Researchers at the Stanford University School of Medicine have discovered the stem cell in mice that gives rise to bone, cartilage and a key part of bone marrow called the stroma.

In addition, the researchers have charted the chemical signals that can create skeletal stem cells and steer their development into each of these specific tissues. The discovery sets the stage for a wide range of potential therapies for skeletal disorders such as bone fractures, brittle bones, osteosarcoma or damaged cartilage.

A paper describing the findings will be published Jan. 15 in Cell.

"Millions of times a year, orthopedic surgeons see torn cartilage in a joint and have to take it out because cartilage doesn't heal well, but that lack of cartilage predisposes the patient to arthritis down the road," said Michael Longaker, MD, a professor of plastic and reconstructive surgery at Stanford and a senior author of the paper. "This research raises the possibility that we can create new skeletal stem cells from patients' own tissues and use them to grow new cartilage." Longaker is also co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

An intensive search

The researchers started by focusing on groups of cells that divide rapidly at the ends of mouse bones, and then showed that these collections of cells could form all parts of bone: the bone itself, cartilage and the stroma -- the spongy tissue at the center of bones that helps hematopoietic stem cells turn into blood and immune cells. Through extensive effort, they then identified a single type of cell that could, by itself, form all these elements of the skeleton.

The scientists then went much further, mapping the developmental tree of skeletal stem cells to track exactly how they changed into intermediate progenitor cells and eventually each type of skeletal tissue.

"Mapping the tree led to an in-depth understanding of all the genetic switches that have to be flipped in order to give rise to more specific progenitors and eventually highly specialized cells," said postdoctoral scholar Charles Chan, PhD, who shares lead authorship of the paper with postdoctoral scholar David Lo, MD, graduate student James Chen and research assistant Elly Eun Young Seo. With that information, the researchers were able to find factors that, when provided in the right amount and at the right time, would steer the development of skeletal stem cells into bone, cartilage or stromal cells.

"If this is translated into humans, we then have a way to isolate skeletal stem cells and rescue cartilage from wear and tear or aging, repair bones that have nonhealing fractures and renew the bone marrow niche in those who have had it damaged in one way or another," said Irving Weissman, MD, professor of pathology and of developmental biology, who directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Weissman, the other senior author of the paper, also holds the Virginia and Daniel K. Ludwig Professorship in Clinical Investigation in Cancer Research.

Reprogramming fat cells

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Stanford researchers isolate stem cell that gives rise to bones, cartilage in mice