Mass. General team creates functional, stem-cell-derived small bowel segmentsOctober 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."
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:
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.
In diseases like cancer, diabetes, rheumatism and stroke, a disorder develops in the blood vessels that exacerbates the condition and obstructs treatment.
EPFL scientists have improved the efficacy of cancer immunotherapy by blocking two proteins that regulate the growth of tumor blood vessels.
Tumor cells use the bloodstream to spread in the body.
A team of researchers at Karlsruhe Institute of Technology shake at the foundations of a dogma of cell biology.
The PIEZO1 cation channel translates mechanical stimulus into a molecular response to control the diameter of blood vessels.
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.
After 20 years of searching, scientists discover the mystic gene controlling vessel and blood cell growth in the embryo.
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.
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:
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
HOW NOT To DIE BUT SURVIVE A PLAGUE: Best Guide To Survive Plagues And Live Longer
by DAVID A. OSEI (Author)
Surviving Plagues is the utmost desire of any living human being. Plagues do happen from time to time by virtue of either reckless lifestyle or poor environmental management breeding pest and rodents. Either way, plagues are deadly by its effects and so getting contracted by any type of plagues demands immediate action to remedy it. Even though advancement in living standard is reducing the spread of plagues, they are still present and active which when the environment is abused can quickly result into epidemic and outbreak. Plagues are everywhere, both in the advanced countries and the... 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
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
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
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
Heart Talk: Understanding Cardiovascular Diseases : An Authoritative Source on the Prevention, Diagnosis and Treatment of Heart and Blood Vessel Dis
by Mark V., Jr. Barrow (Author)
Explains how the heart and blood vessels work and discusses the prevention and diagnosis of cardiovasular diseases View Details
Telangiectasia: Procedures to Remove Dilated Blood Vessels Using the Blend Method
by Michael Bono (Author)
Removing dilated blood vessels using the blend method of technology. Michael Bono has taught blend technique in U.S., Canada, Japan, Germany, Holland and Peru View Details
Laboratory Medicine Diagnosis of Disease in Clinical Laboratory 2/E (Lange)
by Michael Laposata (Author)
A complete full-color guide to medical test selection and test result interpretation
A Doody's Core Title for 2017!
Laboratory Medicine is an essential text for medical students and residents studying clinical pathology, medical technology students, and for practitioners working in a clinical setting. By selecting the appropriate tests and interpreting the results correctly, physicians using this book should be able to optimize patient outcomes and reduce the cost of achieving a diagnosis.
This full-color guide features an easy-to-follow, consistent... View Details
Introduction to Vascular Ultrasonography: Expert Consult - Online and Print, 6e (Zwiebel, Introduction of Vascular Ultrasonography)
by John Pellerito MD (Author), Joseph F Polak MD MPH (Author)
Now in its 6th edition, Introduction to Vascular Ultrasonography, by Drs. John Pellerito and Joseph Polak, provides an easily accessible, concise overview of arterial and venous ultrasound. A new co-editor and new contributors have updated this classic with cutting-edge diagnostic procedures as well as new chapters on evaluating organ transplants, screening for vascular disease, correlative imaging, and more. High-quality images, videos, and online access make this an ideal introduction to this complex and rapidly evolving technique.Find information quickly with sections organized by... View Details