Would
you please describe the significance of your paper and why it is highly
cited?
Human embryonic stem cells (hESCs) are considered not only a
research model into pathways of cell pluripotency (the ability to
differentiate into multiple cell types) during development but also
promising cell sources for regenerative medicine and drug testing.
These applications require reliable maintenance and propagation of
hESCs in the undifferentiated state.
|
“hESC-based
regenerative medicine holds great promise in
improving and enhancing human health.”
|
|
Previously, culturing undifferentiated hESCs had routinely been
carried out with mouse embryonic fibroblast feeders (MEFs) or MEF-conditioned
medium (MEF-CM) in combination with extracellular matrix. Because of
the complex and poorly understood nature of the factors produced by
MEFs, these methods are liable to contribute to variability in the
quality of hESCs, raise the risk of transmitting pathogens, and
potentially cause increased immunogenicity.
In our paper, we report that basic fibroblast growth factor (bFGF)
at high concentrations, either alone or in combination with other
factors, is able to maintain undifferentiated hESCs in long-term
cultures without conditioned media or feeders. We show that hESCs
thus maintained are similar to the MEF-CM cultures in their
expression of undifferentiated cell markers, telomerase activity,
karyotypic stability, and differentiation capacity.
Our finding highlights a critical role of bFGF in stem cell
self-renewal and introduces a more simplified method of maintaining
hESCs. We consider both the mechanistic implication and practical
application as the appeal for other researchers to cite our paper.
How
did you become involved in this research, and were there any particular
successes or obstacles that stand out?
We at Geron are interested in the development of hESC-based
therapeutics and have been carrying out a series of experiments
optimizing hESC culture methods. We made a significant improvement
in hESC culture by first developing a feeder-free culture system,
where cells can be maintained on matrix proteins with MEF-CM
(reported in Xu et al., Nat. Biotechnol. 22: 707-716,
2001).
As conditioned media are complex, difficult to qualify, and
inherently unsuitable for therapeutic applications, we wanted to
identify factors that would permit self-renewal of hESCs in the
absence of the conditioned medium. That led us to discover the
utility of bFGF from amongst many candidate factors.
Where
do you see your research and the broader field leading in the future?
Translational research will require thorough understanding of
fundamental stem cell biology and development of more defined, safe,
and scalable methods to expand undifferentiated hESCs and
differentiate into specific, clinically efficacious cell types.
What
are the social implications of your work?
hESC-based regenerative medicine holds great promise in improving
and enhancing human health. Developing methods such as ours not only
contributes to further understanding of the molecular control of
undifferentiated hESC expansion but also facilitates the operational
use of these cells in potential routine clinical practice.
Chunhui Xu, Ph.D.
Department of Cell Biology
Geron Corporation
Menlo Park, CA, USA
n
the interview below, Dr. Chunhui Xu talks with us about her
highly cited paper, "Basic fibroblast growth factor supports
undifferentiated human embryonic stem cell growth without
conditioned medium," (Xu et al., Stem Cells 23[3]:
315-23, March 2005), which is a part of the
