60 THE SCIENTIST | the-scientist.com
LAB TOOLSANDREW STEWART, MINERVA BIOTECHNOLOGIESC
ell biologist Alicia Lyle hoped to
use mouse mesenchymal stem cells
to deliver molecular cargos to tis-
sues, and she also wanted to study how
MSCs from different lines of knockout
mice assemble into blood vessels. But Lyle’s
group, at Emory University in Atlanta, soon
hit a snag: growing the cells took ages.
“Even with the tenderest of care, it was
taking somewhere close to eight to twelve
weeks to even reach a point... to passage
them,” recalls Lyle, referring to the point
when cells crowd a dish and need to be split
between multiple culture flasks. And by
passage seven or eight, Lyle’s cells began to
senesce, losing their ability to either main-
tain pluripotency or differentiate.
While mouse MSCs are particularly dif-
ficult to work with, Lyle’s complaints echo
those heard across the stem cell field. To
both understand stem cells and use them to
treat diseases, efficiency will be crucial. “We
want to harness that power of stem cells, we
want to use it to treat patients, but then you
are limited by how many you can make,”
laments Abba Zubair, medical director for
transfusion medicine and the Human Cell
Therapy Laboratory at the Mayo Clinic in
Jacksonville, Florida. No one wants to wait
around for months while stem cells grow, or
discover that only a few have the potential
to differentiate as desired.
And stem cell treatments will only
become affordable and commonplace if
the technical processes used to develop
them are efficient. For now, another type
of cell therapy, the first approved CAR
T-cell treatment for cancer, Novartis’s
Kymriah, costs $475,000 for a single dose,
suggesting that stem cell–based treat-
ments using today’s protocols will be simi-
larly complicated and expensive. Still, the
potential demand for stem cells could be
quite high, both to directly treat patientsand for research into future treatments.
To screen 1 million drugs would require
on the order of 100 billion stem cells, as
would building a human heart or liver
from scratch.How can scientists speed things up?
Every stem cell type, from embryonic to
induced pluripotent to tissue-specific,
has its ow n particular requirements for
healthy, optimal growth and differen-
tiation. But there are a few general tips
that all stem cell researchers can employ.
Some scientists obtain good results by try-
ing different growth factors. One particu-
lar recombinant growth factor, NME7AB,
which supports cells in their most naïve,
pluripotent state, can streamline experi-
ments. Another tactic is to develop stem
cell-nurturing, three-dimensional culturetechniques, such as a new approach that
encases cells in long, sausage-like tubes.
And experimentalists can also improve
their stem cell quality and yields by com-
bining more than one method.
Overall, what seems to work is to pro-
vide a cell culture setting that mimics the
natural stem-cell niche as closely as pos-
sible, which minimizes cell stress, advises
Yuguo Lei, a biomedical engineer at the
University of Nebraska–Lincoln.EMBRACE NAÏVETÉ
Induced pluripotent stem cells (iPSCs),
made from a person’s blood or skin cells,
have become tremendously popular. But
Cynthia Bamdad, CEO of Minerva Bio-
technologies in Waltham, Massachusetts,
says most iPSC cultures are not as “stem”
as they could be.
The stem cells in the inner cell mass
of an embryo, known as naïve stem cells,Stem cell experts share their hard-won tips on making your cells grow faster,
healthier, and in higher numbers.BY AMBER DANCEThe Native Niche
THEY’VE GOT THE BEAT:Heart muscle cells
derived from human iPSCs with NME7AB in
the media form much more organized myofibrils,
needed for contraction, compared to those raised
in fibroblast growth factor 2 (FGF2).We want to harness the power
of stem cells... but you are
limited by how many you
can make.
—Abba Zubair, Mayo Clinic