Blood factories closer to reality

November 30, 2018, Agency for Science, Technology and Research (A*STAR), Singapore
A*STAR researchers are getting close to growing huge numbers of red blood cells in industrial-grade vats. Credit: Bioprocessing Technology Institute

Blood cells grown in large vats from a starter stock of stem cells could one day supplement or even replace blood taken from human donors. However, existing protocols for making red blood cells (RBCs) in the lab can't be easily scaled up to produce the volumes needed to meet demand.

Now, A*STAR scientists have optimized the molecular recipes and growth-supporting microparticles needed to prepare and sustain billions of stem cell-derived RBCs in industrial-scale manufacturing vessels known as bioreactors. They have shown that transient activation of a key signaling pathway can dramatically boost efficiencies across a range of starting materials.

The system is still nowhere near producing the 1–2 trillion RBCs found in each 'unit' of donated —but it's getting close. And soon, Jaichandran Sivalingam, a research scientist at A*STAR's Bioprocessing Technology Institute (BTI), expects the platform to help solve the dual problem of supply shortages and transmissible infections that undermine transfusion medicine.

Jaichandran and his colleagues from Steve Oh's Stem Cell Bioprocessing research group previously developed a system for transforming induced into RBC precursors under the kinds of conditions needed to keep enormous numbers of alive and healthy. The technique worked, but it wasn't very robust. When applied to multiple stem cell lines, the , which included collaborators from Jonathan Loh's group at the A*STAR Institute of Molecular and Cell Biology, recorded wildly different RBC differentiation efficiencies.

To find out why, the researchers searched for factors that enhanced the first step of the differentiation process. They found that a drug activator of the Wnt/β-catenin pathway, which regulates cell fate decisions, helped coax the reprogrammed into forming early blood progenitors. They added this drug to their protocol and produced up to 60,000 blood precursor cells from each stem cell within about 50 days in culture—a 40-fold improvement over the team's prior approach.

There are still hurdles the method needs to overcome. The system, which was described recently in the journal Haematologica1, used a semi-solid, gelatinous growth medium, "which would be challenging for scale-up," Jaichandran explains. Since the paper came out, though, "we have made significant improvements," he says, and the A*STAR scientists can now produce around 1.5 billion blood precursor cells in a flask about as large as a travel-sized shampoo bottle.

Next up, says Jaichandran, will be full-capacity, liter-sized tanks. "We are working to achieve ultra-high density cultures of RBCs in controlled bioreactors."

Explore further: Red blood cells derived from stem cells could offer a limitless supply for transfusions

More information: Jaichandran Sivalingam et al. Improved erythroid differentiation of multiple human pluripotent stem cell lines in microcarrier culture by modulation of Wnt/β-Catenin signaling, Haematologica (2018). DOI: 10.3324/haematol.2017.180919

Related Stories

Red blood cells derived from stem cells could offer a limitless supply for transfusions

April 19, 2017
As the Singapore Red Cross says, the need for blood never stops. But the demand for blood from living donors could become a thing of the past, as A*STAR researchers make red blood cells (RBCs) from stem cells in an efficient ...

Some blood stem cells are better than others

May 30, 2018
In your body, blood stem cells produce approximately 10 billion new white blood cells, which are also known as immune cells, each and every day. Even more remarkably, if some of these blood stem cells fail to do their part, ...

Generating large numbers of universal immune cells could transform cancer immunotherapy

May 16, 2018
A scalable method of generating universal 'off-the-shelf' natural killer (NK) cells for cancer immunotherapies has been devised by A*STAR researchers. Their technique could ensure that future NK cell-based cancer treatments ...

How blood can be rejuvenated

February 23, 2017
Our blood stem cells generate around a thousand billion new blood cells every day. But the blood stem cells' capacity to produce blood changes as we age. This leads to older people being more susceptible to anaemia, lowered ...

Recommended for you

New light-based technology reveals how cells communicate in human disease

December 11, 2018
Scientists at the University of York have developed a new technique that uses light to understand how cells communicate in human disease.

Study may offer doctors a more effective way to treat neuroblastoma

December 7, 2018
A very large team of researchers, mostly from multiple institutions across Germany, has found what might be a better way to treat patients with neuroblastoma, a type of cancer. In their paper published in the journal Science, ...

Progress made in transplanting pig hearts into baboons

December 6, 2018
A large team of researchers from several institutions in Germany, Sweden, Switzerland and the U.S. has transplanted pig hearts into baboons and kept them alive for an extended period of time. In their paper published in the ...

'Chemo brain' caused by malfunction in three types of brain cells, study finds

December 6, 2018
More than half of cancer survivors suffer from cognitive impairment from chemotherapy that lingers for months or years after the cancer is gone. In a new study explaining the cellular mechanisms behind this condition, scientists ...

Hybrid prevalence estimation: Method to improve intervention coverage estimations

December 6, 2018
LSTM's Professor Joseph Valadez is senior author on a new study published today in the Proceedings of the National Academy of Sciences, which outlines proposals for a more accurate estimator of health data.

World's smallest wearable device warns of UV exposure, enables precision phototherapy

December 5, 2018
The world's smallest wearable, battery-free device has been developed by Northwestern Medicine and Northwestern's McCormick School of Engineering scientists to measure exposure to light across multiple wavelengths, from the ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.