Genomic Analysis of Invasive Human Bone Marrow Derived Mesenchymal Stem Cells.

Background: Human bone marrow derived mesenchymal stem cells (hMSCs) are capable of differentiation into multiple cell lineages and demonstrate a wide variety of use in various therapeutic applications. Only recently has research begun to understand the gene expression profiles of hMSCs and their differentiated counterparts in vivo and ex vivo .
Purpose: The research presented here aimed at gaining a better understanding of gene expression patterns present during hMSC invasion through a basement membrane.
Methods: Changes in gene expression were evaluated between invasive and non-invasive cells using Agilent's gene expression arrays and Matrigel invasion chambers. The cells were specifically attracted to a defined stem cell media called SCM.
Results: A total 435 genes were up-regulated by 2- fold or more in the invasive population of cells and classified into developmental programs and immunological/inflammatory signaling pathways determined by Ingenuity Pathway Analysis (IPA). This list included a variety of regulators of growth and differentiation including NANOG, STAT3 and STAT5A and members of the polycomb repressive complex-2 (PCRC2) EZH2 and SUZ12. The known regulator of inflammation and hypoxia HIF-1α was also increased suggesting that regulation of the microenvironment is important during this process. Finally, the invasion process could be reversed using the STAT3 inhibitor Static.
Conclusions: Overall these data will increase the understanding of the genetic pathways functioning during hMSC invasion and aid in the development of their therapeutic applications.