The secretome of stem cells strongly determines the outcome of tissue engineering strategies. We investigated how the secretome
of human adipose stem cells (hASCs) can be affected by substrate, BMP-2 treatment, and degree of differentiation. We hypothesized
that as differentiation progresses, hASCs produce increasingly more gene products associated with processes such as angiogenesis
and bone remodeling.
Human ASCs were treated for 15 min with BMP-2 (10 ng/ml) to enhance osteogenic differentiation,
or with vehicle. Subsequently, hASCs were seeded on plastic or on biphasic calcium phosphate (BCP) consisting of 60% hydroxyapatite
and 40% β-tricalcium phosphate. A PCR array for ∼150 trophic factors and differentiation-related genes was performed at day
21 of culture. A limited set of factors was quantified by qPCR at days 0, 4, 14 and 21, and/or ELISA at day 21.
to plastic, BCP-cultured hASCs showed ≥2-fold higher expression of ∼20 factors, e.g. cytokines such as IL-6, growth factors
such as FGF7 and adhesion molecules such as VCAM1. Expression of another ∼50 genes was decreased ≥2-fold on BCP vs. plastic,
even though hASCs differentiate better on BCP than on plastic. BMP-2-treatment increased the expression of ∼30 factors by
hASCs seeded on BCP, while it decreased the expression of only PGF, PPARG and PTN. Substrate affected hASC secretion of Activin
A and seemed to affect P1NP release. No clear association between hASC osteogenic differentiation and growth factor expression
pattern was observed.
Considering our observed lack of association between the degree of differentiation and the
expression of factors associated with angiogenesis and bone remodeling by hASCs, future bone regeneration studies should focus
more on systematically orchestrating the secretome of stem cells, rather than on inducing osteogenic differentiation of stem
cells only. Short incubation with BMP-2 may be a promising treatment to enhance both osteogenic differentiation and environmental