LAB DEVELOPED ORGANOIDS FORM HUMAN TISSUE IN MICE
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
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.
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