New technique allows scientists to find rare stem cells within bone marrow

13 hours ago by Anne Trafton MIT and SMART researchers have developed a way to isolate mesenchymal stem cells based on physical traits such as stiffness. Credit: MIT

Deep within the bone marrow resides a type of cells known as mesenchymal stem cells (MSCs). These immature cells can differentiate into cells that produce bone, cartilage, fat, or musclea trait that scientists have tried to exploit for tissue repair.

In a new study that should make it easier to develop such stem-cell-based therapies, a team of researchers from MIT and the Singapore-MIT Alliance in Research and Technology (SMART) has identified three physical characteristics of MSCs that can distinguish them from other immature cells found in the bone marrow. Based on this information, they plan to create devices that could rapidly isolate MSCs, making it easier to generate enough stem cells to treat patients.

Until now, there has been no good way to separate MSCs from bone marrow cells that have already begun to differentiate into other cell types, but share the same molecules on the cell surface. This may be one reason why research results vary among labs, and why stem-cell treatments now in clinical trials are not as effective as they could be, says Krystyn Van Vliet, an MIT associate professor of materials science and engineering and biological engineering and a senior author of the paper, which appears in the Proceedings of the National Academy of Sciences this week.

"Some of the cells that you're putting in and calling stem cells are producing a beneficial therapeutic outcome, but many of the cells that you're putting in are not," Van Vliet says. "Our approach provides a way to purify or highly enrich for the stem cells in that population. You can now find the needles in the haystack and use them for human therapy."

Lead authors of the paper are W.C. Lee, a former graduate student at the National University of Singapore and SMART, and Hui Shi, a former SMART postdoc. Other authors are Jongyoon Han, an MIT professor of electrical engineering and biological engineering, SMART researchers Zhiyong Poon, L.M. Nyan, and Tanwi Kaushik, and National University of Singapore faculty members G.V. Shivashankar, J.K.Y. Chan, and C.T. Lim.

Physical markers

MSCs make up only a small percentage of cells in the bone marrow. Other immature cells found there include osteogenic cells, which have already begun the developmental path toward becoming cartilage- or bone-producing cells. Currently, researchers try to isolate MSCs based on protein markers found on the cell surfaces. However, these markers are not specific to MSCs and can also yield other types of immature cells that are more differentiated.

"Conventional cell-surface markers are frequently used to isolate different types of stem cells from the human bone marrow, but they lack sufficient 'resolution' to distinguish between subpopulations of mesenchymal stromal cells with distinct functions," Lee says.

The researchers set out to find biophysical markers for multipotencythe ability to become many different cell types. They first suspected that cell size might be a factor, because fetal bone marrow stem cells, which tend to have a higher percentage of MSCs, are usually small in diameter.

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New technique allows scientists to find rare stem cells within bone marrow

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