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Human ESCs form functional blood vessels in mice
Thursday,
08 March 2007
A group at Harvard Stem Cell Institute and Shanghai Huashan Hospital have
successfully shown that human embryonic stem cells can be induced to form
fully functional blood vessels in immunorestricted mice. Their work is
described in the February 25th issue of Nature Biotechnology.
Undifferentiated hESCs were induced to differentiate in either 2D
(monolayer) or 3D (embryoid bodies, EB) cultures in for 10 days. The
CD34+ cells were isolated, and cultured in the presence of angiogenic
(VEGF and FGF-2) or hematopoietic growth factors (SCF and Flt3L) or both
for an additional 7 to 10 days for endothelial and hematopoietic
differentiation.
The human ES
cell-derived CD34+ cells were then further cultured in a 3D-matrix made
of collagen for one day. A skin puncher was then used to create circular
disk-shape pieces of partially differentiated hES cells, and implanted
into the SCID mice, where they were let to grow and develop functional
bloodvessels.
Multiphoton laser-scanning microscopy was used
to visualize and quantify the morphological changes of green fluorescent
protein-expressing hESC-derived endothelial cells, and that the vessels were perfused was highlighted by tail vein injection of rhodamine-labeled dextran. The results show the
formation of functional engineered blood vessels.
The authors claim the differentiated cells contributed
to arborized blood vessels that integrated into the host circulatory
system and served as blood conduits for 150 d, which is a large part of a
mouse life-span.
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