At a Glance
- Researchers discovered a self-renewing human skeletal stem cell.
- This study may one day lead to ways to restore bone, cartilage, and supportive tissues for organs.
Stem cells have the potential to develop into some or many different cell types in the body. They can divide throughout life to replenish other cells that become damaged or diseased. When a stem cell divides, each “daughter” cell has the potential to either remain a stem cell or develop into a cell with a more specialized function, such as a bone or cartilage cell.
The most well-studied type of stem cell in bones is called a hematopoietic stem cell, or HSC. These cells give rise to blood cells. Researchers have been looking for the specific stem cells for bone and cartilage. Recent studies in mice identified skeletal stem cells that can give rise to bone, cartilage, and supportive tissue called stromal tissue but not fat, muscle, and other cells.
A team led by Drs. Michael Longaker and Charles Chan of Stanford University investigated whether similar skeletal stem cells exist in humans. They carried out a series of experiments comparing mouse and human skeletal cells and their lineages. The research was supported in part by NIH’s National Institute of Dental and Craniofacial Research (NIDCR), National Heart, Lung, and Blood Institute (NHLBI), and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Results were published in Cell on September 20, 2018.
The researchers first analyzed cells from human tissue that were located in bone growth plate zones, which produce cells for bone growth. Using single cell analysis of RNA sequences, they identified potential human skeletal stem cells with gene expression similar to the previously characterized mouse skeletal stem cells.
The team found and characterized several regions in human bone with distinct cell populations that contained the same cell markers as the mouse skeletal stem cells. These cells could be separated into two categories: unipotent (only able to form one skeletal cell type) and multipotent (able to form many skeletal cell types, including bone, cartilage, and stromal tissue).
By labeling and tracking the cells, the researchers identified the subpopulation of human skeletal stem cells that give rise to bone, cartilage, and stroma. They also created a detailed lineage map of how the stem cells turn into human skeletal tissues. The human skeletal stem cells could be harvested from both fetal and adult bones, as well as derived in the laboratory from induced pluripotent stem cells (which give rise to any cell type). The team also showed that human skeletal stem cells could be generated from specialized cells in fat.
“Every day children and adults need normal bone, cartilage and stromal tissue,” Longaker says. “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.”
—by Tianna Hicklin, PhD
References: Identification of the Human Skeletal Stem Cell. Chan CKF, Gulati GS, Sinha R, Tompkins JV, Lopez M, Carter AC, Ransom RC, Reinisch A, Wearda T, Murphy M, Brewer RE, Koepke LS, Marecic O, Manjunath A, Seo EY, Leavitt T, Lu WJ, Nguyen A, Conley SD, Salhotra A, Ambrosi TH, Borrelli MR, Siebel T, Chan K, Schallmoser K, Seita J, Sahoo D, Goodnough H, Bishop J, Gardner M, Majeti R, Wan DC, Goodman S, Weissman IL, Chang HY, Longaker MT. Cell. 2018 Sep 20;175(1):43-56.e21. doi: 10.1016/j.cell.2018.07.029. PMID: 30241615.
Funding: NIH’s National Institute of Dental and Craniofacial Research (NIDCR), National Heart, Lung and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Cancer Institute (NCI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Human Genome Research Institute (NHGRI), National Institute on Aging (NIA), and National Center for Research Resources (NCRR); California Institute of Regenerative Medicine; Oak Foundation; Hagey Laboratory; Pitch Johnson Fund; the Gunn/Olivier Research Fund; Siebel Fellowship; the Prostate Cancer Foundation; Stanford University; Howard Hughes Medical Institute; Deutsche Forschungsgemeinschaft (German Research Foundation); and Ellenburg Chair.
Originally published in NIH Research Matters on October 2, 2018