Stem cells—unspecialized cells that
have the potential to develop into different types of cells—play an important
role in medical research. In the embryotic stage of an organism’s growth, stem
cells develop into specialized heart, lung, and skin cells, among others; in
adults, they can act as repairmen, replacing cells that have been damaged by
injury, disease, or simply by age. Given their enormous potential in future
treatments against disease, the study and growth of stem cells in the laboratory
is widespread and critical. But growing the cells in culture offers numerous
challenges, including the constant need to replenish a culture medium to
support the desired cell growth.
Tarek Fahmy, associate professor of
biomedical engineering and chemical and environmental engineering at Yale
University, and colleagues have developed a nanoparticle-based system to
deliver growth factors to stem cells in culture. These growth factors, which
directly affect the growth of stem cells and their differentiation into
specific cell types, are ordinarily supplied in a medium that is exchanged
every day. Using the researchers’ new approach, this would no longer be necessary.
“Irrespective of their scale or
nature, all cell culture systems currently in practice conventionally supply
exogenous bioactive factors by direct addition to the culture medium,” says
Paul de Sousa, a University of Edinburgh researcher and co-PI on the paper.
With that approach, he explains, “Cost is one issue, especially during
prolonged culture and when there is a requirement for complex cocktails of
factors to expand or direct differentiation of cells to a specific endpoint.”
A second issue, says de Sousa, is
specificity: Growth factors supplied by direct addition to the culture medium
can lead to the growth of undesired cell populations, which can end up
competing with the growth of the desired cell types.
“A relatively unexplored strategy to
improve the efficiency of stem cell culture is to affinity-target critical
bioactive factors sequestered in biodegradable micro- or nanoparticles to cell
types of interest,” explains de Sousa, “thereby achieving a spatially and
temporally controlled local ‘paracrine’ stimulation of cells.”
Fahmy and his colleagues packaged
leukemia inhibitory factor, which supports stem cell growth and viability,
inside biodegradable nanoparticles. The nanoparticles were “targeted” by
attaching an antibody—one specific to an antigen on the surface of mouse
embryonic stem cells being grown in culture. As a result, the nanoparticles
target and attach themselves to the stem cells, ensuring direct delivery of the
bioactive factors packaged inside.
The researchers have previously
demonstrated the potential uses of this approach in drug delivery and
vaccination, including targeted delivery of leukocyte inhibitory factor (LIF),
which prevents certain types of white blood cells from migrating, in order to
regular immune responses. In stem cell cultures, LIF is also the key factor
required to keep the cells alive and let them retain their ability to develop
into specialized types of cells.
In this research, Fahmy and his
colleagues packed LIF into the biodegradable nanoparticles for slow-release
delivery to the stem cells in culture. Their results showed cell colony growth
with a 10,000-fold lower dose of LIF when using the nanoparticle-based delivery
system compared to traditional methods using soluble LIF in a growth medium.
While a stem cell culture sustained using a traditional method of exchanging
growth medium consumes as much as 25 ng of LIF in a day—about 875 ng after five
weeks of culture—only 0.05 total nanograms of LIF would be required to achieve
the same level of growth using the nanoparticle delivery system, a remarkable
reduction in the required materials.
The next step is to use these
systems with human cells to direct their differentiation into hematopoietic
cells—blood products. Clinical and industrial translation of this ability
requires efficient and cost effective strategies for cell manufacturing. In
principle, this method offers a means to produce standardized or individually
tailored cells to overcome challenges associated with donated blood products.
The work is described in Biomaterials.
Source: Yale University
