The dream of regenerating human body parts could become a reality after a major scientific advance.
A stem cell has been identified through which the humble worm regrows a head, brain or other tissue – a breakthrough that has huge potential for people.
From replacement skin to entire organs, it is hoped regenerative medicine will one one day provide a cure for conditions ranging from birth defects and blindness to diabetes, heart disease and cancer.
Now a US team has found the one cell that can regenerate an entire organism after pioneering a technique using flow cytometry that scans cells in fast moving blood.
By combining it with genomics, single cell analysis and other imaging 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 actually a form of adult pluripotent stem cell – unspecialised ‘master’ cells found in humans that develop into many types of tissue and organs.
Senior author Professor Alejandro Sanchez Alvarado, a molecular biologist at the Howard Hughes Medical Institute at 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.
Added Prof Sanchez Alvarado: “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.”
All organisms, including humans, have the ability to regenerate something. 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.
The researchers say the study published in Cell may lead to a way of growing replacement organs and limbs in humans that have less regenerative capacity.
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.
Prof 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.
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 Prof 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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