How to raise a functional adult Beta-cell: Why stem cell research into a cure for type 1 is not as easy as it seems.
I recently heard someone say “I missed my window! I should have written my parenting book before I had kids! Because back then I thought I knew it all ,but now (as a parent) I know that raising a kid is just too complicated to wrap my head around”. It turns out that something that seems as simple as , have a kid; keep them alive; try not to damage them too much; and they’ll turn out to be functional adults is…. a lot more complicated than that. Any one who’s made it to functional adult status knows that life is full of all these milestones where the right knowledge, resources, people, opportunities and abilities all have to meet in a kind of comic synergy for us to progress and grow into functional adulthood. It turns out that researchers are finding it just as difficult to raise isletcells to functional maturity.
In Type 1 diabetes the function of our isletcells, and specifically insulin producing beta cells is lost, typically to auto immune attack. There are multiple methods currently in research for ways to replace these cells to cure type 1 diabetes. However, the situation is fraught. We don’t have enough donor cells to meet needs, and those that we do have are subject to the same immune attack as the original cells, which requires life-long immunosuppressive therapy. Even then, these cells are shown to only have a limited window of function before the recipient is left honeymooning all over again!
But what if we could grow a cell, from cellular infancy just for that individual? This is what stem cell therapy is all about. Stem cells are basically cells that have not decided what to be when they grow up. So, exposed to the right molecules at the right time and they can grow into anything! Need lung tissue? Stem cells! Need nerve tissue Stem cells! Need Beta cells? Not so fast! There’s a difference between creating a cell, and having it function properly. It’s not enough for an Islet cell to make insulin, it must make the right amount at the right time given the right stimulus. It can’t just reach 6 ft tall and age 18 and call itself a grown up! It has to get a job, do the job and support itself out there as a functional member of our endocrine society.
For this to happen, like a child must be exposed to the right situations, resources, etc, the stem cell must be exposed to the right transcription factors at the right times to mature and function properly. Transcription factors are molecules that cause specific lines of DNA code to be written, copied and read to produce proteins that are then used to build different parts of the cell to provide for different functions. Think of these like people who come into a child’s life and teach them different skills and lessons that will eventually help them in adult life.
These produced beta cells typically mature through the embryonic stages and are still maturing after birth due to, and to meet the needs of, changing nutritional states. .Simulating this process of maturation in a lab has not yet proved possible for humans.
These cells also have to be in the right environment with the right mitochondrial functioning to mature, but how does one achieve the proper environment for maturation without being IN the right environment?! (Hello young adults trying to get a job that requires experience, but they don’t have enough experience to get the job!)
At this time producing a functional mature beta cell by growing a stem cell to maturation has not proven successful in humans, the hope is to be able to directly print (ON a cellular level don’t crack out your inkjet) an already matured cell. This technology is in development and this is one of our most promising prospects for curing existing long-term type 1 autoimmune diabetes.
(By the way, did you know there are about 1,000,000 islet cells in the pancreas, each containing 400-600 beta cells?! That is a LOT of cells to have to raise to maturity!!!! I’m seriously struggling with ONE 4 yr old boy! But I would not trade the dirt and chocolate smudged hugs and kisses of his growing up for anything. *However if someone can start working on the tech to extract some energy from this kid we can solve the world energy crisis tomorrow!*)
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