Perhaps one of the coolest things I have done as a graduate student is work with induced pluripotent stem (iPS) cells. When a cell is pluripotent, it can “differentiate” and become any cell type. With this technology, a patient’s skin cell can be re-programmed and converted into patient-specific heart, liver, nerve, cartilage, and bone cells (to name a few). The introduction of iPS cells to the regenerative medicine community ushered in an era where scientists could generate patient-specific stem cells in the lab, with the hope of developing therapies for various diseases.
Whenever I look into a Petri dish of iPS cells with a microscope, I am constantly inspired by the seemingly limitless research opportunities these cells offer to the biomedical research community.
Unfortunately, the cost of creating patient-specific stem cells is currently astronomical (estimates around $200,000), and preparing the cells for transplantation takes months. Scalability also continues to be an issue for tissue engineers, since a large number of cells are required to produce a functional replacement for failing tissues. However, scientists are pushing the limits of known stem-cell biology to completely bypass the lab and make your body produce the stem cells you need to regenerate your failing tissues, a process known as in vivo reprogramming.
A recent study published in Nature sets the stage for this possibility. Dr. Manuel Serrano and his team at the Spanish National Cancer Research Centre in Madrid have generated a “reprogrammable” mouse line to generate pluripotent cells in live mice. The mice are induced to over-express (or create more of) genes in their cells. This causes the cells to turn into iPS cells. Amazingly, the mice generated iPS cells all over their bodies in various organs. These reprogrammed iPS cells formed tumor-like structures known as teratomas. These teratomas contain tissues, which can continue to develop into any cell type in the body, e.g. nerve, heart, bone, and liver cells.
Unexpectedly, some mice also generated cysts that resembled embryo structures, suggesting the reprogrammed cells have gone beyond the pluripotent state and become “totipotent.” Theoretically, a totipotent cell can generate an entire organism. I still can’t imagine what the scientists thought when they saw embryo-like structures in a mouse they had reprogrammed!
Clearly, the uncontrolled reprogramming of cells in the body is not desired in a clinical setting. However, this paper sets the stage for future studies that will rigorously regulate the reprogramming of cells in a controlled manner to generate specific tissue types, i.e. regenerating heart tissue directly in the body.
The field of regenerative medicine is moving out of the lab and into the body. It is only a matter of time before scientists and clinicians will be able to control the cells in our bodies to stimulate regeneration of failing organs. Images: Wikimedia Commons