It has been a decade since researchers first discovered the recipe for reprogramming ordinary somatic cells into induced pluripotent stem cells, capable of generating all other cell types in the same way as embryonic stem cells. This was a transformative advance, as the ease of the method allowed near any research group to work with pluripotent cells. Making use of induced pluripotency in research and medicine is still very much a work in progress, however: great strides are being made in the production of cells and tissues for drug testing and other tissue engineering for research use, but the goals of generating patient-matched cells and tissues for cell therapies and transplantation are not proceeding as smoothly as was perhaps hoped by some. This popular science article surveys the field:
Human cortex grown in a petri dish. Eye diseases treated with retinal cells derived from a patient's own skin cells. New drugs tested on human cells instead of animal models. Research and emerging treatments with stem cells today can be traced to a startling discovery 10 years ago when researchers reported a way to reprogram adult mouse cells and coax them back to their embryonic state - pluripotent stem cells. A year later, they accomplished the feat with human cells. The breakthrough provides a limitless supply of induced pluripotent stem cells (iPSCs) that can then be directed down any developmental path to generate specific types of adult cells, from skin to heart to neuron, for use in basic research, drug discovery and treating disease. The dazzling iPSC breakthrough has spurred rapid progress in some areas and posed major challenges in others. It has already proved a boon to basic research, but applying the new technology to treat diseases remains daunting. Some types of cells have proved difficult to reprogram, and even the protocols for doing so are still in flux as this is still a very young field.
Six years after the iPSCs discovery, researchers in a very different field developed a new gene-editing technology of unprecedented speed and precision, known as CRISPR-Cas9. The potent new tool has revolutionized efforts to "cut and paste" genes and has been very quickly adopted by thousands of researchers in basic biology and drug development. CRISPR's speed and precision may some day allow stem cell researchers to reach their most ambitious goal: Genetically abnormal cells from patients with inherited diseases such as sickle cell anemia or Huntington's could be reprogrammed to the pluripotent stem cell state; their genetic defects could be "edited" in a petri dish before being differentiated into healthy adult cells. These cells could then be transplanted into patients to restore normal function. While that goal is still beyond reach, many early-stage clinical trials are underway using induced iPSCs to treat diseases, from diabetes and heart disease to Parkinson's. One trial has already treated its first patient. In 2014, scientists made iPSCs from skin cells of a woman with macular degeneration and then differentiated them into adult retinal cells. Surgeons transplanted the retinal cells into her eyes in order to treat the disease - the first patient treated using iPSCs. Preparations to treat a second patient using patient-derived cells were stopped because the researchers detected a mutation in one of the genes in the iPS cells. No reports had linked the gene to cancer, but they decided not to use the stem cells to eliminate any risk.
The success of treatments relies in part on stem cells' rapid rate of proliferation. Hundreds of billions of cells may sometimes be needed for a transplantation. But if just a few of the stem cells fail to differentiate into the target adult cells, they may reproduce rampantly when transplanted and form a tumor. "It's a two-edged sword. In the pre-transplant stage, you want stem cells that proliferate very rapidly. But after the transplant, if there are only five or 10 cells that didn't differentiate into adult cells, they can reproduce infinitely. They create a kind of residue of tumor." Research to ensure that all stem cells differentiate before transplantation is now one of the main issues in this field. To eliminate cancer risk, the researchers are now "deep sequencing" the genetic makeup of each of the stem cell lines they might use. They have also decided to use donor cell lines rather than the patient's own cells. This avoids the very expensive prospect of having to carry out quality checks like deep sequencing of each patient's own pluripotent cell lines.
The originators of the iPSC methodology are concerned about public perception that the rate of progress may be slower than expected. "I am fascinated by how rapidly science is advancing. It's amazing. But for the most part, developing new treatments - doing the science, testing the safety and effectiveness of new therapies - takes a great deal of money and many years. Developing new treatments may take 10 years, 20 years, 30 years. That is what we have been trying to say to our patients: 'We are making great progress, so do keep up your hope. But it takes time.'"