Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
Scientific Community
Become a Member | Sign in
Home>News>This Article

Scientists Revert Mature Blood Cells into Blood-Forming Stem Cells

Published: Tuesday, May 27, 2014
Last Updated: Tuesday, May 27, 2014
Bookmark and Share
Discovery opens new possibilities for regenerative medicine.

Harvard Stem Cell Institute researchers at Boston Children’s Hospital have reprogrammed mature blood cells from mice into blood-forming hematopoietic stem cells (HSCs) using a cocktail of eight genetic switches called transcription factors. The reprogrammed cells, which the researchers have dubbed induced HSCs (iHSCs), have the functional hallmarks of HSCs, are able to self-renew like HSCs, and can give rise to all of the cellular components of the blood like HSCs.

The findings mark a significant step toward one of the most sought-after goals of regenerative medicine: the ability to produce HSCs suitable for transplantation using more mature or differentiated cells. Blood stem cell transplants (also known as bone marrow transplants) have been saving the lives of patients for almost three decades, but have been limited by the difficulty of obtaining good cell matches for transplantation.

The work, reported online in the journal Cell, was led by Harvard Stem Cell Institute Principal Faculty member Derrick J. Rossi, PhD, of Boston Children's Program in Cellular and Molecular Medicine.

HSCs are the basic starting material for all blood stem cell transplants, regardless of their source (bone marrow, umbilical cord blood, peripheral blood). The success of any individual patient's transplant correlates with the number of HSCs available for transplant: the more cells, the more likely the transplant will take hold. However, HSCs are quite rare.

"HSCs only comprise about 1 in every 20,000 cells in the bone marrow," Rossi said. "If we could generate HSCs from a patient's other cells, it could be transformative for transplant medicine and for our ability to model diseases of blood development."

In their study, Rossi and his collaborators, including lead author Jonah Riddell, PhD, screened gene expression in 40 different types of blood and blood progenitor cells from mice. From this screen they identified 36 transcription factors-genes that control when other genes are turned on and off-that are expressed exclusively in HSCs, not in cells that arise from them.

"Blood cell production invariably goes in one direction: from stem cells, to progenitors, to mature effector cells,” Rossi explained. "We wanted to reverse the process and derive HSCs from differentiated blood cells using transcription factors that we found were specific to HSCs."

In a series of mouse transplantation experiments, Rossi's team found that six-Hlf, Runx1t1, Pbx1, Lmo2, Zfp37, and Prdm5—of the 36 factors, plus two additional factors not originally identified in their screen-Mycn and Meis1-were sufficient to robustly reprogram two kinds of blood progenitor cells (pro/pre B cells and common myeloid progenitor cells) into iHSCs.

Rossi's team reprogrammed their source cells by exposing them to viruses containing the genes for all eight factors and a molecular switch that turned the factor genes on in the presence of doxycycline. They then transplanted the exposed cells into recipient mice and activated the genes by giving the mice doxycycline. The resulting iHSCs were capable of generating the entire blood cell repertoire in the transplanted mice, showing that they had gained the ability to differentiate into all blood lineages.

Harvard Stem Cell Institute Principal; Faculty member Stuart Orkin, MD, one of the leaders of Dana-Farber/Boston Children's Cancer and Blood Disorders Center and a co-author on the paper, noted that the use of mice as a kind of reactor for reprogramming marks a novel direction in HSC research.

"In the blood research field no one has the conditions to expand HSCs in the tissue culture dish," he said. "By transplanting the virally exposed cells into mice, Derrick took advantage of the signaling and environmental cues HSCs would normally experience." Orkin added that iHSCs are nearly indistinguishable from normal HSCs at the transcriptional level.

As they stand, the findings are far from being translated to the transplantation clinic. Still to be answered are the precise contribution of each of the eight factors to the reprogramming process and whether approaches that do not rely on viruses and transcription factors can have similar success. It is also not yet known whether the same results can be achieved using human cells or whether other, non-blood cells can be reprogrammed to iHSCs.

"This discovery could have a radical effect on transplantation," Orkin said. "You could have gene-matched donors, you could use a patient's own cells to create iHSCs. It's a long way off, but this is a good step in the right direction."

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Vital Genes in Fat Production Found
Discovery could help researchers increase ‘good fat’ in patients, reduce ‘bad’.
Wednesday, June 17, 2015
New Strategy To Improve Stem Cell Transplantation
Research addresses hurdles to future transplant-based, gene-editing therapies that could help people with genetic blood diseases.
Thursday, November 20, 2014
Reprogramming Cells, Long Term
Positive finding could have major implications for diabetes treatment.
Wednesday, November 19, 2014
A Promising Strategy Against HIV
Harvard researchers genetically ‘edit’ human blood stem cells.
Saturday, November 08, 2014
From Stem Cells to Billions of Human Insulin-producing Cells
Giant step toward new diabetes treatment.
Friday, October 17, 2014
Herpes-loaded Stem Cells Used to Kill Brain Tumors
Scientists have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses.
Friday, May 16, 2014
New Possibilities for Regenerative Medicine
Harvard Stem Cell Institute researchers revert mature blood cells into blood-forming stem cells.
Friday, April 25, 2014
iPS Cells from Patients with Rare Disorder Shed Light on Aging and Cancer
HSCI investigators have used genetic reprogramming to create cells from patients with a rare premature-aging disorder that are able to rebuild their telomeres.
Monday, March 22, 2010
Discredited Korean Embryonic Stem Cells' True Origins Revealed
DNA analysis finds they were the world's first human embryonic stem cells derived from eggs alone.
Monday, August 06, 2007
Scientific News
Shining Light on Microbial Growth and Death Inside our Guts
Precise measurement of microbial populations in gastrointestinal tracts could be key to identifying novel therapies.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Fat Cells Originating from Bone Marrow Found in Humans
Cells could contribute to diabetes, heart disease.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
CRI Identifies Emergency Blood-formation Response
Researchers report that when tissue damage occurs, an emergency blood-formation system activates.
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
Promise of Newborn Stem Cells to Revolutionize Clinical Practice
In this article Shweta Sharma, PhD, discusses the potential of an Umbilical Cord Blood bank as an untapped source of samples for research and clinical trials.
The Life Story of Stem Cells
A model analyses the development of stem cell numbers in the human body.
Novel Stem Cell Line Avoids Risk of Introducing Transplanted Tumors
Progenitor cells might eventually be used to repair or rebuild damaged or destroyed organs.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos