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Genomic Analysis of Invasive Human Bone Marrow Derived Mesenchymal Stem Cells

Lesley A Mathews, Elaine M Hurt, Xiaohu Zhang and William L Farrar

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.