Heterogeneous Differentiation of Human Mesenchymal Stem Cells in Response to Extended Culture in Extracellular Matrices
Overview
Biomedical Engineering
Biotechnology
Affiliations
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.
Driving mesenchymal stem cell differentiation from self-assembled monolayers.
Tew L, Ching J, Ngalim S, Khung Y RSC Adv. 2022; 8(12):6551-6564.
PMID: 35540392 PMC: 9078311. DOI: 10.1039/c7ra12234a.
Bruschi M, Sahu N, Singla M, Grandi F, Agarwal P, Chu C Tissue Eng Part A. 2021; 28(9-10):433-446.
PMID: 34693750 PMC: 9131357. DOI: 10.1089/ten.TEA.2021.0172.
Kinases of the Focal Adhesion Complex Contribute to Cardiomyocyte Specification.
Robert S, Flowers M, Ogle B Int J Mol Sci. 2021; 22(19).
PMID: 34638793 PMC: 8508671. DOI: 10.3390/ijms221910430.
Single-Cell Transcriptome Analysis as a Promising Tool to Study Pluripotent Stem Cell Reprogramming.
Kim H, Ha T, Lee M Int J Mol Sci. 2021; 22(11).
PMID: 34206025 PMC: 8198005. DOI: 10.3390/ijms22115988.
Xiong X, Yang X, Dai H, Feng G, Zhang Y, Zhou J Stem Cell Res Ther. 2019; 10(1):396.
PMID: 31852539 PMC: 6921428. DOI: 10.1186/s13287-019-1483-7.