It had been two years since his article appeared in Cell, under the characteristically cryptic (to laymen) title: “Mechanosensitive Hair Cell-like Cells from Embryonic and Induced Pluripotent Stem Cells.” As he had explained to the Hearing Restoration audience, his lab works with three kinds of stem cells. The first are embryonic stem cells, which are derived from the inner cell mass of a blastocyst, an early embryo. The lab uses both mouse embryonic stem cells and human embryonic stem cells. (In 2009 President Obama lifted an eight-year ban on federal funding of human embryonic stem cell research, vastly increasing the number of cells available to researchers. The cells are derived primarily from human embryos left after fertility treatments.) Dr. Heller noted that a scientist has to be really “talented” to grow these cells, which involve an underlying structure with other cells on top: if left on their own, they would overgrow everything. “This is quite a bit of maintenance. It’s actually labor-intensive work.”
The second type are the induced pluripotent stem cells (iPSCs) referred to in the title of the 2010 article. These are, according to the NIH website, “adult cells that have been genetically reprogrammed to an embryonic cell-like state.” The NIH definition goes on: “It is not known if iPSCs and embryonic stem cells differ in clinically significant ways.” That Heller and his lab were able to produce sensory hair cells in mice using both these kinds of stem cells is significant. Further, that they were “mechanosensitive” means that they were responsive to mechanical stimulation, and that these responses were similar to those in immature hair cells.
The third type are somatic stem cells, cells isolated from a specific organ—like the human ear. As attractive as these cells are to religious conservatives who oppose embryonic stem cell use, up until now they have not seemed to be a viable option because, as Heller said, “these cells are very rare.”
Embryonic stem cells and pluripotent stem cells share an unfortunate feature: they can generate tumors. Heller said that he’s received many e-mails from patients offering to be subjects for human trials. He showed the audience at the hearing regeneration conference a slide of a mouse that had been injected with a small number of these cells: “After one month, this mouse grows an enormous tumor.” Before they can be used to regenerate hair cells, these stem cells will have to be rendered non-tumorigenic.
Somatic stem cells don’t cause tumors, but there aren’t enough of them. Scientists have not been able to isolate enough of these cells from the ear to study their advantages and disadvantages over the more abundant but problematic embryonic and pluripotent cells. Induced pluripotent stem cells appear to be the perfect compromise. These cells can be generated from virtually any cell of someone’s body, and Heller’s lab has been working with somatic cells derived from skin biopsies, usually from a patient’s arm, a human patient with hearing loss.
“The work is very exciting,” he told me. “Treating the cells from the biopsy with reprogramming factors, they can turn a somatic cell into an induced pluripotent stem cell (iPS cell). They can then grow them in a culture much the way they do embryonic cells, but without the religious or ethical controversy.
“We are basically making hair cells from human skin cells,” he said. “These cells are not from the ear, so making the claim that these are hair cells is a difficult one. But they do have all the features of hair cells. They look like hair cells, they express genes that one would expect to find in hair cells, and they are functional, and moreover, we are approaching the point where we can generate human hair cells.” Many steps remain before this becomes anything like a clinical reality, however, and each step takes a long time and a lot of money.