What are stem cells?

What if adult stem cells were lengthened temporarily via telomerase, audited for mutations using host DNA as a template, then grown into a fully functioning organ, rechecked for mutations, and then transplanted into the host's body?

• Would you have a "younger" organ that is specific to the individual, therefore no possibility of rejection from the host body? I am thinking of people with progeria and folks with organ failure. I realize much of this is not within our capability yet. However, if we did have the ability to carry out this procedure, would it work? Or is there some other factor that I'm not considering? I recognize that telomerase is heavily involved in cancer research and the stem cells would likely become cancerous if its telomerase activity was left functioning. I'm thinking that we could use telomerase to lengthen telomeres to a healthy level, and then shut off the telomerase after we have achieved the desired results. After, check for mutations by sequencing the genomes of the stem cells and the host DNA and comparing with computers. Program the stem cells into a specific organ, like a human heart. Check once for functionality and a second time for mutations. Finally, transplant organ into the host body.

• Answer:

  Regnerative medicine using a patient's own stem cells is both a hot research topic and something that we'll eventually be able to do, possibly within our lifetimes. However, using adult stem cells isn't the way it will be done. There are two broad classes of potency -- the number of different tissue types that a cell can naturally become -- regarding stem cells. To be able to grow organs in vitro, you'd need pluripotent stem cells [1: I'm simplifying a bit; follow the footnote if you care.], which are capable of differentiating into all of the tissues in the body. The only cells in the history of any individual human being that have this property are the embryonic stem cells present for only a few days during embryogenesis. Adults still have stem cells, but they're merely multipotent -- meaning that they're capable of differentiating into only a limited number of tissue types. As a result, there are no native cells in an adult human that would be suitable for this type of regenerative medicine. However, relatively recent work by Shinya Yamanaka's group (for which he shared a Nobel prize) demonstrated that we can treat somatic cells with four transcription factors and convert them into pluriopotent embryonic stem-cell like cells called induced pluripotent stem cells (iPS cells). These cells are capable of differentiating into lots of different cell types, but we're currently working on understanding how to go from cells to tissues to functioning organs. Organogenesis is an incredibly complicated process, and trying to simulate it in the lab will be quite difficult. We have the raw materials, but we don't quite know how to transform them into finished organs. Using iPS cells -- which essentially carry out the transcriptional program of embryonic stem cells -- circumvents a lot of the issues associated with attempting to tune telomere lengths. Through billions of years of evolution, embryonic stem cells have already arrived at the optimal solution for regulating telomerase activity, sparing us the effort of figuring out how to get it just right. Checking for and repairing muations is feasible but currently laborious -- getting the genome sequence of a colony of iPS cells is trivial, and repairing damage with a system like Cas9 can be done, but it's going to take a while. [1] The class of stem cells that can make everything are totipotent cells -- in contrast to pluripotent cells (which can make all of the tissues in the body), totipotent cells can also make all of the extraembryonic tissues (like the placenta) required for embryonic implantation and growth. Since these are tissues that are only relevant in the context of pregnancy, totipotency isn't strictly required.