Nav: Home

Approaching a decades-old goal: Making blood stem cells from patients' own cells

May 17, 2017

Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance, published today in the journal Nature, opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived from patients' own cells.

"We're tantalizingly close to generating bona fide human blood stem cells in a dish," says senior investigator George Daley, MD, PhD, who heads a research lab in Boston Children's Hospital's Stem Cell Program and is dean of Harvard Medical School. "This work is the culmination of over 20 years of striving."

Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice.

"This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," says Ryohichi (Rio) Sugimura, MD, PhD, the study's first author and a postdoctoral fellow in the Daley Lab. "This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions."

Combining two approaches to achieve a breakthrough

Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells. In 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming. iPS cells were later used to generate multiple human cell types, such as neurons and heart cells -- yet blood-forming stem cells remained elusive.

Sugimura, Daley and colleagues combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialized cells and tissues during normal embryonic development. This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish.

In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood-forming state. Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells. They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy.

Finally, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation. These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination.

ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease.

"We're now able to model human blood function in so-called 'humanized mice,'" says Daley. "This is a major step forward for our ability to investigate genetic blood disease."

What is a blood stem cell?

The researchers' technique produced a mixture of blood stem cells and so-called hematopoietic progenitor cells, which also give rise to blood cells. Their ultimate goal is to expand their ability to make true blood stem cells in a way that's practical and safe, without the need for viruses to deliver the transcription factors, and to introduce gene-editing techniques like CRISPR to correct genetic defects in pluripotent stem cells before blood cells are made.

One challenge in making bona-fide human blood stem cells is that no one's been able to fully characterize these cells.

"It's proved challenging to 'see' these cells," says Sugimura. "You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can't go back and study it -- it's already gone. A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona-fide human blood stem cells."
-end-
The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R24DK092760), the National Institute of Allergy and Infectious Diseases (R37AI039394), the National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium (UO1-HL100001), Alex's Lemonade Stand, the Doris Duke Medical Foundation, the American Society of Hematology Scholar Fellowship and the Howard Hughes Medical Institute.

Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 415-bed comprehensive center for pediatric and adolescent health care. Boston Children's is also the primary pediatric teaching affiliate of Harvard Medical School. For more, visit our Vector and Thriving blogs and follow us on our social media channels: @BostonChildrens, @BCH_Innovation, Facebook and YouTube.

Boston Children's Hospital

Related Pluripotent Stem Cells Articles:

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.
Ultrastructure of focal adhesion scaffold unveiled in human pluripotent stem cells
Focal adhesions are known as signalling platforms broadcasting the information of the biochemical and physical qualities of the extracellular matrix into intracellular signalling cascades.
First generation of induced pluripotent stem cells from domestic cats
Researchers have reported for the first time producing feline induced pluripotent stem cells (fiPSCs) from adult cells of domestic cats.
Simple protocol for assessing maturation of HPCs from induced pluripotent stem cells
Researchers have developed a guide to help labs standardize the production of mature hepatic-like cells (HPCs) from stem cells and easily compare gene expression of HPCs to actual human liver tissue.
Researchers characterize 'mutational burden' of human induced pluripotent stem cells
In a new study, published in this week's issue of Cell Reports, researchers at the University of California San Diego School of Medicine scrutinized the whole genome sequences of 18 induced pluripotent stem cell lines derived from skin cells that they had reprogrammed to identify and characterize somatic mutations.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
An index measures similarity between cancer cells and pluripotent stem cells
The new methodology measures tumor aggressiveness and the risk of relapse, helping doctors plan treatment, according to Brazilian scientists authors of a paper published in a special issue of the journal Cell.
Induced pluripotent stem cells could serve as cancer vaccine, Stanford researchers say
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine.
Reproducing higher-order embryonic kidney structures using pluripotent stem cells
In the embryonic kidney, three types of precursor cells interact with each other to form a three-dimensional structure.
More Pluripotent Stem Cells News and Pluripotent Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.