Stem Cell Therapy for Inflammatory Bowel Disease in the Works

Stem cells from umbilical cord blood have the ability to migrate to the intestine and integrate into the tissues. This integration allows umbilical stem cells to contribute to the cell population of the gastrointestinal tract. This biological property of umbilical cord stem cells might make them ideal treatments for inflammatory bowel disease (IBD).

One million Americans have IBDs such as Crohn’s disease or ulcerative colitis. Crohn’s disease can affect the small and large intestine, whereas the ulcerative colitis is usually restricted to the colon (large intestine). Also Crohn’s disease displays patchy lesions whereas ulcerative colitis consists of continuous stretches of inflammation. These disease are characterized by frequent diarrhea and abdominal pain. Patients who suffer from ulcerative colitis also tend to have bloody stools, and if left untreated, the blood loss can be extensive. Ulcerative colitis only affects the upper layer of the large intestine, whereas Crohn’s disease can affect multiple layers of the intestine.

There are no cures for IBDs, but there are drug treatments. In the case of ulcerative colitis, the drug prednisone is used to calm down fulminant outbreaks and then mesalamine (5-aminosalicylic acid) or sulfasalazine are used to maintain the disease in a calm or quiescent state. Mesalamine is present in an oral form marketed as Asacol or Pentasa. The difference between Asacol and Pentasa is in the outer chemical coating, since Pentasa packages its drug in coated microgranules, which enables a prolonged release of the active substance throughout the intestinal tract, from duodenum to the rectum. Therefore Pentasa is more useful for Crohn’s patients. Asacol is a delayed release enteric-coated tablets that releases the active ingredient only in the colon. Mesalamine is also available in an enema form (Rowasa)

If these drugs do not work, biologic treatments such as Infliximab (Remicade), adalimumab (Humira) and Golimumab (Simponi) are commonly used to treat patients with Ulcerative Colitis, but these drugs suppress the immune system and can raise the risk of severe illness. Corticosteroids are also used, but long-term use of these drugs also causes severe side effects.

Thus, if the drugs do not work, the treatment can be as bad as the disease itself. Certainly a treatment that regenerates the bowel is preferable, and a stem cell treatment seems to fit the bill.

In an article in the journal Hepatology, the senior author, Graca Almeida-Porada, a professor at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine, and her colleagues argue that a special stem cell population known as endothelial colony-forming cells, found in umbilical cord blood and bone marrow and circulating blood, can play a definite role in the treatment of IBDs.

Almeida-Porada said, “These cells are involved in the formation of blood vessels and may prove to be a tool for improving the vessel abnormalities found in IBD.”

In 1997, scientists discovered that these endothelial colony-forming stem cells contribute to the formation of blood vessels in embryos, and adults. This study initiated investigations of the capacity of endothelial colony-forming cells as potential therapeutic agents. Clinical studies have shown that endothelial colony-forming cells can improve reduced blood flow to limbs and can also treat heart disease.

Unfortunately, few studies have examined the ability of endothelial colony-forming cells to home to different organs and integrate into their circulatory systems. Thus, Almeida-Porada wanted to examine the ability of endothelial colony-forming cells to integrate into the intestine. Also, since abnormal blood vessels are a hallmark of IBDs, they might be a potential treatment for IBDs.

In this experiment, fetal sheep at 59-65 days gestation were injected with human endothelial colony-forming cells (EPCs). At 11 weeks gestation, the fetal sheep were examined to determine if the human cells had integrated into the fetal sheep tissue. Researchers found that the infused cells had migrated into the intestine and had made significant contributions to the cell population of the bowel.

According to Almeida-Porada: “The study shows that the cells can migrate to and survive in a healthy intestine and have the potential to support vascular health. Our next step will be to determine whether cells can survive in the ‘war’ environment of an inflamed intestine.”

Interestingly, Almeida-Porada’s team found that endothelial colony-forming cells also colonized the liver of the fetal sheep. Although smaller numbers of cells reached the liver as opposed to the intestine, new strategies might enhance the therapeutic potential for these cells with respect to the liver.