Bio-engineered Intestinal Replacement Therapy

M. Stelzner
VA Greater Los Angeles and UCLA Dept. of Surgery, Los Angeles, CA

Optimal nutrition is important for humans of any age. Yet a number of changes occur in the gastrointestinal tract throughout the lifetime of an individual including changes in the intestinal morphology and in the absorption of nutrient substances. In older people, these alterations can significantly decrease intestinal function and contribute to undernutrition or malnutrition. In diseased individuals, medical illnesses and surgical operations may further restrict or even eliminate the ability to absorb nutrients and vitamins in sufficient quantities. Patients affected by these problems are often critically ill and treatments options are limited.

Strategies to deal with severe, irreversible disturbances of nutrient absorption have traditionally included intestinal transplantation or continuous intravenous nutrition. However, neither of these treatment options is well tolerated as a long-term solution by any age group. A third approach is tissue engineering of intestine, and it has gained increasing attention over the past two decades. Tissue engineering aims at replacing dysfunctional or missing intestinal tissues with a neo-intestinal substitute that emulates the physiologic functions of the gut. A number of research groups have worked in their laboratories over years to bring us closer to a functional replacement intestine. They have developed techniques to harvest intestinal stem cell clusters from fetal or neonatal animals that can be grafted onto natural or synthetic carrier materials. Graft beds and growth conditions had to be carefully optimized.

Today, this methodology is relatively standardized and it enable us to generate neo-intestinal tissue that resembles native intestine in many morphologic features and functional characteristics. This neo-intestine has made it possible to improve or even cure clinical malabsorption syndromes in investigations using rodents. Recently the successful generation of neo-intestinal tissues in large mammals has been reported as well. These impressive successes are important steps toward the clinical application of intestinal tissue engineering technology in humans. The isolation of sufficient numbers of donor stem cells, the ability to isolate or propagate stem cells from adult donors, and methods to generate composite tissues with superior absorptive and neuromuscular functions are aspects that will require further efforts in the next few years.

Keywords: Intestine, Bioengineering, Malabsorption, Human