have found a way to produce increased numbers of blood cells from a patient's
existing cells through an improved stem
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
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
"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,"
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.