Mount Sinai Researchers Report Insights into Blood Stem Cells from Engineered Stem Cells
Building upon previous work, researchers at the Icahn School of Medicine at Mount Sinai identified cells in the embryos of mice that are precursors to blood stem cells or hematopoietic stem/progenitor cells (HSPCs). In previous studies, they reprogrammed mouse skin cells in the lab to become HSPCs. Now, they have identified a precursor cell in the placenta and embryo of mice that can be matured in the lab to make HSPCs. Their study, titled, "Hematopoietic Reprograming In Vitro Informs in Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells," establishes that the reprogramming process can work back and forth in blood cell development. Their results, published online today in the journal Developmental Cell, could eventually lead to a process of developing patient-specific HSPCs and more differentiated blood products for cell-replacement therapy.
The need for transplantable stem cells is great for patients suffering from blood diseases such as leukemia, lymphomas, multiple myeloma and immune deficiency. Researchers are looking at ways to produce large numbers of HSPCs in the laboratory and developing methods for growing patient-specific HSPCs. The reprogramming process developed by researchers at Icahn School of Medicine at Mount Sinai appears to mimic normal blood cell creation or developmental hematopoiesis -- going from precursor cells to cells that eventually become HSPCs. This technology could potentially provide a different source of stem cells and alleviate this problem.
The team analyzed mouse placentas and embryos for the presence of cells with the same phenotype as the precursor cells, and confirmed that they could be matured to HSPCs in the lab.
“To cure disease in the long-term, we need to be able to transplant something that can keep producing new blood cells and won’t be rejected by the patient’s body,” said the senior author of the study, Kateri Moore, DVM, Associate Professor of Developmental and Regenerative Biology at the Icahn School of Medicine at Mount Sinai. “We are excited by the results of our study. The precursor cells can be matured in the lab to transplantable HSPCs. Our reprogramming process can inform developmental hematopoiesis and vice versa.”
Other members of the research team included Ihor R. Lemischka, PhD, Professor of Developmental and Regenerative Biology, Pharmacology and Systems Therapeutics and member of The Black Family Stem Cell Institute and first author Carlos-Filipe Pereira, PhD, former Postdoctoral Fellow of Developmental and Regenerative Biology at the Icahn School of Medicine at Mount Sinai, currently an Assistant Professor at the University of Coimbra, Portugal, Cell Institute.
"Direct reprogramming studies can improve applications for regenerative medicine," said Dr. Lemischka. "Many investigators have attempted to do what we have been able to do growing HSPCs in vitro, but we have been able to build upon this process that could move the field forward. The next step is to test these findings in humans."
"Our team has made great attempts to unlock this puzzle, working together for over 20 years in the fields of hematopoiesis and stem cell biology," said Dr. Moore, senior author of the study. "Our ultimate goal is to grow blood forming cells in the lab and improve efficiencies to generate patient-specific blood cells. This study brings us a step closer to reaching this goal.”
The research was funded by grants from the National Institutes of Health National Heart, Lung, and Blood Institute. Mount Sinai Innovation Partners is managing the intellectual property for this cell replacement technology on behalf of the Mount Sinai researchers.
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 us here.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.