Mount Sinai Researchers Succeed in Programming Blood Forming Stem Cells
Study is first step towards generating patient-specific blood products for cell-replacement therapy
By transferring four genes into mouse fibroblast cells, researchers at the Icahn School of Medicine at Mount Sinai have produced cells that resemble hematopoietic stem cells, which produce millions of new blood cells in the human body every day. These findings provide a platform for future development of patient-specific stem/progenitor cells, and more differentiated blood products, for cell-replacement therapy.
The study, titled, "Induction of a Hemogenic Program in Mouse Fibroblasts," was published online today in CELL STEM CELL. Mount Sinai researchers screened a panel of 18 genetic factors for inducing blood-forming activity and identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6 as sufficient to generate blood vessel precursor cells with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1 and Prominin1 within a global endothelial transcription program.
"The cells that we grew in a petri dish are identical in gene expression to those found in the mouse embryo and could eventually generate colonies of mature blood cells," said the first author of the study, Carlos Filipe Pereira, PhD, Postdoctoral Fellow of Developmental and Regenerative Biology at the Icahn School of Medicine.
Other leaders of the research team that screened the genetic factors to find the right combination included Kateri Moore, DVM, Associate Professor of Developmental and Regenerative Biology at the Icahn School and Ihor R. Lemischka, PhD, Professor of Developmental and Regenerative Biology, Pharmacology and Systems Therapeutics and Director of The Black Family Stem Cell Institute at The Mount Sinai Medical Center.
"The combination of gene factors that we used was not composed entirely of the most obvious or expected proteins," said Dr. Lemischka. "Many investigators have been trying to grow hematopoietic stem cells from embryonic stem cells, but this process has been problematic. Instead, we used mature mouse fibroblasts, picked the right combination of proteins, and it worked."
"This discovery is just the beginning of something new and exciting and can hopefully be used to identify a treatment for blood disorders," said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai and Executive Vice President for Academic Affairs at The Mount Sinai Medical Center.
According to Dr. Pereira, there is a critical shortage of suitable donors for blood stem cell transplants. Donors are currently necessary to meet the needs of patients suffering from blood diseases such as leukemia, aplastic anemia, lymphomas, multiple myeloma and immune deficiency disorders. "Programming of hematopoietic stem cells represents an exciting alternative," said Pereira.
"Dr. Lemischka and I have been working together for over 20 years in the fields of hematopoiesis and stem cell biology," said Dr. Moore, senior author of the study. "It is truly exciting to be able to grow these blood forming cells in a culture dish and learn so much from them. We have already started applying this new approach to human cells and anticipate similar success."
Mount Sinai Innovation Partners is managing the intellectual property for this cell replacement technology on behalf of the Mount Sinai researchers and is actively engaged with commercial collaboration opportunities.
About Mount Sinai Innovation Partners
Mount Sinai Innovation Partners (Mount Sinai IP), as part of the Icahn School of Medicine at Mount Sinai, facilitates the transfer of discovery from the laboratory to the marketplace, acting as the interface with commercial entities.
Mount Sinai IP is responsible for the full spectrum of commercialization activities required to bring the Icahn School of Medicine's inventions to life. These activities include evaluating, patenting, marketing, and licensing new technologies, while also negotiating agreements for sponsored research, material transfer, and confidentiality. Blue Mountain Technologies is an IP program to enhance distribution of, and product development based on, Mount Sinai's growing portfolio of novel reagents, diagnostics, and therapeutics. For more information on Mount Sinai IP, visit: http://www.mountsinai.org/innovation
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
About the Cellular Therapy Laboratory
The new Cellular Therapy Laboratory completes phase one of a three part reconstruction project which includes a new Blood Bank as well as a new HLA Laboratory. The Cellular Therapy Laboratory is responsible for the processing, cryopreservation and storage of hematopoietic cellular products used in the treatment of leukemia, lymphoma, Hodgkin's disease, multiple myeloma and selected solid tumors. Our laboratory provides assistance with the infusion of cellular therapy products for both inpatients and outpatients undergoing autologous and/or allogeneic transplantation.
The new Class 10,000 environmentally controlled processing facility includes an anteroom and two processing suites equipped with Class 100 biological safety cabinets. This expansion will enable our laboratory to meet the growing demands of Mount Sinai's Bone Marrow and Stem Cell Transplantation Program which performs over 170 transplants a year. In addition, the laboratory also performs processing in support of clinical trials using cellular products for treatment of non-hematologic diseases.
Our laboratory is accredited by the Foundation for the Accreditation of Cellular Therapy (FACT), the American Association of Blood Banks (AABB), the College of American Pathologists (CAP), and the Clinical Laboratories Improvement Amendment (CLIA). We are registered with and inspected by the State of New York Department of Health and the Food and Drug Administration (FDA).
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and the Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members 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 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by 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.
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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 and the South Nassau Communities Hospital is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.