Stem Cells Made From Skin

Researchers have shown for the first time that it is possible to grow new bone from stem cells made from an animal's own skin cells. While this is not the first successful stem cell therapy tested on animals closely related to humans, it offers another potential source of stem cells for transplantation—the individual’s own adult cells.

In the new study, published online today in Cell Reports, researchers chose a type of monkey called the rhesus macaque as a model for how the technique might work in people. These primates are physiologically similar to humans, especially when it comes to their immune system and how it reacts to foreign bodies.

Researchers harvested skin cells from the monkeys and then genetically reprogrammed them into the equivalent of embryonic stem cells. Unlike adult cells, which are committed to being a specific type of cell (such as skin, bone, or heart-tissue cells), these so-called induced pluripotent stem cells (iPSCs) have the ability to mature into any other type of cell.

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Stem Cells Transformed into Early Bone Cells

Once the researchers had created these changeable cells, the scientists coaxed them into becoming precursors for bone cells. These bone-like cells were transplanted into the monkeys on a ceramic scaffold, which is already used by reconstructive surgeons trying to rebuild human bone.

And it worked. The monkeys implanted with bone stem cells grew new bone on top of the scaffolding. 

Researchers saw no sign of tumor growth when the monkeys were injected with bone precursor cells, a concern raised by earlier experiments in mice. However, a type of tumor called a teratoma did form when researchers injected stem cells that had not yet been transformed into bone precursor cells.

“The teratomas only formed following injection of very high doses of undifferentiated iPSCs into animals,” said Dr. Cynthia Dunbar of the National Heart, Lung, and Blood Institute, in an email to Healthline, “and even then the teratomas grew very slowly and, to our knowledge never spread away from the original injection site in the more than two years that we have followed the monkeys. Teratoma or other tumor formation is a real concern, but our study provides a starting point for investigators and regulators when thinking about how to design human iPSC therapies.”

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Multiple Lines of Stem Cell Research

Before the discovery of how to transform adult cells into iPSCs—a technique pioneered in 2007 by researchers in Japan and Wisconsin—researchers used stem cells obtained from embryos.

Those stem cell lines continue to fuel research into potential therapies for human diseases, and the research is already showing promise. Earlier this year, scientists from the University of Washington transformed embryonic stem cells into heart-muscle cells that were injected into the hearts of monkeys. These cells successfully formed muscle fibers and repaired damaged areas of the heart.

This research, led by Dr. Charles Murry, a University of Washington cardiovascular biology researcher, was two decades in the making. Murry expects the first clinical trials of this stem cell therapy in humans to take place within four years.

While there are risks in any type of stem cell therapy, Murry said his laboratory chose embryonic stem cells because they have a long history of success. These cells also have the advantage of being readily available, making them ideal for treating sudden conditions like damage caused by a heart attack. Currently, it takes time for researchers to generate iPSCs from skin cells, although these types of stem cells can still be useful for chronic conditions like bone degeneration.

Still, Dunbar is convinced that the advantages of iPSCs will make them an important tool in developing new therapies. If stem cells are fashioned from a patient's own cells, that person's immune system is less likely to attack them as foreign invaders. In addition, stem cells created from skin don’t involve the destruction of embryos.

“We believe that iPSCs are likely more advantageous than ESCs (embryonic stem cells) for most clinical applications,” said Dunbar. “First, there are no ethical issues involved in their production. Second and most important, autologous iPSCs can be generated from any individual, and will likely not be rejected by the immune system, in contrast to tissues produced from ESCs.”

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Stem Cell Therapies Could Still Be Years Away

Any new therapy based on stem cells will have to pass through several stages of research, including testing in animals closely related to humans and then clinical trials in people. Depending on the type of therapy and the stem cell source, fully approved treatments could be years away.

While Dunbar has set no timeline yet for the first clinical trials involving iPSCs in people, she and her colleagues plan on expanding their research into other treatment areas.

“Our next step is working on autologous macaque iPSC regeneration models for treatment of liver, heart, and bone-marrow disorders,” said Dunbar. “We hope that the robust model established in this paper can be used to improve the chance that first-in-human iPSC-derived therapies will be safe and effective.”

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