Imagine - Growing Hope










It’s a child’s dream to be invincible -- to be able to regrow injured body parts after a make-believe battle. But what if this superhuman power was real? Scientists in the Developmental Biology and Regenerative Medicine Research program at The Saban Research Institute of Children’s Hospital Los Angeles are working to make it possible.

As the rates of diabetes, chronic kidney disease and short bowel syndrome increase in the U.S., more pediatric patients with damaged organs must turn to life-altering procedures such as transplants and dialysis. These invasive treatments offer a temporary solution, but patients often face complications due to the need for lifelong medications and the gradual deterioration of their “replacement parts.”

“We rely heavily on transplants and pharmaceuticals to treat serious diseases, despite significant limitations in these approaches. The ideal treatment would be the regeneration and repair of damaged areas by our own body,” says Roger De Filippo, MD, physician and principal investigator in Pediatric Urology at The Saban Research Institute and associate professor of Urology at the Keck School of Medicine of the University of Southern California (USC). “A cut on our arm gradually heals as the skin is replaced by new cells. Who’s to say that this can’t be done in our more vital organs?”

With hopes of making this treatment option a reality, De Filippo and Laura Perin, PhD, director of research in Pediatric Urology at the Institute and assistant professor of Urology at the Keck School of Medicine of the University of Southern California, are studying cell-based strategies for treating organ damage. They are currently testing a specific type of stem cell, derived from amniotic fluid, in the repair of tissues damaged by kidney, pancreas and lung diseases. Amniotic fluid stem cells, housed in an embryo’s surrounding liquid, release specialized molecules to spark tissue repair and regeneration. And they are easy to collect.

Amniotic fluid is safely obtained during amniocentesis, a common diagnostic procedure used during pregnancy. Stem cells are isolated from the fluid and can be used in laboratory models with chronic kidney, pancreas and lung diseases. In recent tests, De Filippo and Perin have demonstrated that amniotic fluid stem cells are able to stimulate tissue repair in living, breathing organisms.

“Our early findings show that amniotic fluid stem cells are able to induce regenerative mechanisms of repair in the diseased organ. They also increased the life span of the treated animals,” says Perin. “The success of these specific stem cells in living models allows us to establish a precedent for regenerative medicine in the treatment of chronically ill patients.” “By using human cells to regenerate the tissue in damaged areas,” concludes De Filippo, “we can hopefully restore structure and function in the safest way.”

This goal is shared by Tracy Grikscheit, MD, who is using tissue-engineering techniques to develop treatments for short bowel syndrome (SBS). As its name suggests, SBS occurs when the majority of the small intestine is missing or fails to function correctly, leading to profound dehydration and malnutrition.

“Ridges and folds along the length of the small intestine provide the expansive surface area for nutrient absorption into the body,” says Grikscheit, a pediatric surgeon at Children’s Hospital, principal investigator at The Saban Research Institute and assistant professor of Surgery at the Keck School of Medicine of USC. “This crucial length can be lost after intestinal failure due to infection, trauma, surgery, cancer or prematurity.”

Current treatments for SBS include total parenteral nutrition (TPN), a type of intravenous feeding, and transplants to replace the missing tissue. Unfortunately, prolonged use of TPN is associated with liver failure and sepsis, and organ transplants have only a 67 percent survival rate after five years.

“Long term, these options are still not good enough. When we think about treating children, we need a solution that will last a lifetime,” says Grikscheit. “To improve patient outcomes, my lab is working to engineer human intestinal tissue in hopes that SBS patients will one day be able to grow their own missing intestine. This would bypass the need for supplementary nutrition, invasive surgeries and lifelong medications.”

Grikscheit’s latest work expands upon previous proof-of-concept studies to test the viability of tissue-engineered small intestines for humans. In a study recently published in the Journal of Pediatric Surgery, Grikscheit collected the small intestine’s functional units from donated surgical tissue. The units were placed on supporting scaffolds and allowed to incubate and grow. After one month, the regrown intestine was examined with astonishing results.

“The tissue-engineered intestine is definitely growing from human cells,” says Grikscheit. “The sample contained a specific protein marker found only on cells of human origin.” Each of the four differentiated types of epithelial cells found in the human small intestine were also found in the engineered small intestine.

“This accomplishment brings us one step closer to offering the most personalized therapy to our patients,” notes Grikscheit. “Our next steps will be to understand which patients have cells that grow well so that we know who will respond best to this therapy. And we always want to make this treatment safer, more efficient and more reliable -- key factors we intend to work out before an approved clinical trial.”

From chronic kidney disease to various forms of intestinal failure, tissue engineering may one day give patients the ability to regrow their damaged organs and successfully fight back against disease. The technology may take several years to become available for patient use, but the recent work by De Filippo, Perin and Grikscheit gives hope that regenerative superpowers are on the horizon.