TY - JOUR
T1 - Heterogeneous differentiation of human mesenchymal stem cells in response to extended culture in extracellular matrices
AU - Santiago, Jose A.
AU - Pogemiller, Ryan
AU - Ogle, Brenda M.
PY - 2009/12/1
Y1 - 2009/12/1
N2 - Extracellular matrix proteins (ECMs) guide differentiation of adult stem cells, but the temporal distribution of differentiation (i.e., heterogeneity) in a given population has not been investigated. We tested the effect of individual ECM proteins on lineage commitment of human bone marrow-derived mesenchymal stem cells (MSCs) over time. We exposed stem cell populations to ECM proteins representing the primary tissue structures of the body (i.e., collagens type I, III, IV; laminin; and fibronectin) and determined the lineage commitment of the stem cells at 1, 7, and 14 days. We found that collagens that can participate in the formation of fibrils guide differentiation of cardiomyocytes, adipocytes, and osteoblasts. ECMs of the basement membrane initiate differentiation of cardiomyocytes and osteoblasts but not adipocytes, and small facilitator ECMs (e.g., fibronectin) do not significantly affect stem cell differentiation. Differentiation was ECM-dependent because culture on tissue culture polystyrene, with consistent cell morphology, proliferation, and death, initiated differentiation of osteoblasts only. Thus, we show that ECMs independently trigger differentiation of human adult MSCs and that differentiation in this context can be guided down multiple lineages using the same ECM stimulus. This work highlights the importance of more clearly defining progenitor populations, especially those cultured in the presence of ECMs before transplantation.
AB - Extracellular matrix proteins (ECMs) guide differentiation of adult stem cells, but the temporal distribution of differentiation (i.e., heterogeneity) in a given population has not been investigated. We tested the effect of individual ECM proteins on lineage commitment of human bone marrow-derived mesenchymal stem cells (MSCs) over time. We exposed stem cell populations to ECM proteins representing the primary tissue structures of the body (i.e., collagens type I, III, IV; laminin; and fibronectin) and determined the lineage commitment of the stem cells at 1, 7, and 14 days. We found that collagens that can participate in the formation of fibrils guide differentiation of cardiomyocytes, adipocytes, and osteoblasts. ECMs of the basement membrane initiate differentiation of cardiomyocytes and osteoblasts but not adipocytes, and small facilitator ECMs (e.g., fibronectin) do not significantly affect stem cell differentiation. Differentiation was ECM-dependent because culture on tissue culture polystyrene, with consistent cell morphology, proliferation, and death, initiated differentiation of osteoblasts only. Thus, we show that ECMs independently trigger differentiation of human adult MSCs and that differentiation in this context can be guided down multiple lineages using the same ECM stimulus. This work highlights the importance of more clearly defining progenitor populations, especially those cultured in the presence of ECMs before transplantation.
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U2 - 10.1089/ten.tea.2008.0603
DO - 10.1089/ten.tea.2008.0603
M3 - Article
C2 - 19911955
AN - SCOPUS:72049102132
SN - 1937-3341
VL - 15
SP - 3911
EP - 3922
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
IS - 12
ER -