Revolutions: The incredible potential of induced pluripotent stem cells
Revolutions is a series that brings together a hand-picked selection of recent articles canvassing cutting-edge insights into major scientific advances. This installment brings you up to date with the ground-breaking new discoveries made around the regenerative possibilities of induced pluripotent stem cells, which can theoretically be coaxed into any kind of cell in the human body.
The story of how Japanese researchers discovered induced-pluripotent stem cells (iPSCs) in 2006 is a fascinating one, and one that has presented medical researchers with a whole new world of opportunity. The Nobel Prize-winning technology emerged from the lab of researcher Shinya Yamanaka at Kyoto University, who through five years of tinkering finally brought the embyronic-like stem cells to life in tiny, microscopic clusters. Even he was surprised to see it with his own eyes.
Two weeks before that, these induced pluripotent stem cells, as they came to be known, were simply regular skin cells from adult mice. By harvesting them and infecting them with a virus intended to introduce 24 carefully selected genes, Yamanaka and his team were able to effectively turn back time, returning these cells to their early, developmental stage with a renewed ability to diversify into skin cells, nerve cells or pretty much any other cell type in the human body.
"At that moment, I thought, 'This must be some kind of mistake'," Yamanaka said, according to an account of the discovery in Nature.
But repeat experiments proved it to be anything but and the breakthrough would serve as a springboard for all kinds of medical research pursuits. Suddenly the thick, morality-lined clouds that hovered over embryonic stem cell research were parting to make way brighter, happier times. And stem cells harvested from adult cells rather than embryos would not only be a lot less controversial, but promise some practical benefits too, including lower risks of rejection by the immune system because they can be created from a patients own cells.
Thirteen years on, Yamanaka has earned a Nobel Prize in Physiology or Medicine for his discovery (jointly award to him and Sir John B. Gurdon in 2012), and scientists have built on his work and tweaked his recipes to bring about some truly exciting advances. While iPSCs are a versatile scientific tool that are also proving useful in modeling disease and screening drugs, here we focus on their huge promise in the field of regenerative medicine.
Rebuilding the eyeball?
The eyeball is a very complex organ with delicately layered bits and pieces, such as the lens, cornea and conjunctiva, the mucous membrane that shields the front of the eye. A joint research effort from Osaka and Cardiff University's in 2016 explored how iPSCs might be able to put these together piece by piece as a way of restoring vision in humans.
The researchers were able to use the stem cells to generate multiple cell lineages of the aforementioned pieces of the puzzle. This resulted in tissues that were then implanted into the eyes of rabbits with induced corneal blindness, to repair the organ and restore their vision. The researches say this work could pave the way for trials that explore the technology's potential in humans.
"This research shows that various types of human stem cells are able to take on the characteristics of the cornea, lens and retina," Professor Andrew Quantock, co-author of the study, said at the time. Read more.
Taking the fight to Parkinson's
As Parkinson's disease takes hold in the human brain, it causes a decline in dopamine production which in turns hampers a sufferer's motor skills. But could iPSCs be brought in to arrest the slide? Research from Kyoto University published in 2017 explored this possibility in diseased monkey brains by converting the cells into dopaminergic progenitors, which are neurons responsible for generating the dopamine neurotransmitter.
And things went well. So well, in fact, that those same researchers are now charging ahead with human trials using the same technology. This saw seven Parkinson's patients each have five million iPSC-derived dopaminergic progenitors transplanted into their brains with a specialized device. The hope is that these will become dopaminergic neurons and curtail the effects of the disease. The trials kicked off last August with the patients to be closely observed for two years thereafter. Read more.
Putting a spinal cord back together again?
With its many moving parts, the spinal cord is notoriously difficult to repair once its becomes injured, but could iPSCs be the glue that holds it together once again? Research published last year from the University of Minnesota describes a cutting edge technology whereby the cells can be converted in neuronal stem cells. These can then be mixed and matched with alternating layers of silicon scaffold (seen above) and used to grow new connections in the spine between the nerves that remain.
The researchers put this new device to the test in the lab and found that it was able to grow new nerves and connect undamaged, but separated cells. While these experiments showed that the technology could grow new neurons in an injury site, doing so in numbers that would allow a paralyzed patient to walk again is a long ways off. In saying that, even a partial repairing of the spinal cord can improve functions like bladder control and avoid involuntary movements of the limbs, so there are plenty of reasons to be excited.
"These simple improvements in function could greatly improve their lives," Ann Parr, co-author of the study, said at the time. Read more.
Giving diabetics their insulin production back
A lot of recent research is tracing the inability of diabetics to properly produce insulin back to faulty beta cells in the pancreas, so plenty of scientists are looking at ways to restore their function. Researchers at Washington University in St. Louis made an exciting breakthrough in this area in January, publishing a paper describing a new method of converting iPSCs into much-needed beta cells.
The team tested their new beta cells by implanting them into diabetic mice incapable of producing insulin on their own. Within days, the mice began secreting insulin, and did so enough quantities to control their own blood sugar levels and functionally cure their diabetes. The researchers are now thinking up ways to safely test the technology in humans. Read more.
Regrowing damaged hearts
Last year, the Japanese government approved a first-of-a-kind trial on humans, where iPSCs are used to create sheets bearing millions of heart muscle cells and then grafted onto the hearts of patients with heart disease.
This followed successful trials on pigs the year before, and it is hoped that with the help of growth factors, the sheets will promote the regeneration of damaged muscles and improve the function of the organ. This initial trial involved three patients, but the team has hopes for larger trials involving 10 patients if everything goes to plan, and commercial availability of the technique thereafter. Read more.
There's no shortage of researchers vying for breakthroughs in the realm of male pattern baldness, and lately we're seeing how stem cells might play a big role in the big hair revival. Way back in 2014 we looked at a breakthrough where scientists had converted iPSCs into epithelial stem cells, stem cells hat are normally found at the bulge of hair follicles, which then gave rise to hair follicles on the skin of immunodeficient mice.
Other research published in 2015 described a technique whereby iPSCs could be coaxed into the form of dermal papilla cells, which regulate the formation of hair follicles, and were transplanted into mice to trigger new hair growth. And in 2017, a paper by researchers from the University of Southern California described a process where skin cells were harvested from adults and the molecular events behind their growth was examined and replicated in iPSCs to grow new hair follicles in mice.
As we can see, iPSCs are already opening up an incredibly diverse array of medical possibilities, and at just 13 years young, this is likely just the tip of the iceberg.
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But opponents screamed and hollered and flat out lied that there was a *total ban* on fetal stem cell research.
Biologists seeking to avoid the whole kerfluffle, but still desiring to use taxpayer funding instead of private money, turned to figuring out how to find stem cells and make alterations to cells obtained from humans able to give their consent to sample taking. That's led to these discoveries and inventions for making one type of cell change into a different type, rather than using fetal cells that are initially totipotent and attempting to control what they become.
This field of science has become a lot better since it was for a time cut off from what people assumed was the best path, and better for having part of its government funding taken away.
As for fixing damaged spinal cords, what's been going on with using allografts of olfactory nerve ensheathing cells? It's had great results in various animal tests but AFAIK only one human has had the treatment - 7 years after his spinal cord was completely severed when he was stabbed in the back. Last I know of the guy is he was getting around with a walker, and that was a few years ago. How's he doing today?
Looks to me as though all these other things people are dinking around with for spinal cord repair are in part being worked on as ways to make more money or make spinal cord repair a much longer process or maintain it as a chronic condition requiring life-long treatment VS a 'one and done' treatment that cures without doing anything more than physical rehabilitation.
I was offered the opportunity to participate in a trial of stem cell therapy at one of Australia's prestigious hospital/research centers . In a nut shell the trial involved inflaming the ischaemic heart muscle via maximal stress testing (stationary bicycle) and then having several days of Colony Stimulating Factor G-CSF via subcutaneous injections.
G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
The putative mechanism was thought to be that the inflamed heart muscles signaled the stem cells and they then migrated and "turned" into muscle and perhaps arterial cells.
Over the next ten years I made a remarkable recovery. I can now do most tasks including gardening, lawn mowing, building renovations, lift sleepers, bags of concrete etc. I can now walk up hills and swim a kilometer etc.
Some of the other effects seem to indicate that the changes made by the stem cells are ongoing and I have returned to having a muscular physique with 6mm skin fold thickness and a 56 kg right hand grip strength, and I am able to complete 10 chair stands in 10 seconds.
A friend had similar results.....