316
Cell Growth in Microgravity
environment of the MACS were more
similar in composition and mechanical
strength to natural cartilage. This experi-
ment demonstrated the microgravity effect
on cellular functions and processes in the
synthesis, secretion, and assembly of ex-
tracellular matrix proteins. It is known
that microgravity exerts deleterious effects
on existing cartilage and bone. This in-
vestigation demonstrated the effect that
microgravity may have on remodeling
of tissues such as cartilage. Earth-grown
constructs in the analog culture were
superior to the flight effects of 1
g
.Sub
-
sequent experiments should delineate the
effects of
g
forces on the process of tissue
morphogenesis.
Space cell culture may not offer ad-
vantages in tissue morphogenesis for all
cell types. Experiments with osteoblasts
(i.e. bone-forming cells) were performed
on STS-56 to assess the gene expression
changes that occurred in microgravity.
The results were that prostaglandin syn-
thesis did occur during space flight and
there were signiFcant changes in cellular
morphology and the acting cytoskeleton.
Additionally, there was reduced growth
of osteoblasts after four days in micro-
gravity. ±ollowing this, a series of exper-
iments on the European Space Agency
Biorack (STS-76, STS-81, and STS-84) were
performed on osteoblasts using ground
and in-flight 1
g
controls. The expres-
sion of immediate early genes such as
c-
fos
,and
cox-2
was altered signiFcantly
in microgravity. However, osteoblast F-
bronectin mRNA, protein synthesis, and
matrix remained unchanged after expo-
sure to microgravity. This suggests the
possibility of altered signaling in the os-
teoblast, since the expression of these
genes is critical for gene transcription and
cell activation. The aggregation and se-
cretion of bioactive products in MIP101
colon
carcinoma
cells
were
enhanced
in
microgravity.
The
extent
of
aggre-
gation, proliferation, and differentiation
of PC 12 pheochromocytoma (neoplastic
adrenomedullary) cells in space was also
enhanced. In addition, the rate of glucose
consumption was Fve times higher than
in ground cultures.
Primary cultures of human cortical re-
nal epithelial cells were flown on the space
shuttle to test the hypothesis that the adap-
tation of cells to conditions in space is
reflected in the changes in gene expres-
sion. Cells in microgravity and ground-
based controls were grown for six days
and Fxed. RNA was extracted, and auto-
mated gene array analysis of the expression
of 10 000 genes was performed. A se-
lect group of 1632 genes was regulated
in microgravity. The magnitude of the
response signiFes that the conditions in
spaceflight offer a multitude of perturba-
tions to the cells and some of the motifs
are coincident with known response suites.
These were consistent with shear stress re-
sponse genes and heat shock proteins. In
other instances, there are gene expression
changes that may be reflective of novel
suites that may be related to micrograv-
ity, culture conditions, and changes in
other forces such as convection. ±inally,
some are most likely related to the pro-
motion of tissue morphogenesis. These
included the Wilm’s tumor zinc Fnger pro-
tein and the vitamin D receptor expressed
in space cultures of differentiated renal
cortical cells.
6
Conclusions
Microgravity thus affects cells in different
ways. In bone and muscle systems, mi-
crogravity exposure results in inhibition
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