Thursday, 28 February 2013

Scientists identify stem cells that may one day treat inflammatory bowel disease

In a study published today, scientists from the Wake Forest Baptist Medical Centre (WFBMC) have discovered two adult stem cell populations in bone marrow tissue that have the capacity to both migrate to the intestine and differentiate into intestinal cells. The study has implications in the treatment of inflammatory bowel disease (IBD).

IBD is a group of inflammatory, autoimmune conditions, affecting more than 1 million people in the U.S. alone. The two most common types of IBD are Crohn's disease and ulcerative colitis. Unfortunately, there is no real treatment for the condition, although there are various drugs that reduce the inflammation and the auto-immune response. This is why many researchers are currently working on methods involving stem cells to someday offer an alternative therapeutic approach.

In this study the researchers, led by Graca Almeida-Porada, used special cell markers and identified two types of bone marrow adult stem cells that could be used for treating IBD. According to Porada, one of the stem cell types is involved in blood vessel formation whereas the other can regenerate intestinal cells and modulate the inflammation. He hopes that a combination of these stem cells may one day be used to create an injectable therapy for IBD.

The identified stem cells express high levels of a receptor called ephrin type B (EphB2), which has an important role in tissue regeneration and wound closure. The cells were first cultured and then injected into fetal sheep, at 55 to 62 days gestation.


Computer generated image of the EphB2 protein

At 75 days post-gestation, it was found that the vast majority of the cells had migrated in an intestinal gland known as the crypt of Lieberk├╝hn. From there, they replenished the native intestine stem cell population. This indicates that these stem cells can be used to regenerate tissue in IBD patients by creating new cells from within the intestine. Porada says that previously published literature indicates that cells derived from bone marrow tissue can aid in the recovery of the gastrointestinal tract in IBD patients.

"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." said Porada


Micrograph showing inflammation of the large bowel in an IBD case
Micrograph showing inflammation of the large bowel in an IBD case

It should be noted that in 2012, Porada and his team had published another study, where they had identified a cord blood stem cell population which again was involved in blood vessel formation and had the capacity to transfer into the intestine.

Porada now plans to take the findings of these studies a step further and examine whether or not these stem cells can actually survive in an inflamed intestine.


As mentioned before the two main forms of IBD are Crohn's disease and ulcerative colitis. There are other forms of IBD, however they account for far fewer cases. Some of them are the following:
  • Collagenous colitis
  • Lymphocytic colitis
  • Ischaemic colitis 
  • Diversion colitis
  • Beh├žet's disease
  • Indeterminate colitis


Video about Crohn's disease and ulcerative colitis



References
- Wood, J., Colletti, E., Mead, L., Ingram, D., Porada, C., Zanjani, E., Yoder, M., & Almeida-Porada, G. (2012). Distinct contribution of human cord blood-derived endothelial colony forming cells to liver and gut in a fetal sheep model Hepatology, 56 (3), 1086-1096 DOI: 10.1002/hep.25753
- Colletti E, El Shabrawy D, Soland M, Yamagami T, Mokhtari S, Osborne C, Schlauch K, Zanjani ED, Porada CD, & Almeida-Porada G (2013). EphB2 isolates a human marrow stromal cell subpopulation with enhanced ability to contribute to the resident intestinal cellular pool. FASEB journal : official publication of the Federation of American Societies for Experimental Biology PMID: 23413357

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