It's a glorious day for regenerative medicine today. Researchers at the Howard Hughes Medical Institute (Harvard) reported in Nature that they have managed to convert adult enzyme-producing pancreatic cells into insulin-producing beta cells in living mice.
Here's the direct abstract:
One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
It's an amazing and important breakthrough because the prevalent idea in medical research is that:
a) Cells go from an undifferentiated embryonic state to a highly differentiated specialized state.
b) Once the cells commit to a specialized state, they cannot de-differentiate or revert back into an embryonic state anymore.
c) Highly specialized cells are thus imprisoned in their narrow specialized roles and cannot convert into other specialized cells
This was the basic reason why we thought that we needed exclusively stem cells or embryonic cells from fetuses to carry out research into generating specialized cells of our choice. We believed that only embryonic cells had the potency to transform into other cells. The Harvard scientists converted a regular pancreatic exocrine cell that usually secretes digestive pancreatic enzymes to an endocrine pancreatic cell that secretes insulin! This topples the whole belief-cart that only embryonic cells can do this.
I think regenerative research officially enters a new era with this cool little cellular role-reversal trick. How these scientists did it is even more fascinating. A mere THREE regulatory genes were transported into the pancreas using small vector viruses. These viruses preferentially infected the EXOCRINE cells of the pancreas and not the endocrine cells (that are found inside "islets" of the pancreas). Within ONE MONTH, the infected exocrine cells transformed into the endocrine insulin-secreting cells and they have continued to be endocrine insulin secreting cells for a complete NINE MONTHS now!
You can see the transformation in the photograph of the pancreatic tissue slice above. The red round spot is one islet (of langerhans) in the pancreas. This contains the endocrine insulin secreting cells. Within a month the same area changes to show that insulin-secreting cells have sprung up OUTSIDE the islet! One adult cell turns into another totally different adult cell!
As a simplified analogy, what they have managed to do is the cellular equivalent of turning a car (exocrine pancreatic cell) into a space-shuttle (endocrine islet cells) by just sending in three astronauts (vector-viruses) into the car to pull three levers (genes).
A couple years back, some Japanese scientists converted adult mice skin cells into stem cells but to reconvert them back into some other adult cell would have required a lot more manipulation. Considering the analogy above, it would be like converting the car into scrap metal first and then thinking about how to convert the scrap metal into the space shuttle. Do-able but yet, a step too many. This past experiment by the Japanese generated keys ideas for the Harvard group:
a) Relatively small number of genes could do the trick.
b) If the parent cell and the target cell shared a lot of common genes then maybe, just maybe the parent cell would directly convert into the target cell (and it did!).
They carefully sorted and drilled down through more than a thousand genes to finally arrive at three (Ngn3, Pdx1, and Mafa) transcription associated genes to do the transforming job.
And remember all this was done in LIVE MICE! So what happened to the mice? Some of these mice were diabetic and the additional surge of insulin from the converted cells *reduced the blood glucose levels* in these mice! Even better news was that the converted cells have stuck around for NINE months now. Nine months of blood-glucose control WITHOUT insulin injections or any other medication.
Though this research was carried out in mice, it is quite possible that it might be possible in humans as well. Some problems that the researchers are careful to point out are:
--> A vector virus was used to carry the genes inside the pancreas. What could we possibly use in humans? We cannot use a vector virus because its a LIVING organism that can potentially transform into something else infectious! The risk is just not worth it.
--> Can we use other unrelated cells to the same effect? In other words, if we need to build, say, a heart, would we need heart cells to start with or could we do with skin cells? Could these insulin-secreting cells have been generated from some other cells - other than closely related exocrine-enzyme-secreting pancreatic cells?
Till these questions are answered, we will need stem cells, embryonic cells and research using these cells (BACK OFF. GEORGE IDIOT BUSH!). We cannot just toss them in the trash. This new approach of converting one adult cell to another is very much an unknown angel. But what an awesome angel!! Their potential is mind-boggling!
