Stanford Researchers Identify Human Bone Stem Cells

In a study published on September 20, 2018, a team of researchers at the Stanford University of Medicine identified a multipotent human skeletal stem cell that gives rise to new bone or cartilage in the body. The implications of this study can lead to new regenerative treatments for fractures, arthritis, and bone injuries.

Stem cells are cells that have not yet been differentiated and can self-renew for extremely long periods of time to keep their colonies intact. Once differentiated, stem cells become specialized cells required for regenerative therapy. These cells then differentiate into specialized cells called progenitor cells, which make up human tissues. The adult stem cell is lineage-restricted, meaning that it can give rise only to certain types of tissue like bone, cartilage, and stroma.

The cell can also be isolated from human bone and even be generated from specialized cells in fat. They can also arise from induced pluripotent stem cells (iPSCs), a hot-topic technology in current stem cell research. The stem cell is found in increased quantities at the end of a developing bone or the site of a healing fracture.

These stem cells are different from mesenchymal stem cells, which have had limited success in various clinical trials. Mesenchymal stem cells are isolated from the blood, bone marrow, and fat, and are considered to be all-purpose stem cells. However, these stem cells are very loosely characterized and may actually comprise of a large variety of cell populations, which may account for why they respond differently and unpredictably to differentiation signals.

“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,” said Charles K.F. Chan, PhD, assistant professor of surgery at Stanford.

This study is a large advancement for stem cell research partly because it does not include ethical complications that are otherwise attached to the field of stem cell research. Pluripotent stem cells are usually derived from embryonic stem cells, which come from human embryos and exist only at early developmental stages. This stem cell, in contrast, bides its time in adult tissue until it differentiates.

“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,” said Michael Longaker, MD, professor of plastic and reconstructive surgery at Stanford.

Another implication of the study is that it provides a technological advantage convenient for researchers working with human hematopoietic stem cells–that is, the stem cells in human bone marrow that give rise to the blood and immune system. These skeletal stem cells don’t require growth factors in the serum used as the environment containing hematopoietic stem cells. Instead, they provide an environment where hematopoietic stem cells can thrive. The stromal population that arises from the skeletal cell can keep hematopoietic stem cells alive for two weeks without the need for additional serum.

Researchers of the study also constructed a family tree of stem cells, which could be used in clinical applications and provide a way to understand the similarities and differences between mouse and human skeletal stem cells. This, in turn, may lead to discovery of key evolutionary differences between humans and mice. The researchers had used the mouse skeletal stem cell to locate and isolate the human skeletal stem cell by comparing gene expression profiles of the mouse skeletal stem cell with those of cell populations at the end of bones.

“I would hope that, within the next decade or so, this cell source will be a game-changer in the field of arthroscopic and regenerative medicine,” Longaker noted. “If we can use this stem cell for relatively noninvasive therapies, it could be a dream come true.”