Hematopoietic blood cells from human pluripotent stem cells  (Source: Aaron Parker, Salk Institute for Biological Studies)
The technique still needs work, but the team identified blood-specific markers on 84 percent of the cells after three weeks, which is a large leap in efficiency compared to a few years ago

Researchers have found a way to produce increased numbers of blood cells from a patient's existing cells through an improved stem cell technique

Inder M. Verma, Ph.D., study leader and Irwin and Joan Jacobs Chair in Exemplary Life Science and American Cancer Society Professor of Molecular Biology at the Salk Institute Laboratory of Genetics, along with Aaron Parker, Ph.D., postdoctoral researcher in Verma's lab, and Niels-Bjarne Woods, Ph.D., a former postdoctoral student in Verma's lab, have created a technique that could eventually be used in a number of stem cell therapies for conditions like cancer. 

Scientists first turned human skin cells into induced pluripotent stem cells (iPSCs) in 2006. These iPSCs imitated embryonic stem cell (ESCs), which are what organisms develop from. This discovery has prompted many other researchers to experiment with different sequences and mixes of the chemical compounds that cause iPSCs to mature into certain "tissue-specific stem cells." While scientific studies have been able to use stem cells to create new body parts and organs, this could not be done with high efficiency. 

Verma and the team have been trying to find an efficient way of turning iPSCs into hematopoietic stem cells (HSCs), which are capable of supplying oxygen-carrying red blood cells and white blood cells. Now, they've found a technique that allows ESCs to become HSCs in the womb. 

"We took seven lines of human ESCs and iPSCs, and experimented with different combinations and sequences of growth factors and other chemical compounds that are known to be present as ESCs move to the HSC state in a developing human," said Parker. 

The team was able to create colonies of cells that had the molecular markers of blood cells by inducing the iPSCs and ESCs through the application of "cocktails" of growth factors and other chemical compounds. According to their results, the best cocktail identified blood-specific markers on 84 percent of the cells after three weeks. Parker noted that this is huge progress in efficiency compared to a few years ago.

But the technique could still use some work. For instance, progenitor cells and mature cells were only identified from one lineage, which were myeloid cells. These cells include red blood cells and primitive immune cells. They couldn't find any cells like T-cells and B-cells from the lymphoid lineage. In addition, the blood cells they produced from iPSCs and ESCs had short-lived progenitors and mature blood cells but no transplantable HSCs. The team thinks this happened because the cocktail moved cells past the HSC state to the progenitor state, or skip the HSC state completely.

"There are further improvements we need to make, but this takes us a significant step closer to the ultimate goal, which is to be able to take ordinary cells from a patient, induce them to become stem cells, and then use those stem cells to rebuild lost or diseased tissues, for example the patient's bone marrow," said Verma. 

Parker added that the team will now focus on identifying maturation signs provided in a specific region of mammals where HSCs appear during embryonic development, and will use this information to produce transplantable HSCs. Then, they will test the therapy on human patients.

"But we're now tantalizingly close to our ultimate goal," said Verma. 

This study was published in Stem Cells.

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