burrill B. Crohn who described the disease in 1932, CD is characterized by chronic inflammation and lesions within the gastrointestinal (GI) tract. While the entire portion of the GI tract can be inflamed, the final section of the small intestine – known as the ileum – is often most severely affected by lesions or “patches” of CD. Patients with the condition can experience severe diarrhea, abdominal pain, weight loss, malnutrition and other debilitating symptoms that adversely affect quality of life.

Treatment approaches for CD include immune modulators, immune suppressive regimens, corticosteroids and aminosalicylates. Unfortunately, patients can experience severe side effects to such regimens and may develop treatment insensitivity. Scientists – including researchers at the Ann & Robert H. Lurie Children’s Hospital of Chicago – are pursuing novel avenues such as cell therapies.

The team had previously demonstrated that nMSCs improve cardiac function recovery and immune cell modulation In animal models of myocardial infarction (a heart attack). Utilizing their resource of neonatal cardiac tissue obtained through patient biopsies, they turned their attention to a preclinical model of CD-like ileitis. Could cardiac-derived nMSCs produce a positive effect on the lesions observed in CD?

Ileitis is the term given to inflammation occurring specifically in the ileum. In this study, the researchers used the “SAMP” model, which is considered a gold-standard approach to studying the pathogenesis of chronic intestinal inflammation and testing the effects of interventions.

What are mesenchymal stem cells?

Mesenchymal stem cells (MSCs) are a type of stem cell that are found throughout the human body. Bone marrow is the most commonly used source, but MSCs can also be obtained from umbilical tissue and adipose tissue among others.

“Neonatal cardiac-derived mesenchymal stem cells have been used in a clinical trial to repair an injured heart, but this is the first time these potent cells have been studied in an inflammatory intestinal disease model,” says Dr. Arun Sharma, director of pediatric urological regenerative medicine and surgical research at Ann & Robert H. Lurie Children’s Hospital. Sharma is also a research associate professor of urology and biomedical engineering at Northwestern University Feinberg School of Medicine and the McCormick School of Engineering, Northwestern University.

Cell therapy reduces inflammation and promotes cell regeneration in CD

Sharma and colleagues injected nMSCs directly into inflammatory lesions within the small intestine of the mice. Lesion progression was compared in pre-treatment SAMP mice at 10 weeks of age and then at 15 weeks of age (5 weeks after injection). Placebo-controlled groups of SAMP mice were included in the study, receiving either no injection or an injection of saline instead of nMSCs. “At pre-injection, ileal lesion sizes were comparable across all the conditions and between the groups,” the researchers note. Histological examination of the colon tissue showed that the nMSCs attenuated inflammation and promoted epithelial cell regeneration in the ileum in treated mice. “Our results are encouraging and definitely provide a new platform to potentially treat aspects of chronic inflammatory bowel diseases,” says Sharma.

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“The mechanism for increased nMSCs retention in the inflammatory milieu at post-five-week treatment remains unknown as does the safety profile that also needs to be further investigated,” the researchers note, suggesting that with this data, nMSCs could be a feasible alternative to current cell therapies adopted in CD treatment. Sharma adds that an additional hurdle to overcome is the route of delivery for the treatment. In the study, the nMSCs were injected directly into the lesions, requiring surgery. The team are exploring how the treatment could be delivered through injection into a vein, but additional work in pre-clinical models will be required before progressing to clinical trials.

“Ultimately our goal is to utilize this cell type as treatment, but also as a preventive measure, before signs and symptoms of CD develop. We also might be able to apply this approach to other inflammatory diseases. The potential is enormous, and we are excited to move forward,” Sharma concludes.

Reference: Gunasekaran M, Bury MI, Sharma TT, et al. Multipotent human neonatal cardiac-derived mesenchymal stem cells modulate ileitis in vivo. Adv Therap. 2023;n/a(n/a):2200261. doi:10.1002/adtp.202200261

This article is a rework of a press release issued by Ann & Robert H. Lurie Children’s Hospital of Chicago. Material has been edited for length and content.