A decade-long effort led by Stanford University School of Medicine scientists has been rewarded with the identification of the human skeletal stem cell.

The cell, which can be isolated from human bone or generated from specialized cells in fat, gives rise to progenitor cells that can make new bone, the spongy stroma of the bone’s interior and the cartilage that helps our knees and other joints function smoothly and painlessly.

The discovery allowed the researchers to create a kind of family tree of stem cells important to the development and maintenance of the human skeleton. It could also pave the way for treatments that regenerate bone and cartilage in people.

“Every day, children and adults need normal bone, cartilage and stromal tissue,” said Michael Longaker, MD, professor of plastic and reconstructive surgery. “There are 75 million Americans with arthritis, for example. Imagine if we could turn readily available fat cells from liposuction into stem cells that could be injected into their joints to make new cartilage, or if we could stimulate the formation of new bone to repair fractures in older people.”

A paper describing the finding was published online Sept. 20 in Cell.

Longaker, the Deane P. and Louise Mitchell Professor in the School of Medicine and the co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, is the senior author. The lead authors are Charles K.F. Chan, PhD, assistant professor of surgery; medical student Gunsagar Gulati, MD; Rahul Sinha, PhD, instructor of stem cell biology and regenerative medicine; and research assistant Justin Vincent Tompkins.

‘True, multipotential, self-renewing’

The skeletal stem cells are distinct from another cell type called the mesenchymal stem cell, which can generate skeletal tissues, fat and muscle. Mesenchymal stem cells, which can be isolated from blood, bone marrow or fat, are considered by some clinicians to function as all-purpose stem cells. They have been tested, with limited success, in clinical trials and as unproven experimental treatments for their ability to regenerate a variety of tissues. Recently, three elderly patients in Florida were blinded or lost most of their sight after mesenchymal stem cells from fat were injected into their eyes as an experimental treatment for macular degeneration.

“Mesenchymal stem cells are loosely characterized and likely to include many populations of cells, each of which may respond differently and unpredictably to differentiation signals,” Chan said. “In contrast, the skeletal stem cell we’ve identified possesses all of the hallmark qualities of true, multipotential, self-renewing, tissue-specific stem cells. They are restricted in terms of their fate potential to just skeletal tissues, which is likely to make them much more clinically useful.”

Skeletal regeneration is an important capability for any bony animal evolving in a rough-and-tumble world where only the most fit, or the fastest-healing, are likely to survive very long into adulthood. Some vertebrates, such as newts, are able to regenerate entire limbs if necessary, but the healing ability of other animals, such as mice and humans, is more modest. Although humans can usually heal a bone fracture fairly well, they begin to lose some of that ability with age. And they are completely unable to regenerate the cartilage that wears away with age or repetitive use. Researchers have wondered whether the skeletal stem cell could be used clinically to help replace damaged or missing bone or cartilage, but it’s been very difficult to identify.

Adult stem cells lineage-restricted

Unlike embryonic stem cells, which are present only in the earliest stages of development, adult stem cells are thought to be found in all major tissue types, where they bide their time until needed to repair damage or trauma. Each adult stem cell is lineage-restricted — that is, it makes progenitor cells that give rise only to the types of cells that naturally occur in that tissue. For our skeleton, that means cells that make bone, cartilage and stroma.