Mel Brooks’ movie, Young Frankenstein, opens with Dr. Frankenstein giving a lecture to a group of medical students. In one interaction about the reanimation of life, a student mentions that scientists have been able to do remarkable things with hearts and kidneys. Dr. Frankenstein responds that “Hearts and kidneys are tinker toys. I am talking about the central nervous system!” Dr. Frankenstein’s propensity for exaggeration aside, over the last fifty years we have been able to do remarkable things with organ donation. Two new studies using animal models provide a proof-of-concept for using organs from non-human sources or growing new organs in the lab.

The biggest problem with organ donation is that more people need organs than are available. Unlike other instances of limited medical supplies, at least for now, this one cannot be mitigated with more money or more efficient manufacturing processes. Scientists have explored obtaining organs from non-human sources, or manufacturing organs using stem cells as potential solutions to this problem. Both have encountered formidable hurdles.

The first option is to obtain organs from non-human sources such as baboons. This is known as xenotransplantation. However, the body is very good at recognizing foreign material. This is usually a good thing for fighting off disease and infection, but in the case of organ donation, it is problematic. Typically, a patient must take immunosuppressant drugs even when the donor is a match because the body will reject the organ. This problem is only worsened in cases of interspecies transplantation.

New research shows promise of eventually overcoming this hurdle. Scientists from the National Heart, Lung, and Blood Institute and the National Institutes of Health have successfully implanted a pig’s heart into a baboon that remained healthy for one year after the transplant. They accomplished this using a combination of genetic engineering and directed immunotherapy. They created a genetically engineered pig with the genes that cause rejection in humans removed and the genes that promote compatibility inserted. They then used new immunosuppressant techniques that involve targeting specific areas rather than the entire immune system.

This research is still in its early stages, though. The pig’s heart did not replace the baboon’s heart, but was only incorporated into the circulatory system and resided in the abdomen. The experiment shows that the baboon’s immune system did not reject the heart. Now, the next step will be to replace the baboon’s heart with the genetically engineered pig’s heart to see if it functions properly.

Xenotransplantation is one solution to the limited supply of organs. A second potential solution is manufacturing organs using stem cell techniques. The only organs that have been successfully grown in the lab and transplanted to a patient are hollow organs, such as the trachea or bladder. Even in these cases where the patient’s stem cells are used to grow the organ onto a scaffold, there have been difficulties in integrating the organ into the body. Solid organs, like kidneys or hearts, can only be grown on a very small scale because there is no way to get oxygen and nutrients within the organ.

One solution may be to determine the correct genetic “switch” to turn on or off in cells to grow a particular organ, insert those cells into the body, and grow the organ in vivo. Scientists from the University of Edinburgh used connective tissue cells from a mouse embryo (these are different cells from embryonic stem cells) and converted them into thymic epithelial cells using a genetic switch called FOXN1. These thymic epithelial cells were mixed with other thymus cells and grafted onto the kidney of a mouse. The cells grew into a complete and fully functioning thymus, an important organ in the immune system.

Like the experiment with the pig’s heart grafted into the baboon, this experiment is in its early stages, and will not be ready for humans any time soon. However, these advances provide a proof-of-concept for two potential solutions to a shortage of needed organs. Whether we can go so far as to call hearts and kidneys “tinker toys,” we have certainly come a long way in manipulating organs in the lab.

Article references:

“An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts” by Nicholas Bredenkamp, et al. Nature Cell Biology, 2014 (by subscription only).

“Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation” by Muhummad M. Mohiuddin, et al. The Journal of Thoracic and Cardiovascular Surgery, 148 (3), 2014 (by subscription only).