Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lab-developed intestinal organoids form mature human tissue in mice

20.10.2014

Study produces unprecedented model to study intestinal diseases

Researchers have successfully transplanted "organoids" of functioning human intestinal tissue grown from pluripotent stem cells in a lab dish into mice – creating an unprecedented model for studying diseases of the intestine.


Michael Helmrath, M.D., M.S., surgical director of the Intestinal Rehabilitation Program at Cincinnati Children's Hospital Medical Center, talks about researchers successfully growing human intestinal tissue in mice. The study describes an unprecedented model for studying diseases of the intestine. Reporting their results Oct. 19 in Nature Medicine, the scientists said through additional translational research, the findings could eventually lead to bioengineering personalized human intestinal tissue to treat gastrointestinal diseases.

Credit: Cincinnati Children's Hospital Medical Center

Reporting their results Oct. 19 online in Nature Medicine, scientists from Cincinnati Children's Hospital Medical Center said that, through additional translational research the findings could eventually lead to bioengineering personalized human intestinal tissue to treat gastrointestinal diseases.

"These studies support the concept that patient-specific cells can be used to grow intestine," said Michael Helmrath, MD, MS, lead investigator and surgical director of the Intestinal Rehabilitation Program at Cincinnati Children's. "This provides a new way to study the many diseases and conditions that can cause intestinal failure, from genetic disorders appearing at birth to conditions that strike later in life, such as cancer and Crohn's disease. These studies also advance the longer-term goal of growing tissues that can replace damaged human intestine."

The scientists used induced pluripotent stem cells (iPSCs) – which can become any tissue type in the body – to generate the intestinal organoids. The team converted adult cells drawn from skin and blood samples into "blank" iPSCs, then placed the stem cells into a specific molecular cocktail so they would form intestinal organoids.

The human organoids were then engrafted into the capsule of the kidney of a mouse, providing a necessary blood supply that allowed the organoid cells to grow into fully mature human intestinal tissue. The researchers noted that this step represents a major sign of progress for a line of regenerative medicine that scientists worldwide have been working for several years to develop.

Mice used in the study were genetically engineered so their immune systems would accept the introduction of human tissues. The grafting procedure required delicate surgery at a microscopic level, according to researchers. But once attached to a mouse's kidney, the study found that the cells grow and multiply on their own. Each mouse in the study produced significant amounts of fully functional, fully human intestine.

"The mucosal lining contains all the differentiated cells and continuously renews itself by proliferation of intestinal stem cells. In addition, the mucosa develops both absorptive and digestive ability that was not evident in the culture dish," Helmrath said. "Importantly, the muscle layers of the intestine also develop."

What This Means for Patients

The new findings eventually could be good news for people born with genetic defects affecting their digestive systems or people who have lost intestinal function from cancer, as well as Crohn's disease and other related inflammatory bowel diseases (IBD).

One of the advantages of using tissue generated from iPSCs is that the treatment process would involve the patient's own tissue, thus eliminating the risk and expense of life-long medications to prevent transplant rejection.

However, the researchers cautioned that it will take years of further research to translate lab-grown tissue replacement into medical practice. In the meantime, the discovery could have other, more immediate benefits by accelerating drug development and the concept of personalized medicine.

The current process for developing new medications depends on a long and imperfect process of animal testing. Promising compounds from the lab are tested in animals bred to mimic human diseases and conditions. Many compounds that prove effective and safe in mice turn out to be unsuccessful in human clinical trials. Others have mixed results, where some groups of patients clearly benefit from the new drug, but others suffer harmful side effects.

Lab-grown organoids have the potential to replace much of the animal testing stage by allowing early drug research to occur directly upon human tissue. Going straight to human tissue testing could shave years off the drug development process, researchers said.

The current study in Nature represents the latest step in years of stem cell and organoid research at Cincinnati Children's, much of which has been led by James Wells, PhD, and Noah Shroyer, PhD. Wells is a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children's and director of the Pluripotent Stem Cell Center. Shroyer is a scientist in the divisions of Gastroenterology, Hepatology & Nutrition and Developmental Biology.

Wells and colleagues first reported success at growing intestinal organoids in the lab in December 2010. Since then, the team has reported similar success at growing organoids of stomach tissue.

Also collaborating were researchers at the Department of Internal Medicine, University of Michigan (Ann Arbor, Mich.)

###

Funding support for the study came in part from: the National Institutes of Health (DK092456; U18NS080815; R01DK098350; DK092306; CA142826; R01DK083325; P30 DK078392; UL1RR026314; K01DK091415 P30DK034933; DK094775).

About Cincinnati Children's:

Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2014 Best Children's Hospitals. It is also ranked in the top 10 for all 10 pediatric specialties. Cincinnati Children's, a non-profit organization, is one of the top three recipients of pediatric research grants from the National Institutes of Health, and a research and teaching affiliate of the University of Cincinnati College of Medicine. The medical center is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at http://www.cincinnatichildrens.org. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.

Nick Miller | Eurek Alert!

Further reports about: Biology Medicine diseases human tissue intestinal pluripotent stem cells stem cells

More articles from Life Sciences:

nachricht In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin

nachricht How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

Im Focus: Nanorobots propel through the eye

Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.

Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

In focus: Peptides, the “little brothers and sisters” of proteins

12.11.2018 | Life Sciences

Materials scientist creates fabric alternative to batteries for wearable devices

12.11.2018 | Materials Sciences

A two-atom quantum duet

12.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>