Tales from the Crypt: Penn Study on Gut Cell Regeneration Reconciles Long-Standing Research Controversy

PHILADELPHIA - The lining of the intestine regenerates itself every few days as compared to say red blood cells that turn over every four months. The cells that help to absorb food and liquid that humans consume are constantly being produced. The various cell types that do this come from stem cells that reside deep in the inner recesses of the accordion-like folds of the intestines, called villi and crypts.

But exactly where the most important stem cell type is located -- and how to identify it -- has been something of a mystery. In fact, two types of intestinal stem cells have been proposed to exist but the relationship between them has been unclear. One type of stem cell divides slowly and resides at the sides of intestinal crypts. The other divides much more quickly and resides at the bottom of the crypts.

Some researchers have been proponents of one type of stem cell or the other as the "true" intestinal stem cell. Recent work published this week in Science from the lab of Jonathan Epstein, MD, chairman of the Department of Cell and Developmental Biology from the Perelman School of Medicine at the University of Pennsylvania, may reconcile this controversy. The findings suggest that these two types of stem cells are related. In fact, each can produce the other, which surprised the researchers.

"We actually began our studies by looking at stem cells in the heart and other organs," Epstein said.  "In other tissues in the body, slowly dividing cells can sometimes give rise to more rapidly dividing stem cells that are called to action when tissue regeneration is required.  Our finding that this can happen in reverse in the intestine was not expected."

The discovery that rapidly cycling gut stem cells can regenerate the quiescent stem cells -- slowly dividing and probably long-lived -- suggests that the developmental pathways in human organs that regenerate quickly like in the gut, skin, blood, and bone, may be more flexible than previously appreciated.

"This better appreciation and understanding may help us learn how to promote the regeneration of tissue-specific adult stem cells that could subsequently help with tissue regeneration," says Epstein.  "It may also help us to understand the cell types that give rise to cancer in the colon and stomach."

Co-authors are, all from Penn, Norifumi Takeda, Rajan Jain, Matthew R. LeBoeuf, Qiaohong Wang, and Min Min Lu.  The work was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health and by the Penn Institute for Regenerative Medicine.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.