Bryan S. Margulies

Bryan S. Margulies

Jan 20, 2015

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What cells are present in the bone marrow surrounding failing total joint implants?

Final post of what happens to the cells, osteoclasts, that normally degrade bone and have been hypothesized to degrade bone at an accelerated rate in a failing join implant. These figures are all derived from tissue taken from next to a failing hip or knee implant. One alternative fate for the progenitor cells are one of two types of macrophage: the M1- or M2-macrophage. M1-macrophages regulate inflammation while M2-macrophages regulate tissue repair and the recruitment of new blood vessels. The top panels (A-C) show markers that stain M2-macrophages: CD14, Arganase-1 (Arg1) and CD206. CD14, Arg1 and CD206 are stained red while MHCII-receptor (TL) is stained green with a protein derived from tomatoes (tomato lectin). Cell nuclei are stained blue. (D-F) In contrast, the markers for the the M1-macrophage are not present as shown by the predominantly green TL staining.

The progenitor cells for the M1- and M2-macrophages as well as the osteoclast are abundant in the bone marrow, which surrounds the total joint implant. An alternative to having too many osteoclasts that degrade too much bone in a failing implant would be pro-inflammatory M1-macrphage activity. However, we did not observe M1-macrophages. We did observe M2-macrophages, which play no role in degrading bone. Interestingly, the IL6 expressed by mesenchymal stem cells promotes the formation of M2-macrophages.

Our data presents a scenario in which mesenchymal stem cells produce factors (IL6 and OPG) that promote the formation of M2-macrophages. Since bone degradation must occur for bone to remain healthy, the loss of the normal process of bone degradation may result in pathologic bone. What we don't know currently is what effect the M2-macrophages have on the mesenchymal stem cells. To understand the potential effects that the M2-macrophages have on mesenchymal stem cells we will need to look at isolated populations of the MSC, which is the focus of this proposal.


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About This Project

We study a special group of Stem Cells that reside in the Bone Marrow called mesenchymal stem cells (MSC). We believe that the MSC are deficient in patients with a failing hip or knee implant. We hope that a close examination of these stem cells will allow us to develop therapies that could prolong the life of a failing implant.

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