Mount Sinai researchers succeed in programming blood forming stem cells

Study is first step towards generating patient-specific blood products for cell-replacement therapy

2013-06-13

(Press-News.org) (New York, NY – June 13, 2013)--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 in CELL STEM CELL on June 13. 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 the Icahn School of Medicine is a pioneer in stem cell research.

About 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, and 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 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 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.

For more information, visit http://www.mountsinai.org. Find Mount Sinai on Facebook (http://www.facebook.com/mountsinainyc), Twitter (@mountsinainyc) and YouTube (http://www.youtube.com/mountsinainy). END

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Mount Sinai researchers succeed in programming blood forming stem cells

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