Humans near regrowing limbs
*Gene therapy raises hope of paralysed people moving again
The dream of regrowing human body parts could become a reality after a major scientific breakthrough.A stem cell has been identified which causes a humble flatworm to regrow a head, brain or other tissue – a breakthrough that has huge potential for people.
Regenerative medicine, where skin cells or even entire organs are regrown, could one day provide a cure for a number of conditions.These range from birth defects and blindness to diabetes, heart disease and cancer.A team of experts from the Stowers Institute for Medical Research in Kansas City, Missouri, found the cell – which can regenerate an entire organism – after pioneering a technique using flow cytometry that scans cells in fast moving blood.
They isolated the amazing cell in the planarian flatworm before it performed its remarkable regenerative act.Some scientists believe the worm, that lives in ponds and lakes, holds the key to immortality.The cell, which has been named Nb2, is a form of adult pluripotent stem cell – unspecialised ‘master’ cells found in humans that develop into many types of tissue and organs.
The full findings were published in the journal Cell.Also, scientists believe gene therapy could help hundreds of thousands of paralysed patients regain control of their arms and legs again.Researchers gave the treatment to paralysed rats – and found it allowed them to pick up sugar cubes using their paws.
The breakthrough study, by a team of neurosurgeons at King’s College London, has been branded ‘exciting’ and ‘life-changing’.Charities told the BBC that it is some of the most ‘compelling’ evidence that people left paralysed can regain the use of their arms and hands.Patients with spinal cord injuries often lose their ability to perform everyday actions that require coordinated hand movements, such as holding a toothbrush.Regaining hand function is the top priority for patients and charities claim it would dramatically improve independence and quality of life.
After a traumatic spinal injury, dense scar tissue forms which then prevents new connections being made between nerve cells.No regenerative treatments are currently available – but the new study offers hope of a potential way of helping patients regain function.How was the study carried out? Rats and humans use a similar sequence of coordinated movements when reaching and grasping for objects.
What did they find? Researchers found that after two months, the rats given gene therapy were able to reach and grasp sugar pellets with their paws.They also discovered a ‘dramatic’ increase in activity in the spinal cord of rats, which suggested new connections had been made by nerve cells.Professor Joost Verhaagen, of the Netherlands Institute for Neuroscience, who was part of the study, praised the findings.He said: “The use of a stealth gene switch provides an important safeguard and is an encouraging step toward an effective gene therapy for spinal cord injury.
“This is the first time a gene therapy with a stealth on/off switch has been shown to work in animals.”However, the KCL researchers warned the gene therapy is not yet ready for humans because of an error in the treatment.The study showed a small part of the gene remained active – even when the therapy was switched off. They hope to switch it off.
Senior author, Prof. Alejandro Sanchez Alvarado, a molecular biologist at the Howard Hughes Medical Institute and investigator at the Stowers Institute for Medical Research, Kansas City, said: “This is the first time an adult pluripotent stem cell has been isolated prospectively.
“Our finding essentially says this is no longer an abstraction, that there truly is a cellular entity that can restore regenerative capacities to animals that have lost it and that such entity can now be purified alive and studied in detail.”
What is more, it was pinpointed thanks to a ‘marker’, or biological sign, that is also present in humans – a protein known as piwi-1.Professor Sanchez Alvarado added: “The fact the marker we discovered is expressed not only in planarians but also in humans suggests there are some conserved mechanisms that we can exploit.
“I expect those first principles will be broadly applicable to any organism that ever relied on stem cells to become what they are today. And that essentially is everybody.”What causes species to regenerate? All organisms, including humans, have the ability to regenerate to a degree, but the process is much more developed in many invertebrates such as earthworms and starfish.
These animals can grow new heads, tails and other body parts when injured.Scientists don’t know why mammals don’t have the same ability, but they do regenerate skin, muscle and blood.Every multicellular organism is built from a single cell, which divides into two identical cells, then four, and so on.
Each of these cells contains the exact same twisted strands of DNA, and is considered pluripotent – meaning it can give rise to all possible cell types in the body.But somewhere along the way, those starter cells – known as embryonic stem cells – resign themselves to a different fate and become skin cells, heart cells, muscle cells, or another cell type.
In humans, no known pluripotent stem cells remain after birth. In planarians, they stick around into adulthood, where they become known as adult pluripotent stem cells or neoblasts. Scientists believe these neoblasts hold the secret to regeneration.Neoblasts have been studied since the late 1800s. But only in the last couple of decades have advanced experimental and molecular techniques discovered there are many varieties, all with different properties and patterns of gene expression. Professor Sanchez Alvarado explained: “We might have to transplant over a hundred individual cells into as many worms to find one that is truly pluripotent and can regenerate the organism.
“That is a lot of work, just to find the one cell that fits the functional definition of a true neoblast.“And if we want to define it molecularly by identifying the genes that cell is expressing, we have to destroy the cell for processing. There was no way to do that and keep the cell alive to track it during regeneration.”One feature that had long been used to distinguish neoblasts from other cells is piwi-1, so co author Dr An Zeng separated those that expressed this from those that did not. Only those that were high in the protein qualified as neoblasts.
Prof Sanchez Alvarado said: “This kind of simultaneous quantitative analysis of gene expression and protein levels had never been done before in planarians.“We could not have done it without the amazing scientific support facilities here at Stowers, including molecular biology, flow cytometry, bioinformatics, and imaging groups.
“Many researchers had assumed that all cells expressing piwi-1 were true neoblasts, and it didn’t matter how much of the marker they expressed. We showed it did matter.”
Through a process of elimination involving about 8,000 cells rich in piwi-1 – which managed to rule out those destined for a particular fate like muscle or skin – Dr Zeng was left with two types that could still be pluripotent, which he named Nb1 and Nb2.The Nb2 subgroup expressed tetraspanin, a group of evolutionarily ancient and poorly understood proteins that sit on the surface of cells.What are stem cells? Stem cells are a basic type of cell that can change into another type of more specialized cell through a process known as differentiation.Think of stem cells as a fresh ball of clay that can be shaped and morphed into any cell in the body.
They grow in embryos as embryonic stem cells, used to help the rapidly growing baby form the millions of different cell types it needs to grow before birth.In adults they are used as repair cells, used to replace those we lose through damage or ageing.Stem cells have been the focus of lots of medical research in recent decades because they can be used to grow almost any type of cell.
So Dr Zeng made an antibody that could latch onto it, pulling the cells that carried it out of a mixture of other suspected neoblasts. He then transplanted the single purified cell into a planarian that had been subjected to lethal levels of radiation.Not only did these cells repopulate and rescue the irradiated animals, but they did so 14 times more consistently than cells purified by older methods.Prof Sanchez Alvarado said: “We have enriched for a pluripotent stem cell population, which opens the door to a number of experiments that were not possible before.”
Previous research by the University of Nottingham has suggested flatworms could live forever after examining their ability to repeatedly regenerate.Six years ago experts created a colony of more than 20,000 flatworms by chopping one into pieces and observing each section grow into a new complete worm.They believe it could help scientists develop new methods to allow humans to stay younger for longer.Zoologist Professor Aziz Aboobaker said at the time: “Our data satisfy one of the predictions about what it would take for an animal to be potentially immortal.”
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