Abstract

Within the Regenerative Medicine Institute, my laboratory is interested in some of the basic biology of mesenchymal stem cells (MSC).

MSC generally reside in a relatively hypoxic environment within the bone marrow or in tumors. Enigmatically, MSC are known to both support hematopoiesis, particularly early lymphopoiesis, yet are also capable of inhibiting the function of mature lymphocytes.

Starting with a collection of non-transformed MSC lines, we have shown that despite their prolonged culture history, they have retained physiological responsiveness to hypoxia. They are very resistant to DNA damage mediated by X-irradiation and have an extremely efficient DNA damage response (DDR). Indeed, recent data indicates that hypoxia improves the DDR of MSC in a HIF -1-dependent fashion 1.

To extend these studies, we have begun analyzing the extracellular matrix (ECM) produced by these cells. Preliminary data indicates that ECM derived from MSC lines cultured in hypoxia increases transcripts for stem cell genes in MSC and has potent biological activity on MSC growth and differentiation.

We are using this information to design culture systems to improve the clonal growth of mouse MSC freshly sorted from the bone marrow. Some of the implications of these results will be discussed.


1 Sugrue T, Lowndes NF and Ceredig R. Hypoxia enhances the radio-resistance of mouse mesenchymal stromal cells. Stem Cells, 2014 32:2188-200