408-854-1883 starts at $30 per hr home care

Affordable in home care | starts at $28 per hr

Algae to crude oil: Million-year natural process takes minutes in the lab

Engineers have created a chemical system that continually produces useful crude oil minutes after they pour in raw algae material — a green paste with the consistency of pea soup. The technol…

Source: Algae to crude oil: Million-year natural process takes minutes in the lab

Algae to crude oil: Million-year natural process takes minutes in the lab

Engineers have created a chemical system that continually produces useful crude oil minutes after they pour in raw algae material — a green paste with the consistency of pea soup. The technology eliminates the need to dry the algae and recycles ingredients such as phosphorus, cutting costs. The work has been licensed to a biofuels company which is working with an industrial partner to build a pilot plant.

(L-R): Algae slurry; biocrude oil; and, with further processing, refined biocrude which contains mostly the makings of gasoline and diesel fuel
Credit: Photo by PNNL

Engineers have created a continuous chemical process that produces useful crude oil minutes after they pour in harvested algae — a verdant green paste with the consistency of pea soup.

The research by engineers at the Department of Energy’s Pacific Northwest National Laboratory was reported recently in the journal Algal Research. A biofuels company, Utah-based Genifuel Corp., has licensed the technology and is working with an industrial partner to build a pilot plant using the technology.

In the PNNL process, a slurry of wet algae is pumped into the front end of a chemical reactor. Once the system is up and running, out comes crude oil in less than an hour, along with water and a byproduct stream of material containing phosphorus that can be recycled to grow more algae.

With additional conventional refining, the crude algae oil is converted into aviation fuel, gasoline or diesel fuel. And the waste water is processed further, yielding burnable gas and substances like potassium and nitrogen, which, along with the cleansed water, can also be recycled to grow more algae.

While algae has long been considered a potential source of biofuel, and several companies have produced algae-based fuels on a research scale, the fuel is projected to be expensive. The PNNL technology harnesses algae’s energy potential efficiently and incorporates a number of methods to reduce the cost of producing algae fuel.

“Cost is the big roadblock for algae-based fuel,” said Douglas Elliott, the laboratory fellow who led the PNNL team’s research. “We believe that the process we’ve created will help make algae biofuels much more economical.”

PNNL scientists and engineers simplified the production of crude oil from algae by combining several chemical steps into one continuous process. The most important cost-saving step is that the process works with wet algae. Most current processes require the algae to be dried — a process that takes a lot of energy and is expensive. The new process works with an algae slurry that contains as much as 80 to 90 percent water.

“Not having to dry the algae is a big win in this process; that cuts the cost a great deal,” said Elliott. “Then there are bonuses, like being able to extract usable gas from the water and then recycle the remaining water and nutrients to help grow more algae, which further reduces costs.”

While a few other groups have tested similar processes to create biofuel from wet algae, most of that work is done one batch at a time. The PNNL system runs continuously, processing about 1.5 liters of algae slurry in the research reactor per hour. While that doesn’t seem like much, it’s much closer to the type of continuous system required for large-scale commercial production.

The PNNL system also eliminates another step required in today’s most common algae-processing method: the need for complex processing with solvents like hexane to extract the energy-rich oils from the rest of the algae. Instead, the PNNL team works with the whole algae, subjecting it to very hot water under high pressure to tear apart the substance, converting most of the biomass into liquid and gas fuels.

The system runs at around 350 degrees Celsius (662 degrees Fahrenheit) at a pressure of around 3,000 PSI, combining processes known as hydrothermal liquefaction and catalytic hydrothermal gasification. Elliott says such a high-pressure system is not easy or cheap to build, which is one drawback to the technology, though the cost savings on the back end more than makes up for the investment.

“It’s a bit like using a pressure cooker, only the pressures and temperatures we use are much higher,” said Elliott. “In a sense, we are duplicating the process in the Earth that converted algae into oil over the course of millions of years. We’re just doing it much, much faster.”

The products of the process are:

  • Crude oil, which can be converted to aviation fuel, gasoline or diesel fuel. In the team’s experiments, generally more than 50 percent of the algae’s carbon is converted to energy in crude oil — sometimes as much as 70 percent.
  • Clean water, which can be re-used to grow more algae.
  • Fuel gas, which can be burned to make electricity or cleaned to make natural gas for vehicle fuel in the form of compressed natural gas.
  • Nutrients such as nitrogen, phosphorus, and potassium — the key nutrients for growing algae.

Elliott has worked on hydrothermal technology for nearly 40 years, applying it to a variety of substances, including wood chips and other substances. Because of the mix of earthy materials in his laboratory, and the constant chemical processing, he jokes that his laboratory sometimes smells “like a mix of dirty socks, rotten eggs and wood smoke” — an accurate assessment.

Genifuel Corp. has worked closely with Elliott’s team since 2008, licensing the technology and working initially with PNNL through DOE’s Technology Assistance Program to assess the technology.

“This has really been a fruitful collaboration for both Genifuel and PNNL,” said James Oyler, president of Genifuel. “The hydrothermal liquefaction process that PNNL developed for biomass makes the conversion of algae to biofuel much more economical. Genifuel has been a partner to improve the technology and make it feasible for use in a commercial system.

“It’s a formidable challenge, to make a biofuel that is cost-competitive with established petroleum-based fuels,” Oyler added. “This is a huge step in the right direction.”

The recent work is part of DOE’s National Alliance for Advanced Biofuels & Bioproducts, or NAABB. This project was funded with American Recovery and Reinvestment Act funds by DOE’s Office of Energy Efficiency and Renewable Energy. Both PNNL and Genifuel have been partners in the NAABB program.

A short video clip about the process is at https://www.youtube.com/watch?v=Qs0QZJ0rea0.


Story Source:

Materials provided by DOE/Pacific Northwest National Laboratory.

Technology converts human waste into bio-based fuel

Fuel from sewage is the future — and it’s closer than you think

It may sound like science fiction, but wastewater treatment plants across the United States may one day turn ordinary sewage into biocrude oil, thanks to new research. The technology, hydrothermal liquefaction, mimics the geological conditions Earth uses to create crude oil, using high pressure and temperature to achieve in minutes something that takes Mother Nature millions of years.

Biocrude oil, produced from wastewater treatment plant sludge, looks and performs virtually like fossil petroleum.
Credit: Courtesy of WE&RF

It may sound like science fiction, but wastewater treatment plants across the United States may one day turn ordinary sewage into biocrude oil, thanks to new research at the Department of Energy’s Pacific Northwest National Laboratory.

The technology, hydrothermal liquefaction, mimics the geological conditions Earth uses to create crude oil, using high pressure and temperature to achieve in minutes something that takes Mother Nature millions of years. The resulting material is similar to petroleum pumped out of the ground, with a small amount of water and oxygen mixed in. This biocrude can then be refined using conventional petroleum refining operations.

Wastewater treatment plants across the U.S. treat approximately 34 billion gallons of sewage every day. That amount could produce the equivalent of up to approximately 30 million barrels of oil per year. PNNL estimates that a single person could generate two to three gallons of biocrude per year.

Sewage, or more specifically sewage sludge, has long been viewed as a poor ingredient for producing biofuel because it’s too wet. The approach being studied by PNNL eliminates the need for drying required in a majority of current thermal technologies which historically has made wastewater to fuel conversion too energy intensive and expensive. HTL may also be used to make fuel from other types of wet organic feedstock, such as agricultural waste.

Using hydrothermal liquefaction, organic matter such as human waste can be broken down to simpler chemical compounds. The material is pressurized to 3,000 pounds per square inch — nearly one hundred times that of a car tire. Pressurized sludge then goes into a reactor system operating at about 660 degrees Fahrenheit. The heat and pressure cause the cells of the waste material to break down into different fractions — biocrude and an aqueous liquid phase.

“There is plenty of carbon in municipal waste water sludge and interestingly, there are also fats,” said Corinne Drennan, who is responsible for bioenergy technologies research at PNNL. “The fats or lipids appear to facilitate the conversion of other materials in the wastewater such as toilet paper, keep the sludge moving through the reactor, and produce a very high quality biocrude that, when refined, yields fuels such as gasoline, diesel and jet fuels.”

In addition to producing useful fuel, HTL could give local governments significant cost savings by virtually eliminating the need for sewage residuals processing, transport and disposal.

“The best thing about this process is how simple it is,” said Drennan. “The reactor is literally a hot, pressurized tube. We’ve really accelerated hydrothermal conversion technology over the last six years to create a continuous, and scalable process which allows the use of wet wastes like sewage sludge.”

An independent assessment for the Water Environment & Reuse Foundation calls HTL a highly disruptive technology that has potential for treating wastewater solids. WE&RF investigators noted the process has high carbon conversion efficiency with nearly 60 percent of available carbon in primary sludge becoming bio-crude. The report calls for further demonstration, which may soon be in the works.

PNNL has licensed its HTL technology to Utah-based Genifuel Corporation, which is now working with Metro Vancouver, a partnership of 23 local authorities in British Columbia, Canada, to build a demonstration plant.

“Metro Vancouver hopes to be the first wastewater treatment utility in North America to host hydrothermal liquefaction at one of its treatment plants,” said Darrell Mussatto, chair of Metro Vancouver’s Utilities Committee. “The pilot project will cost between $8 to $9 million (Canadian) with Metro Vancouver providing nearly one-half of the cost directly and the remaining balance subject to external funding.”

Once funding is in place, Metro Vancouver plans to move to the design phase in 2017, followed by equipment fabrication, with start-up occurring in 2018.

“If this emerging technology is a success, a future production facility could lead the way for Metro Vancouver’s wastewater operation to meet its sustainability objectives of zero net energy, zero odours and zero residuals,” Mussatto added.

In addition to the biocrude, the liquid phase can be treated with a catalyst to create other fuels and chemical products. A small amount of solid material is also generated, which contains important nutrients. For example, early efforts have demonstrated the ability to recover phosphorus, which can replace phosphorus ore used in fertilizer production.


Story Source:

Materials provided by Pacific Northwest National Laboratory

Structural similarity found in both human cells and neutron stars

Cosmic connection: How human cells are like neutron stars

We humans may be more aligned with the universe than we realize. Scientists have discovered that neutron stars and cell cytoplasm have something in common: structures that resemble multistory parking garages.

Similar shapes — structures consisting of stacked sheets connected by helical ramps — have been found in cell cytoplasm (left) and neutron stars (right).
Credit: Image courtesy of University of California – Santa Barbara

We humans may be more aligned with the universe than we realize.

According to research published in the journal Physical Review C, neutron stars and cell cytoplasm have something in common: structures that resemble multistory parking garages.

In 2014, UC Santa Barbara soft condensed-matter physicist Greg Huber and colleagues explored the biophysics of such shapes — helices that connect stacks of evenly spaced sheets — in a cellular organelle called the endoplasmic reticulum (ER). Huber and his colleagues dubbed them Terasaki ramps after their discoverer, Mark Terasaki, a cell biologist at the University of Connecticut.

Huber thought these “parking garages” were unique to soft matter (like the interior of cells) until he happened upon the work of nuclear physicist Charles Horowitz at Indiana University. Using computer simulations, Horowitz and his team had found the same shapes deep in the crust of neutron stars.

“I called Chuck and asked if he was aware that we had seen these structures in cells and had come up with a model for them,” said Huber, the deputy director of UCSB’s Kavli Institute for Theoretical Physics (KITP). “It was news to him, so I realized then that there could be some fruitful interaction.”

The resulting collaboration, highlighted in Physical Review C, explored the relationship between two very different models of matter.

Nuclear physicists have an apt terminology for the entire class of shapes they see in their high-performance computer simulations of neutron stars: nuclear pasta. These include tubes (spaghetti) and parallel sheets (lasagna) connected by helical shapes that resemble Terasaki ramps.

“They see a variety of shapes that we see in the cell,” Huber explained. “We see a tubular network; we see parallel sheets. We see sheets connected to each other through topological defects we call Terasaki ramps. So the parallels are pretty deep.”

However, differences can be found in the underlying physics. Typically matter is characterized by its phase, which depends on thermodynamic variables: density (or volume), temperature and pressure — factors that differ greatly at the nuclear level and in an intracellular context.

“For neutron stars, the strong nuclear force and the electromagnetic force create what is fundamentally a quantum-mechanical problem,” Huber explained. “In the interior of cells, the forces that hold together membranes are fundamentally entropic and have to do with the minimization of the overall free energy of the system. At first glance, these couldn’t be more different.”

Another difference is scale. In the nuclear case, the structures are based on nucleons such as protons and neutrons and those building blocks are measured using femtometers (10-15). For intracellular membranes like the ER, the length scale is nanometers (10-9). The ratio between the two is a factor of a million (10-6), yet these two vastly different regimes make the same shapes.

“This means that there is some deep thing we don’t understand about how to model the nuclear system,” Huber said. “When you have a dense collection of protons and neutrons like you do on the surface of a neutron star, the strong nuclear force and the electromagnetic forces conspire to give you phases of matter you wouldn’t be able to predict if you had just looked at those forces operating on small collections of neutrons and protons.”

The similarity of the structures is riveting for theoretical and nuclear physicists alike. Nuclear physicist Martin Savage was at the KITP when he came across graphics from the new paper on arXiv, a preprint library that posts thousands of physics, mathematics and computer science articles. Immediately his interest was piqued.

“That similar phases of matter emerge in biological systems was very surprising to me,” said Savage, a professor at the University of Washington. “There is clearly something interesting here.”

Co-author Horowitz agreed. “Seeing very similar shapes in such strikingly different systems suggests that the energy of a system may depend on its shape in a simple and universal way,” he said.

Huber noted that these similarities are still rather mysterious. “Our paper is not the end of something,” he said. “It’s really the beginning of looking at these two models.”


Story Source:

Materials provided by University of California – Santa Barbara. Original written by Julie Cohen.

How lizards regenerate their tails: Researchers discover genetic ‘recipe’

By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers is one step c…

Source: How lizards regenerate their tails: Researchers discover genetic ‘recipe’

How lizards regenerate their tails: Researchers discover genetic ‘recipe’

By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers is one step closer to solving that mystery. The scientists have discovered the genetic “recipe” for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.Arizona State University researchers discovered that green anole lizards turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing.
Credit: Joel Robertson

By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers from Arizona State University is one step closer to solving that mystery. The scientists have discovered the genetic “recipe” for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.

An interdisciplinary team of scientists used next-generation molecular and computer analysis tools to examine the genes turned on in tail regeneration. The team studied the regenerating tail of the green anole lizard (Anolis carolinensis), which when caught by a predator, can lose its tail and then grow it back.

The findings are published today in the journal PLOS ONE.

“Lizards basically share the same toolbox of genes as humans,” said lead author Kenro Kusumi, professor in ASU’s School of Life Sciences and associate dean in the College of Liberal Arts and Sciences. “Lizards are the most closely-related animals to humans that can regenerate entire appendages. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing.”

Other animals, such as salamanders, frog tadpoles and fish, can also regenerate their tails, with growth mostly at the tip. During tail regeneration, they all turn on genes in what is called the ‘Wnt pathway’ — a process that is required to control stem cells in many organs such as the brain, hair follicles and blood vessels. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.

“Regeneration is not an instant process,” said Elizabeth Hutchins, a graduate student in ASU’s molecular and cellular biology program and co-author of the paper. “In fact, it takes lizards more than 60 days to regenerate a functional tail. Lizards form a complex regenerating structure with cells growing into tissues at a number of sites along the tail.”

“We have identified one type of cell that is important for tissue regeneration,” said Jeanne Wilson-Rawls, co-author and associate professor with ASU’s School of Life Sciences. “Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues.”

“Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail,” said Kusumi. “By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future.”

The researchers hope their findings will help lead to discoveries of new therapeutic approaches to spinal cord injuries, repairing birth defects, and treating diseases such as arthritis.

The research team included Kusumi, Hutchins, Wilson-Rawls, Alan Rawls, and Dale DeNardo from ASU School of Life Sciences, Rebecca Fisher from ASU School of Life Sciences and the University of Arizona College of Medicine Phoenix, Matthew Huentelman from the Translational Genomic Research Institute, and Juli Wade from Michigan State University. This research was funded by grants from the National Institutes of Health and Arizona Biomedical Research Commission.


Story Source:

Materials provided by Arizona State University College of Liberal Arts and Sciences.

Conserved microRNAs may regulate limb regeneration in evolutionarily distant species

Regeneration in amphibian and ray-finned fish species may involve conserved microRNAs, indicate potential common regulatory process Several conserved microRNAs, or short, highly conserved noncoding…

Source: Conserved microRNAs may regulate limb regeneration in evolutionarily distant species

Conserved microRNAs may regulate limb regeneration in evolutionarily distant species

Regeneration in amphibian and ray-finned fish species may involve conserved microRNAs, indicate potential common regulatory process

Several conserved microRNAs, or short, highly conserved noncoding RNAs that are targeted to and inhibit expression of specific genes, may be involved in the regulation of limb regeneration across evolutionarily distant species.

Several conserved microRNAs, or short, highly conserved noncoding RNAs that are targeted to and inhibit expression of specific genes, may be involved in the regulation of limb regeneration across evolutionarily distant species, according to a study published June 29, 2016 in the open-access journal PLOS ONE by Benjamin King and Viravuth Yin from Mount Desert Island Biological Laboratory and the University of Maine.

Although there are species throughout the animal kingdom capable of regeneration in some capacity, this defining characteristic is not equally distributed throughout evolution. Unlike mammals, some amphibian and fish species have the ability to regenerate fully functional tissue or appendages after loss, including bone, muscle, nerves, and blood vessels. While it is known that this regeneration requires the formation of an unspecialized tissue known as “blastemal,” little is known about the genetic regulation of blastema formation.

To determine whether the genetic control of blastema formation may be conserved across species, the authors of this study conducted RNA sequencing of regenerating limb tissues from three evolutionarily distant species, one salamander and two ray-finned fish, at various times following amputation, when regeneration may be occurring.

The authors found a core group of conserved microRNAs and their posited target genes that may be involved in regulation of blastema formation in all three species, including some microRNAs not previously known to act in regeneration.


Story Source:

Materials provided by PLOS.

Limb or organ regrowth may be hidden in our genes

Genetic elements that drive regeneration uncovered

Salamanders and fish possess genes that can enable healing of damaged tissue and even regrowth of missing limbs. The key to regeneration lies not only in the genes, but in the DNA sequences that regulate expression of those genes in response to an injury. Researchers have discovered regulatory sequences that they call ’tissue regeneration enhancer elements’ or TREEs, which can turn on genes in injury sites.
The green signal in these images of an injured zebrafish heart and a fin indicate the activity of a gene that enhances tissue regeneration.
Credit: Junsu Kang, Duke University

If you trace our evolutionary tree way back to its roots — long before the shedding of gills or the development of opposable thumbs — you will likely find a common ancestor with the amazing ability to regenerate lost body parts.

Lucky descendants of this creature, including today’s salamanders or zebrafish, can still perform the feat, but humans lost much of their regenerative power over millions of years of evolution.

In an effort to understand what was lost, researchers have built a running list of the genes that enable regenerating animals to grow back a severed tail or repair damaged tissues. Surprisingly, they have found that genes important for regeneration in these creatures also have counterparts in humans. The key difference might not lie in the genes themselves but in the sequences that regulate how those genes are activated during injury.

A Duke study appearing April 6 in the journal Nature has discovered the presence of these regulatory sequences in zebrafish, a favored model of regeneration research. Called “tissue regeneration enhancer elements” or TREEs, these sequences can turn on genes in injury sites and even be engineered to change the ability of animals to regenerate.

“We want to know how regeneration happens, with the ultimate goal of helping humans realize their full regenerative potential,” said Kenneth D. Poss, Ph.D., senior author of the study and professor of cell biology at Duke University School of Medicine. “Our study points to a way that we could potentially awaken the genes responsible for regeneration that we all carry within us.”

Over the last decade, researchers have identified dozens of regeneration genes in organisms like zebrafish, flies, and mice. For example, one molecule called neuregulin 1 can make heart muscle cells proliferate and others called fibroblast growth factors can promote the regeneration of a severed fin. Yet, Poss says, what has not been explored are the regulatory elements that turn these genes on in injured tissue, keep them on during regeneration, and then turn them off when regeneration is done.

In this study, Poss and his colleagues wanted to determine whether or not these important stretches of DNA exist, and if so, pinpoint their location. It was already well known that small chunks of sequence, called enhancer elements, control when genes are turned on in a developing embryo. But it wasn’t clear whether these elements are also used to drive regeneration.

First, lead study author Junsu Kang, Ph.D., a postdoctoral fellow in the Poss lab, looked for genes that were strongly induced during fin and heart regeneration in the zebrafish. He found that a gene called leptin b was turned on in fish with amputated fins or injured hearts. Kang scoured the 150,000 base pairs of sequence surrounding leptin b and identified an enhancer element roughly 7,000 base pairs away from the gene.

He then whittled the enhancer down to the shortest required DNA sequence. In the process, Kang discovered that the element could be separated into two distinct parts: one that activates genes in an injured heart, and, next to it, another that activates genes in an injured fin. He fused these sequences to two regeneration genes, fibroblast growth factor and neuregulin 1, to create transgenic zebrafish whose fins and hearts had superior regenerative responses after injury.

Finally, the researchers tested whether these “tissue regeneration enhancer elements” or TREEs could have a similar effect in mammalian systems like mice. Collaborator Brian L. Black, PhD, of the University of California, San Francisco attached one TREE to a gene called lacZ that produces a blue color wherever it is turned on. Remarkably, he found that borrowing these elements from the genome of zebrafish could activate gene expression in the injured paws and hearts of transgenic mice.

“We are just at the beginning of this work, but now we have an encouraging proof of concept that these elements possess all the sequences necessary to work with mammalian machinery after an injury,” said Poss. He suspects there may be many different types of TREEs: those that turn on genes in all tissues; those that turn on genes only in one tissue like the heart; and those that are active in the embryo as it develops and then are reactivated in the adult as it regenerates.

Eventually, Poss thinks that genetic elements like these could be combined with genome-editing technologies to improve the ability of mammals, even humans, to repair and regrow damaged or missing body parts.

“We want to find more of these types of elements so we can understand what turns on and ultimately controls the program of regeneration,” said Poss. “There may be strong elements that boost expression of the gene much higher than others, or elements that activate genes in a specific cell type that is injured. Having that level of specificity may one day enable us to change a poorly regenerative tissue to a better one with near-surgical precision.”

The Nature study was supported by an American Heart Association (AHA) postdoctoral fellowship (12POST11920060), a National Institutes of Health (NIH) Clinical Investigator Award (K08 HL116485), a National Science Foundation (NSF) Graduate Research Fellowship (1106401), a NIH postdoctoral fellowship (F32 HL120494) and by grants from the NIH (R01 HL089707, R01 HL064658, R01 GMO74057, and R01 HL081674). Additional support came from the Howard Hughes Medical Institute (HHMI).


Story Source:

Materials provided by Duke University.

Regeneration: what does it mean and how does it work?

By Elly Tanaka

Some parts of our bodies can repair themselves quite well after injury, but others don’t repair at all. We certainly can’t regrow a whole leg or arm, but some animals CAN regrow – or regenerate – whole body parts. So what can we learn from these regenerative animals?

Did you know?

A young salamander can regrow a whole leg in about five weeks.

The human liver can regrow after damage

The human liver can regrow after damage

The planarian can regenerate from either a head or a tail piece

The planarian can regenerate from either a head or a tail piece

The salamander can regenerate the limb, heart, tail, brain, eye tissues, kidney, brain and spinal cord throughout life

The salamander can regenerate the limb, heart, tail, brain, eye tissues, kidney, brain and spinal cord throughout life

Cross-section of a regenerating salamander limb; Green = limb muscle fibers; Red = skin

Cross-section of a regenerating salamander limb; Green = limb muscle fibers; Red = skin

Zebrafish can regenerate heart tissue without relying on stem cells

Zebrafish can regenerate heart tissue without relying on stem cells

Regeneration and humans

Regeneration means the regrowth of a damaged or missing organ part from the remaining tissue. As adults, humans can regenerate some organs, such as the liver. If part of the liver is lost by disease or injury, the liver grows back to its original size, though not its original shape. And our skin is constantly being renewed and repaired. Unfortunately many other human tissues don’t regenerate, and a goal in regenerative medicine is to find ways to kick-start tissue regeneration in the body, or to engineer replacement tissues.

Regenerating animals

There are many animals that can regenerate complex body parts with full function and form after amputation or injury. Invertebrates (animals without a spinal cord) such as the flatworm or planarian can regenerate both the head from a tail piece, and the tail from a head piece. Among vertebrates (animals with a spinal cord), fish can regenerate parts of the brain, eye, kidney, heart and fins. Frogs can regenerate the limb, tail, brain and eye tissue as tadpoles but not as adults. And salamanders can regenerate the limb, heart, tail, brain, eye tissues, kidney, brain and spinal cord throughout life.

How do these regenerative animals regrow such complex structures? After amputation, stem cells accumulate at the injury site in a structure called the blastema. An important subject of ongoing research is how signals from the injury site cause the stem cells to form the blastema and start dividing to rebuild the missing part. And what about the stem cells themselves? Do the animals use a single type of stem cell in the blastema that can differentiate into many different types of tissues (called a multipotent stem cell). Or is a separate set of stem cells responsible for making each of the different tissues needed to make up the new body part?

Possibilities for regrowing a limb: Is one kind of stem cell responsible for making all the different tissues needed (A)? Or is there a separate set of stem cells responsible for making each of the different tissues?Possibilities for regrowing a limb: Is one kind of stem cell responsible for making all the different tissues needed (A)? Or is there a separate set of stem cells responsible for making each of the different tissues?

Understanding how regeneration works

Recent research in different regenerating animals has shown that there are various stem cell strategies for regenerating body parts built from multiple tissues, such as muscle, nerve and skin. If we understand the principles and molecules these animals use to regenerate adult tissues, can these lessons be applied to regenerating or engineering human tissue?

Scientist Peter Reddien’s research group in the USA recently solved a long-standing question in planarian (flatworm) regeneration – can a single stem cell regenerate a whole animal? The answer is yes, it can. This shows that adult planaria have pluripotent stem cells – cells that can make ALL the cell types of the animal’s body. How these pluripotent cells are controlled in the flatworm’s body so that they do not form tumors is an important question that several research groups are now studying.

But not all animals use pluripotent cells in regeneration. The stem cells that regenerate a frog tail and a salamander limb have very different properties from a planarian stem cell. In these animals, each tissue – such as muscle, nerve, or skin – has its own set of stem cells that just make the different types of cells in that particular tissue. In other words, a muscle stem cell cannot make skin and skin stem cells can’t make muscle. These multipotent tissue-specific stem cells are probably very similar to the stem cells in our own bodies that renew or repair tissues such as our skin or muscle. Why can such stem cells regenerate an entire limb in a salamander, but only repair damage to a single tissue type in our own bodies? This is another question that scientists are working on now.

Salamander limb regeneration: Salamanders use tissue-specific stem cells to regrow damaged limbs - each stem cell can only make cells belonging to one tissueSalamander limb regeneration: Salamanders use tissue-specific stem cells to regrow damaged limbs – each stem cell can only make cells belonging to one tissue

As well as using stem cells, regeneration can work by causing differentiated cells that had stopped dividing to ‘go back’ to dividing and multiplying in order to replace the lost tissue. This has recently been shown to happen in heart regeneration in zebrafish, where a heart muscle cell called the cardiomyocyte divides to replenish missing cardiac tissue. This regenerative phenomenon has also been found in newly born mouse hearts, but is rapidly lost as the mice mature. More research is needed to understand how differentiated cells can be made to divide and produce new heart tissue, and why this capacity is lost in humans.

Future research and regenerative medicine

By defining the properties of stem cells that regenerate complex body parts, scientists are learning how injury causes these stem cells to regenerate the missing part instead of just forming scar tissue. Future research may make it possible to apply this knowledge in new kinds of medical treatments.

Pluripotent stem cells
How similar are the pluripotent stem cells of the planarian to mammalian embryonic stem cellsor induced pluripotent stem cells? By studying the planarian, maybe we will gain insight into how to control human embryonic stem cells to replace parts of our own bodies.

Tissue stem cells
Salamanders and frogs use tissue stem cells that may be much like our own, so why can they regenerate a whole limb whereas we form scars? Ongoing research indicates that regenerative animals keep a kind of map inside their adult tissues, telling cells where they are and what they should be. Parts of this map may have been lost in mammals, or perhaps our stem cells have lost the ability to read the map. Researchers hope to find out what exactly is missing or blocked in mammals, and whether such information can be restored to direct stem cells to take part in regeneration for medical applications.

Differentiated cells
Can we make adult, differentiated cells like heart muscle cells start dividing again, as in the zebrafish? It will be important to find out why mammalian heart cells lose this ability, and if it can be restored.

http://www.eurostemcell.org/factsheet/regeneration-what-does-it-mean-and-how-does-it-work