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Engineered Colons: Medicine’s Next Big Thing?

Did you know that every two weeks your intestine completely regenerates its lining itself? It’s because of this incredible regenerative capacity that doctors believe intestines are the perfect organ to regrow. Now, a new medical breakthrough could help children born with gastrointestinal defects.

“I was so scared I didn’t know what was going to happen,” Stacy Lara told Ivanhoe.

At 18 weeks pregnant, Stacy Lara was told something was terribly wrong with her son.

“He had quite a bit of bowel outside of his abdomen,” Stacy said.

Nathan had a birth defect that caused his intestine to grow outside of his body.

“He really only has a few inches of intestines, whereas a baby this age would normally have maybe six to eight feet of intestine,” Russ Merritt, MD, PhD, Medical Director of Intestinal Rehabilitation Program at Children's Hospital Los Angeles, told Ivanhoe.

For Nathan that means a lifetime of being fed through a tube or a transplant, but Dr. Tracy Grikscheithopes a discovery in her lab can change the prognosis for Nathan and other children like him.  

“We’ve been able to show that we can make every part of the gastrointestinal tract, we can make esophagus, stomach, small intestine, and colon,” Tracy Grikscheit, MD, Principal Investigator, The Saban Research Institute, and Surgeon at Children's Hospital Los Angeles, was quoted as saying.

After children have surgery, doctors take tissue from the waste left over and then re-grow the cells in the lab, within months an organ can be made. Dr. Grikscheit says it would eliminate risk of organ rejection and a lifetime of medication.

“If we were able to make engineered intestine from your own cells it would be part of you, grow with you. It would repair itself,” Dr. Tracy Grikscheit said.

It’s a medical breakthrough that could have patients healing themselves. 

 

BACKGROUND: Sometimes children are born without portions of their intestines.  One cause of this is necrotizing enterocolitis (NEC).  NEC is a gastrointestinal disease that affects mostly premature infants.  It involves infections and inflammation that causes destruction of the bowel (intestine) or part of the bowel.  NEC is the most common and serious gastrointestinal disorder among hospitalized preemies.  However, it affects only one in 2,000 to 4,000 premature births.  It usually occurs the first couple weeks of life.  Around ten percent of babies weighing less than 3 lbs., 5 oz. (1,500 grams) have NEC.  (Source: www.kidshealth.org)

 

CAUSES:  The cause of NEC is unknown, but a theory is that the intestinal tissues of premature infants are weakened by too little oxygen or blood flow.  When feedings start, the added stress of food moving through the intestine allows bacteria normally found in the intestine to invade and damage the wall of the intestinal tissues.  The damage can affect a short segment of the intestine or can progress quickly to involve a larger portion.  Infants are unable to continue feedings.  They can also develop imbalances in the minerals in the blood.  In severe cases of NEC, a hole can develop in the intestine, which allows bacteria to leak into the abdomen.  Some experts believe that the makeup of infant formula, the immaturity of the mucous membranes in the intestines, and the rate of delivery of the formula can cause NEC.  Babies who are fed breast milk can also develop NEC, but the risk is lower.  Another theory is that babies born through difficult deliveries with lowered oxygen levels can develop NEC.  When babies don’t have enough oxygen, their bodies will send the available oxygen and blood to vital organs instead of the gastrointestinal tract, resulting in NEC.  Babies with an increased number of red blood cells also seem to be at an increased risk for developing NEC.  Too many red blood cells can thicken the blood and hinder the transport of oxygen to the intestines.  (Source: www.kidshealth.org)

 

NEW TECHNOLOGY:  Current treatment involves surgery to remove the affected portions of the intestine, or if the condition is severe, an intestinal transplant may be necessary.  Both options come with significant problems.  If the intestine is too short, it could be unable to perform its functions.  Also, any transplant comes with sever risks.  Patients who get intestinal transplants are on anti-rejection medications for the rest of their lives.  The medications affect the immune system, causing infants to be more prone to other illnesses.  However, researchers at Children’s Hospital Los Angeles have successfully grown a tissue-engineered human colon.  The concept is still in its early stages, but their goal is to offer alternative treatment for children who are born without portions of their intestine, or who require surgery to have portions of their intestine removed.  Tracy Grikscheit, MD, Principal Investigator at The Saban Research Institute and Surgeon at Children's Hospital Los Angeles, used the patient’s own stem cells from the intestine to regrow portions of the colon.  Now, they used the procedure to regrow small amounts of the small intestine, a process that takes four weeks.  Dr. Grikscheit received a $3.4 million grant to fund the steps required before the first trial can take place for engineered intestines.  One of the steps will be to define characteristics of patients who would have the most success form the procedures. (Source: http://www.dailynews.com/marathon/ci_22341148/tissue-engineered-colon-will-help-treat-children)

 

Tracy Grikscheit, MD, Principal Investigator at The Saban Research Institute and Surgeon at Children's Hospital Los Angeles, talks about a new breakthrough that is building organs for children. 

How many kids are affected by this?

Dr. Grikscheit: The incidences are relatively low, but it’s actually rising because it happens more in babies who are born prematurely. We are getting much better at saving those kids. So, more and more babies go on to develop a disease called necrotizing enterocolitis. Also, intestinal problems in early childhood and even in adulthood can lead to intestinal failure. However, it is primarily a problem for newborns.

What is life like for these babies?

Dr. Grikscheit:  I think it’s something that’s hard to watch and that’s why my whole lab is involved in this area and why Children’s Hospital Los Angeles has an intestinal failure program. The basic problem is that because the child can’t get enough nutrition from absorbing food alone they have to receive IV nutrition.  Over time, the IVs won’t last, so they have to have a central line that travels all the way to the heart to deliver nutrition. Over time those lines can break down and become infected. The child may require multiple surgeries to keep the access site open so that the nutrition can pass through the IV. So,  you can imagine that a lot of effort goes into just ensuring that the child is getting proper nutrition.  it is a lot to put on a kid who should be playing, not spending time in the hospital and not having all of these higher medical needs.

So how does tissue engineering come into this?

Dr. Grikscheit: Well, this won’t be the solution for every child. It’s not a solution that’s available today. Children with intestinal failure have to have some of their intestines removed.With tissue engineering, we are trying to compensate for that loss of intestine.. Just like when you get sunburned and you know that your skin is going to heal over time, there are stem cells in the intestines that can also regenerate. In fact your intestine every two weeks completely re-lines itself.  That’s remarkable.  We need to be able to harness that incredible regenerative capacity to grow new intestines for the children from their own cells.

What have you been able to accomplish so far?

Dr. Grikscheit:  So far, we’ve been able to show that we can make every part of the gastrointestinal tract, but in small amounts and it is not ready for people yet. However, we can make esophagus, stomach, small intestine, and colon. We can make those tissues that actually have all of the functions that you would require. They have the right cells, nerves, and blood vessels.  We have tested some of them out as replacements in preclinical models, and they have worked.

How do you get these stem cells to grow into that specific organ?

Dr. Grikscheit: The intestine has a lot of different functions and so you need to have a complex set of cells. These cells can be gathered from the intestine of human donors. When children at our hospital have surgery, and there is some tissue left over that needed to be removed, we can actually take the cells from that intestine, including the nerve cells, the lining of the intestine, and the muscle. We can break them down into little clumps. Then, when we grow those clumps of cells, we’re able to regenerate all the parts of the intestine.

So, you use a patient’s own cells to create their replacement intestine?

Dr. Grikscheit: That is the absolute goal of our lab and the objective that all of us are working toward.

So, you are eliminating the need for an organ transplant and the need for a lifetime of immunosuppressive drugs, correct?

Dr. Grikscheit: Exactly.  To us, it’s a huge advantage. When we do a transplant the average hospitalization after transplant can sometimes be up to 180 days for a small bowel transplant. That is half a year. That’s a long time for a family and for a baby. You can imagine if you require that much time for recovery that you must be very ill. In addition, after that you need to take drugs to suppress the immune system so that you don’t reject the transplant. So if we were able to make engineered intestine from your own cells it would be part of you and grow with you. It would self-repair and you wouldn’t need any medication to make sure that you didn’t reject it.

Could these babies actually never know they had a problem?

Dr. Grikscheit: That would be our absolute hope. We want to fix the problem almost before it happens. So, when we are in the operating room and we know that a child has this problem, we’d like -- at that very moment -- to start making more intestine for the child so that before he or she runs into problems with their liver or infections, we hopefully, would have already regenerated the organ that they will need. That’s far in the future, though. That’s not happening this year.

How long does it take to grow intestine, colon, and esophagus?

Dr. Grikscheit: It’s surprisingly quick. In this lab, we aren’t growing a sufficient quantity for a baby. We definitely can grow baby intestine and show that it is human tissue-engineered intestine that’s growing. We also generally grow small amounts so that we can work on the function and improve the growth process. That takes about four weeks. It will probably take a little bit longer to generate enough for babies.

So, when is this going into clinical trials?

Dr. Grikscheit:  We’ve gotten a lot of funding through the California Institute for Regenerative Medicine and we are very grateful for their support. The latest grant, which we’re all working on, is to translate this process to human therapy. This is the future for our lab and for these children.

You can learn more about Dr. Grikscheit’s research at: http://www.chla.org/site/c.ipinktoajsg/b.7970553/k.a420/grikscheit_lab__tissue_engineering__intestinal_regeneration__stem_cells.htm#.uci_qljd_gg

 

 

FOR MORE INFORMATION, PLEASE CONTACT:

 

Ellin Kavanagh

Associate Director of Research Communication

The Saban Research Institute of

Children’s Hospital Los Angeles

(323) 361-8505

ekavanagh@chla.usc.edu


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