Rhesus macaques have had bones restored using their own skin stem cells. While we are still a long way from similar treatments in humans, the success of the program marks a big step, or arguably two steps, towards technologies that could transform medicine.
Stem cells are capable of turning into the specialized cells that make up body parts. While embryonic stem cells can turn into any of the body's cells, adult stem cells have a more limited repertoire. However, it is possible to turn adult stem cells from available organs like skin into induced pluripotent stem cells (iPSC) that can produce much needed tissue.
It is hoped that one day iPSCs could provide people with replacement hearts, kidneys or lungs, since if taken from the patient there should be no rejection by the immune system, and ethical debates about the use of embryonic stem cells are avoided. However, until this announcement tests had been restricted to animals relatively distant from humans, such as mice. Worse still, many of the mice developed cancers. Although some progress has been made on reducing oncogenesis, the concerns are obvious.
Dr Cynthia Dunbar of the US National Heart, Lung and Blood Institute says, "We have been able to design an animal model for testing of pluripotent stem cell therapies using the rhesus macaque, a small monkey that is readily available and has been validated as being closely related physiologically to humans.” While the macaque's longer lifespan compared to mice is a disadvantage when it comes to ease of study, Dunbar points out this also makes it a more relevant comparison for humans.
In Cell Reports, Dunbar announced that successful regeneration of bone using skin stem cells. Perhaps more significantly than the fact that bone generation was possible, of the 25 macaques only seven developed tumors known as teratomas. While still an unacceptably high proportion this contrasts with 100% in mice using the same technique. Per cell transferred the monkeys had only one twentieth as many teratomas. The team are investigating methods to reduce the figure further.
The specific project involved reprogramming skin stem cells into bone progenitors and then adding them to ceramic scaffolds used to rebuild broken bones. While this may eventually be applicable to people with drastic bone damage or genetic conditions such as hypochondrogenesis, life threatening conditions are likely to be the first targets for clinical use of iPSC therapy. Consequently, the same team are now working to cause monkey iPSCs transformation into white blood cells and organs such as livers.
"A large animal preclinical model for the development of pluripotent or other high-risk/high-reward generative cell therapies is absolutely required to address issues of tissue integration or homing, risk of tumor formation, and immunogenicity,” Dunbar says.