Stem Cell Therapy for Inflammatory Bowel Disease


Graca Almeida-Porada is professor of regenerative medicine at Wake Forest University in the Wake Forest Baptist’s Institute for Regenerative Medicine. Dr. Almeida-Porta and her colleagues have identified a special population of stem cells in the bone marrow that can migrate to the intestine and regenerate the intestine. Thus this stem population might provide a treatment for inflammatory bowel diseases or IBDs.

Approximately one million Americans have IBDs, and the main IBDs are ulcerative colitis, which is restricted to the large intestine, and Crohn’s disease, which involves the small and large intestine. These IBDs result from the immune system recognizing some component of the gastrointestinal system as foreign. and the immune system then attacks the gastrointestinal system as though it was a foreign invader. The result is chronic inflammation in the gastrointestinal tract, pain, bloody stools, redness and swelling of the bowel, in some severe cases, rupture of the bowel and death.

There are no cures for IDBs, but several drugs that suppress the immune response against the bowel, such as mesalamine (marketed as Asacol), sulfasalazine (Azulfidine), balsalazide (Colazal) and olsalazine (Dipentum) can reduce inflammation and assuage the symptoms of IBDs. However, there is no treatment to replace the damaged and dead cells in the bowel that result from the inflammation. Even though the bowel does regenerate to some degree, these extra bouts of cell proliferation can increase the patient’s risk of colon cancer. Is there a stem cell treatment to regenerate the bowel?

Research from Almeida-Porada’s laboratory has identified stem cells from umbilical cord blood that can make blood vessels that can also migrate to the intestine and liver (Wood JA, et al., Hepatology. 2012 Sep;56(3):1086-96). Now work in her lab has extended this original observations.

“We’ve identified two populations of human cells that migrate to the intestine – one involved in blood vessel formation and the other that can replenish intestinal cells and modulate inflammation,” said Almeida-Porada. She continued: “Our hope is that a mixture of these cells could be used as an injectable therapy to treat IBD.”

These cells would theoretically contribute cells to the intestine and facilitate and induce tissue healing and recovery. The lining of the intestine has one of the highest cellular turnover rates in the body. Intestinal cell types are being renewed weekly from this pool of intestinal cells that are in an area of the intestine known as the crypt.

In this current study, Almeida-Porada’s team used specific cell surface proteins (cell markers) to identify a stem cell population in human bone marrow that possesses the highest potential to migrate to the intestine and thrive in the intestine. These intestine-bound cells expressed high levels of a protein called ephrin type B, which is typically found on the surfaces of cells involved in tissue repair and wound closure.

Ephrin Protein Structure
Ephrin Protein Structure

When these ephrin type B-enriched bone marrow cells were injected into fetal sheep, the bone marrow-derived cells were able to migrate to the intestine and contribute to the growth and development of the sheep intestine.  Interestingly, these cells took up their positions in the intestinal crypts.

Almeida-Porada comment on her work:  “Previous studies in animals have shown that the transplantation of bone-marrow-derived cells can contribute to the regeneration of the gastrointestinal tract in IBD.  However, only small numbers of cells were successfully transplanted using this method.  Our goal with the current study was to identify populations of cells that naturally migrate to the intestine and have the intrinsic ability to restore tissue health.”

While these two studies show that the cells can migrate to and survive in a healthy intestine, the next step will be to determine whether they can survive in an inflamed intestine, like the type found in IBD patients.  In could be that preconditioning of the cells is required, as in the case of stem cell treatments for the heart after a heart attack.

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).