Nav: Home

Mass. General team creates functional, stem-cell-derived small bowel segments

October 10, 2017

Using human induced pluripotent stem cells (iPSCs), a Massachusetts General Hospital research team has bioengineered functional small intestine segments that, when implanted into rats, were capable of deliver nutrients into the bloodstream. The investigators describe their accomplishment in the online journal Nature Communications.

"In this study we have been able to bridge the gap between differentiation of single cells - driving stem cells to become a specific cell type - and the generation of tissue that shows a higher level of function - in this instance vascular perfusion and nutrient absorption," says Harald Ott, MD of the MGH Department of Surgery and the Center for Regenerative Medicine, senior author of the report. "While previous studies have reported successful differentiation of organoids - millimeter-small units of tissue - from iPSCs, we describe a technology that enables these smaller units of tissue to form larger-scale grafts that someday could be used as implanted replacement organs.

Several serious gastrointestinal diseases, including Crohn's disease, may lead to removal of all or part of the small intestine, leading to a condition called short bowel syndrome. While it sometimes can be treated with special diets, many patients need to rely on intravenous nutrition. While small bowel transplantation is a feasible treatment option, its availability is very limited because of the organ shortage. For example, while 127 transplants were performed in the U.S. in 2015, as of October 4, 2017, 273 patients remained on the waiting list.

As with previous studies from Ott's team, this one utilizes a procedure he developed in 2008 for stripping the living cells from a donor organ with a detergent solution and then repopulating the remaining extracellular matrix scaffold with organ-appropriate types of cells. His team has decellularized animal kidneys, lungs and hearts; generated functional rat kidneys and lungs, and last year regenerated functional heart muscle in decellularized human hearts. In this study, the MGH team used that same approach to decellularize 4 cm segments of rat small intestine and confirmed the applicability of the procedure to larger animals in segments of pig intestine.

While the decellularized small intestine would provide the structural scaffold for both the complex tissue of the interior lining and the vascular channels, repopulating the scaffold requires the delivery, engraftment and maturation of two types of cells - epithelial cells for the intestinal lining and endothelial cells for the blood vessels - in the right locations. Generation of epithelial tissue began with human iPSCs that were differentiated into intestinal precursor cells and then seeded into the interior of the decellularized segments, which then were cultured. Two weeks later, after formation of the epithelial layer, human endothelial cells were seeded into the vascular channels; and the segments placed in a perfusion bioreactor system for further maturation.

Several days later, in vitro testing of the segments confirmed blood passage through the repopulated vasculature and showed that the reconstituted intestinal tissue could transfer glucose and fatty acids from the interior of segments into the blood vessels. The repopulated epithelial cells lining the segments had the same polarized structure - with the proteins lining cellular membranes on the interior of the segments differing from those at the base of the cells - seen in naturally occurring intestinal epithelium.

A few of the segments were sutured to the carotid arteries and jugular veins of immunodeficient rats. The vasculature of the segments was immediately perfused with blood, and four weeks later injections of either glucose or fatty acids into the segments resulted in increased levels in the animals' bloodstreams, confirming absorption of the nutrients. In addition, specific types of cells normally found in the intestinal lining that had not appeared while the segment were cultured did after implantation into the living animals, implying continued maturation of the tissue.

"Our in vivo experiments showed that human iPSCs differentiated towards an intestinal fate can be assembled into an intestinal graft with a high level of organization and connected to a recipient's vasculature to enable nutrient absorption after transplantation," says Ott, who is an associate professor of Surgery at Harvard Medical School. "The next steps will be to further mature these grafts and to scale the construct to a human size, so that someday we may be able to provide a more accessible alternative to small bowel transplantation for patients with short bowel syndrome - ideally growing 'on-demand' patient-specific grafts that would not require immunosuppressive drugs."
-end-
Kentaro Kitano, MD, of the MGH Department of Surgery and the University of Tokyo, is lead author of the Nature Communications paper. Additional co-authors are Dana Schwartz, MD, Haiyang Zhou, MD, Sarah Gilpin, PhD, Xi Ren, PhD, Douglas Mathisen, MD, and Allan Goldstein, MD, MGH Surgery; Gregory Wojtkiewicz, MS, MGH Center for Systems Biology; and Cesar Sommer, PhD, Amalia Capilla, PhD, and Gustavo Mostoslavsky, MD, PhD, Boston University School of Medicine. Support for the study includes National Institutes of Health Director's New Innovator Award DP2 OD008749-01, the Charles and Sara Fabrikant MGH Research Scholar Award, and a grant from the Mendez National Institute of Transplantation Foundation.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $850 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2017 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."

Massachusetts General Hospital

Related Blood Vessels Articles:

Study: Use of prefabricated blood vessels may revolutionize root canals
Researchers at OHSU in Portland, Oregon, have developed a process by which they can engineer new blood vessels in teeth, creating better long-term outcomes for root canal patients and clinicians.
New findings on formation and malformation of blood vessels
In diseases like cancer, diabetes, rheumatism and stroke, a disorder develops in the blood vessels that exacerbates the condition and obstructs treatment.
Targeting blood vessels to improve cancer immunotherapy
EPFL scientists have improved the efficacy of cancer immunotherapy by blocking two proteins that regulate the growth of tumor blood vessels.
Reprogrammed blood vessels promote cancer spread
Tumor cells use the bloodstream to spread in the body.
Neurons modulate the growth of blood vessels
A team of researchers at Karlsruhe Institute of Technology shake at the foundations of a dogma of cell biology.
Sensor for blood flow discovered in blood vessels
The PIEZO1 cation channel translates mechanical stimulus into a molecular response to control the diameter of blood vessels.
Blood vessels control brain growth
Blood vessels play a vital role in stem cell reproduction, enabling the brain to grow and develop in the womb, reveals new UCL research in mice.
No blood vessels without cloche
After 20 years of searching, scientists discover the mystic gene controlling vessel and blood cell growth in the embryo.
New way of growing blood vessels could boost regenerative medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Regenerating blood vessels gets $2.7 million grant
Biomedical engineers in the Cockrell School of Engineering at The University of Texas at Austin have received $2.7 million in funding to advance a treatment that regenerates blood vessels.

Related Blood Vessels Reading:

Heart, Lungs and Blood Vessels - Their Descriptions, Functions and Diseases: Useful Heart, Lung and Blood Vessel Information – Condensed For Easy Learning (0001)

In the "Heart, Lungs and Blood Vessels - Their Descriptions, Functions and Diseases" eBook, we keep similar terms “Grouped Together” for easy comparison. This helps you learn faster and easier, and prevents confusion. Also, with this proven learning method, you will save time, and learning will be more thorough.

As an example, when you read the Section on “Types of Blood Vessels”, and look for the definition of the term “Vein", you will also learn the difference between a “Vein, Artery, and a Capillary” because all these similar terms are “Grouped Together”... View Details


Blood Vessels like a Teenager: Insider-cures against atherosclerosis
by Christian Meyer-Esch (Author)

Many people in the western world suffer from massive circulatory disorders due to obstructed blood vessels. In this book, you will learn how exactly these deposits are formed, what kind of deposits there are, and how to avoid them, but also to easily resolve them. Any claims are proven by scientific studies. After reading this book, you will be an expert on blood vessels. They will have knowledge about what doctors have not usually been taught in medicine. Again, clean blood vessels of a teenager! To treat and prevent heart attack, stroke and circulatory disorders. With my new immediate... View Details


Inflammatory Diseases of Blood Vessels
by Gary S. Hoffman (Editor), Cornelia M. Weyand (Editor), Carol A. Langford (Editor), Jorg J. Goronzy (Editor)

In recent years, considerable progress has been made in understanding the vasculitic diseases, largely due to the introduction of effective treatments for diseases that were once uniformly fatal, the conduct of structured clinical studies, and advances in immunology and molecular biology. Despite these achievements, the vasculitic diseases continue to be associated with morbidity and mortality from chronic organ damage, relapses, and the side effects of treatment. Investigations into the mechanisms of vascular inflammation may lead to a better comprehension of the pathogenesis of vasculitic... View Details


Human Body (Discovery Kids)
by Parragon Books (Author)

Discover the secrets of the human body. Using stunning illustrations and cutaway diagrams, Human Body takes you on a fascinating visual journey of this most complex of machines, showcasing the brilliance of the human anatomy along the way. Satisfy the curiosity of the most inquisitive minds and discover the secrets of the body with this concise reference book for all the family. Explore the human body in minute detail, from microscopic cells to the large intestine. Features key information on the vital organs and their functions. Learn all about the skeleton and examine joints and muscles in... View Details


LIPITOR (Atorvastatin): Treats High Cholesterol and Triglyceride Levels; and Reduces the Risk of Angina, Stroke, Heart Attack, or Certain Heart and Blood Vessel Problems
by James Lee Anderson (Author)

“Although, your health condition may impact your everyday life, do not let it define who you are.” LIPITOR (atorvastatin) is used together with diet, weight loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. LIPITOR (atorvastatin) is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density... View Details


Human Body!
by DK (Author)

The ultimate kids' guide to the human body, with computer-generated 3-D imagery that shows them the body as they've never seen it before, from the award-winning publisher of Knowledge Encyclopedia.

This visual encyclopedia includes astonishing, all-new 3-D artworks, offering a fascinating view of every part of the body from the skull to the heart and lungs to the joints and muscles, taking kids from head to toe. Supporting STEM education initiatives, all the body systems and structures are made easy to understand. Both the anatomy—how the body looks—and the... View Details


Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life
by Kate Rheaume-Bleue (Author)

The secret to avoiding calcium-related osteoporosis and atherosclerosis

While millions of people take calcium and Vitamin D supplements thinking they're helping their bones, the truth is, without the addition of Vitamin K2, such a health regimen could prove dangerous. Without Vitamin K2, the body cannot direct calcium to the bones where it's needed; instead, the calcium resides in soft tissue (like the arteries)--leading to a combination of osteoporosis and atherosclerosis, or the dreaded "calcium paradox." This is the first book to reveal how universal a Vitamin K2 deficiency is, and the... View Details


Little Book for Heart and Blood Vessel Health: What is my risk for heart attack or another vascular event? How do I achieve goal?
by Philip H. Frost M.D. (Author)

The premise of this Little Book is that the learned individual will be motivated to seek assistance in reducing his/her risk of suffering a vascular event. This book provides the reader with language to understand lipid measurements, background to consider risk assessment, lipid goals, and tools currently available to achieve risk factor reduction. Patient stories illustrate not only the myriad of problems that are encountered, but methods employed to achieve success - ideal lipids. View Details


Inflammatory Diseases of Blood Vessels
by Gary S. Hoffman (Author), Cornelia M. Weyand (Author)

This comprehensive reference emphasizes the dynamic events that occur in the maintenance and repair of blood vessels in health and abnormalities that may result from dysregulation of inflammatory and immune responses in disease. The editors have assembled authors and topics that bring new concepts about cell and molecular biology to the clinician to provide a better understanding of pathogenesis, the diagnostic process, and treatment. Recent insights into pathogenesis have dramatically influenced development of new therapies that target disease pathways.

Inflammatory Diseases of Blood... View Details


Pathology of the cerebral blood vessels
by William E Stehbens (Author)

View Details

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Manipulation
We think we're the ones who control what we see, read, think and remember. But is that true? Who decides? And who should decide? This hour, TED speakers reveal just how easily we can be manipulated. Guests include design ethicist Tristan Harris, MSNBC host Ali Velshi, psychologist Elizabeth Loftus, and neuroscientist Steve Ramirez.
Now Playing: Science for the People

#443 Batteries
This week on Science for the People we take a deep dive into modern batteries: how they work now and how they might work in the future. We speak with Gerbrand Ceder from UC Berkeley, about the most commonly used batteries today, how they work, and how they could work better. And we talk with Kathryn Toghill, electrochemist from Lancaster University, about redox flow batteries and how they could help make our power grids more sustainable.