Researchers Discover A New Liver Cell that Shows Promise for Cellular Therapy for Liver Regeneration
New research from the Icahn School of Medicine at Mount Sinai, published in the journal Cell Stem Cell today, suggests that it may one day become possible to regenerate a liver using cell therapy in patients with liver disease.
Liver transplantation is the mainstay of treatment for patients with end-stage liver disease, the 12th leading cause of death in the United States, but new research from the Icahn School of Medicine at Mount Sinai, published in the journal Cell Stem Cell today, suggests that it may one day become possible to regenerate a liver using cell therapy in patients with liver disease. Investigators discovered that a human embryonic stem cell can be differentiated into a previously unknown liver progenitor cell, an early offspring of a stem cell, and produce mature and functional liver cells.
"The discovery of the novel progenitor represents a fundamental advance in this field and potentially to the liver regeneration field using cell therapy," said the study's senior author, Valerie Gouon-Evans, PharmD, PhD, Assistant Professor, in the Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, at the Icahn School of Medicine at Mount Sinai. "Until now, liver transplantation has been the most successful treatment for people with liver failure, but we have a drastic shortage of organs. This discovery may help circumvent that problem."
In conjunction with the laboratory of Matthew J. Evans, PhD, from the Department of Microbiology at Icahn School of Medicine at Mount Sinai, investigators demonstrated the functionality of the liver cells generated from the progenitors, as the liver cells can be infected by the hepatitis C virus, a property restricted to liver cells exclusively.
A critical discovery in this research was finding that the novel progenitor has a receptor protein on its cell surface called KDR, or vascular endothelial growth factor receptor 2, which until now, was thought to be restricted to endothelial cells that form vessels, the progenitors for endothelial cells and the progenitors blood cells. The research team showed that activation of KDR on these novel liver progenitors differentiates them into mature liver cells. Additionally, work in a mouse model revealed similar cells, indicating that the progenitors are conserved from mouse to human, and therefore, they must be "important cells with promising potential for cell therapy in treating liver disease," explained Dr. Gouon-Evans.
Next, the research team will examine specifically whether these liver cells obtained from human embryonic stem cells in a dish help repair injured livers in preclinical animal models of liver disease.
Funding for this study was provided by The Black Family Stem Cell Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Robin Chemers Neustein Postdoctoral Fellowship, the American Cancer Society, and Pew Charitable Funds.
About The Black Family Stem Cell Institute
The Black Family Stem Cell Institute is Mount Sinai’s foundation for both basic and disease-oriented research on embryonic and adult stem cells. The therapeutic use of stem cells is a promising area of medicine for the decades ahead and researchers are examining why stem cells function in certain types of niches, microenvironments, and pockets of activity. Investigators are working to break the code in stem cell communication by determining how stem cells signal one another and other cells. The new knowledge that will result from this research holds the promise of diagnostic and therapeutic breakthroughs.
Studies show that it is possible to reprogram adult skin cells into cells that are very similar to embryonic stem cells. Once stem cells can be grown and differentiated in a controlled way to replace degenerated cells and repair tissues, medical science may then be able to diagnose and cure many intractable diseases at their earliest stages, such as type 1 diabetes, Parkinson’s disease, various cardiovascular diseases, liver disease, and cancer.
For more information, visit http://icahn.mssm.edu/research/institutes/black-family-stem-cell-institute/about-us
The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2011, U.S. News & World Report ranked The Mount Sinai Hospital 16th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Of the top 20 hospitals in the United States, Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology, Mount Sinai St. Lukes and Mount Sinai West are ranked 23rd nationally for Nephrology and 25th for Diabetes/Endocrinology, and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally.