embryonic stem cells : NPR

A human embryo kept alive in the lab for 12 days begins to show signs of early development. The green cells seen here in the center would go on to form the body. This embryo is in the process of twinning, forming two small spheres out of one. Courtesy of Gist Croft, Cecilia Pellegrini, Ali Brivanlou/Rockefeller University hide caption

Four sheep cloned from the same genetic material as Dolly roam the paddocks in Nottingham, England. The University of Nottingham hide caption

Ken (left) and Henry were created using DNA plucked from a skin cell of Melvin, the beloved pet of Paula and Phillip Dupont of Lafayette, La. Edmund D. Fountain for NPR hide caption

In 1954, Dr. Frederick C. Robbins, then chief of pediatrics and contagious diseases at Cleveland Metropolitan General Hospital, was one of three winners of that year's Nobel Prize in medicine. The scientists' work, which led to a vaccine against polio, was performed in human fetal cells. AP hide caption

Ryoji Noyori, a Nobel Prize-winning chemist and president of Japan's prestigious RIKEN research institute, bows at a news conference in Tokyo Tuesday to apologize for the scientific misconduct of a RIKEN colleague. Eugene Hoshiko/AP hide caption

A mouse embryo grows from stem cells made by stressing blood cells with acid. The blood cells are tagged with a protein that creates green light. Courtesy of Haruko Obokata hide caption

After President Obama overturned Bush-era policy restricting federal funding of embryonic stem cell research in 2009, Nebraska Right to Life led a protest of the research outside the University of Nebraska regents' meeting. Nati Harnik/AP hide caption

Human embryos grow in a petri dish two days after scientists in Oregon cloned them from a donor's skin cell. http://www.flickr.com/photos/ohsunews/8726915230/in/photostream//Courtesy of OHSU Photos hide caption

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Injections of Vitamin C Could Help Fight Blood Cancer – Wall Street Pit

According to the Leukemia & Lymphoma Society (LLS), one person in the United States is diagnosed with a blood cancer every 3 minutes. One person dies approximately every 9 minutes due to this illness.

Blood cancers affect the blood, bone marrow, and lymphatic system. Most of these cancers originate in the bone marrow where new blood cells are produced. .

Our bone marrow produces three types of blood cells: red blood cells, white blood cells, and platelets. However, cancer in the blood occurs when an abnormal type of blood cell goes into an uncontrolled growth and disrupts the normal blood cell development.

The three main types of blood cancers are:

Now, theres news that vitamin C can help fight blood cancer.

Luisa CimminoandBenjamin Neelat the New York University School of Medicine and their colleagues have discovered that, by injecting vitamin C, cancer growth could be prevented.

According to the researchers, blood cancers like acute and chronic leukemia are caused by the mutation of a gene called tet methylcytosine dioxygenase 2 or TET2. This gene is responsible for ensuring the healthy growth of certain stem cells for the production of white blood cells. But, when TET2 mutation occurs, cell growth goes haywire and leads to cancer.

In their mice experiment, the animals were given variableTET2function through genetic engineering. The researchers discovered that cancer is induced with 50 per cent reduction in TET2 activity, and it continues to develop when the said gene remained at a low level.

However, when TET2 was restored, the gene stopped the uncontrolled growth and killed the cancerous cells.

After such findings, what the team needed to find next was something to reactivate TET2. And they opted to use vitamin C, which has the potency to affect embryonic stem cells.

For 24 weeks, they injected a group of mice which had low TET2 with very high dose of vitamin C daily. This slowed the progression of blood cancer. But, in the case of another group of mice which did not receive vitamin C injections, they showed signs of developing leukemia.

Moreover, to test the efficacy of vitamin C, the researchers added it to a cancer drug to which they exposed human leukemia cells in a lab dish. It proved very effective.

With this discovery, the team is hoping that vitamin C would be used in cancer therapies. It would especially help older people with blood cancer whose immune system are too weak to undergo chemotherapy. But, this would have to be done intravenously. Just taking in large doses of vitamin C would not prevent cancer since the body excretes it through urine when its already above 500 milligrams.

Still, this is a very important study that will definitely have a very lasting impact on the field, notes Ulrich Steidl of the Albert Einstein College of Medicine, adding that it will likely inspire a lot of scientists and translational investigators to think about similar strategies and to go after these pre-leukemic stem cells, which, in [Steidls] opinion will be critical if were ultimately aiming for a cure.

For healthy people, or those who want to boost their immune system, experts recommend taking vitamin C supplements twice a day for better absorption.

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Injections of Vitamin C Could Help Fight Blood Cancer - Wall Street Pit

Letter: Response to ‘Disappointed by Republicans’ – The Herald-News

To the Editor:

This is in response to Renee Klugmans Aug. 9 letter Disappointed by Republicans. I think Democrats, not Republicans, lost their soul.

Democrats are now the party of baby butchers, socialists, anti-freedom of speech, illegal immigration, anti-traditional family, and pro-sexual perversion.

Republican free-market policies raise everyones standard of living while Democrats socialism leads to more poverty and loss of freedom. Everyone agrees with having a safety net for those overtaken by adversity. But welfare as a way of life is inappropriate and harmful, perpetuating poverty and dependency.

The history of racism belongs to Democrats. The goal of the KKK was overthrow of Republican state governments in the South. The emancipation proclamation was favored by Republicans and opposed by Democrats.The 1964 Civil Rights Act was approved by 80 percent of Republicans and only 60 percent of Democrats.

Voter IDs cost little or nothing and keep no one from voting. People opposed to voter integrity want voter fraud.

Evangelicals voted for Trump as the lesser of two evils. Trump is appointing conservative judges to uphold the Constitution protecting freedom of religion.

I have degrees in physics and nuclear engineering, and an MBA. I like college and science.

The problem is many colleges today indoctrinate the students in Marxist and anti-American ideology while suppressing conservative and Christian speech.

They promote a lot of bad science like evolution, man-made climate change, and use of embryonic stem cells while squelching opposing facts. True science should be open to questioning and alternative ideas.

Please note the Social Security Trust Fund has zero real money because of lying liberals in both parties.

I am disappointed in the Democrats and establishment Republican politicians like Paul Ryan and Mitch McConnell. Trump was voted in to drain the swamp and the swamp creatures are fighting it.

Robert C. Lemke

Joliet

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Letter: Response to 'Disappointed by Republicans' - The Herald-News

What are Embryonic Stem Cells? – amaskincare.com

Essentially all of the Cells of aDeveloping Embryo are Stem Cells

Embryonic stem cells are derived from embryos before to the 2nd week of development long before the developing embryo has transitioned to becoming a Fetus. During these first two weeks, essentially all of the cells of the embryo are stem cells, in that they have not differentiated into cells with specialized functions. Typically embryonic stem cells are derived from embryos that are created in laboratory conditions, not harvested directly from a human mother. In other words, a human egg has been harvested from a woman and fertilized with a human sperm in vitro (in a laboratory). Thus usually takes place in an in vitro fertilization clinicand then donated for research purposes.

The technique of growing cells in the laboratory is referred to as cell culture. Human embryonic stem cells (hESCs) are grown by harvesting the cells derived from an early stage preimplantation embryo (a very young embryo that if present in a human mother would not yet be implanted in her uterus). These cells are grown in a special laboratory dish that contains a nutrient broth known as culture medium.

Once the cells have taken hold and are surviving they can be removed and placed into several additional culture dishes. The process is called sub-culturing the cells and can be repeated many times over many weeks and months. Each cycle of sub-culturing the cells is referred to as a passage, and is a way that a few original stem cells can be expanded into many generations and millions of stem cells and are referred to as an embryonic stem cell line.

During the process of generating lines of embryonic stem cells in laboratory conditions, it is important to test the cells to see if they exhibit the basic properties or characteristics of stems cells. This process is called characterization.

Though this process has not been standardized throughout the cell-biology industry, the following are some of the tests that are commonly performed:

Perhaps an even better question to ask is how do we induce stem cells to differentiate into the exact tissue or organ we need?

Let me explain. Obviously, the holy grail of regenerative medicine and stem cell therapy would be to grow a new organ lets say a liver for a patient who has a diseased liver. In such a world, any damaged or diseased organ could simply be replaced by a new young organ generated right from the patients own stem cells.

The hope is that by changing the composition of the nutrient base in which the cells are cultivated, or by adding certain transcription factors, or by using any number of chemical, biochemical and electronic elements, we might find the correct recipe for inducing a stem cell to differentiate into the cells we need or want. Though we have discovered some basic protocols for limited induction of stem cells into specific organ tissues, we are far from growing a complete and viable human organ.

To date our best hope is focusing on developing a specific cell type and not the entire organ. For example the cells that produce insulin within a pancreas, but not the entire pancreas.

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What are Embryonic Stem Cells? - amaskincare.com

Woman Will Use Stem Cells From Her Baby’s Umbilical Cord To … – LifeNews.com

A pregnant British mom hopes she and her unborn baby will be the answer to help prolong her ailing brothers life.

Georgina Russell, of Preston, England, said she was desperate to help her brother, Ashley, when doctors diagnosed him with a slow-growing but deadly brain tumor earlier this year, according to the Daily Mail.

Georgina said she began researching his condition, glioblastoma, online and looking for answers that could save his life. She found one: her pregnancy.

Stem cells produced in the umbilical cord between her and her unborn baby potentially could be used in a treatment to shrink Ashleys tumor, according to the report. Once Georgina gives birth, she said doctors will be able to harvest and store the stem cells until Ashley needs them.

There is no harm to the baby or the mother when doctors harvest stem cells from the umbilical cord unlike embryonic stem cells, which only can be taken by killing a human life in the embryonic stage.

Georgina told the Mail: The blood from the cord is being used in trials across the world. It can do amazing things to help the body repair itself. If we store the stem cells, they can be kept to be used throughout Ashleys treatment when he needs them.

They might be able to inject them into the spinal fluid, to shrink the tumour on the brain, or they may be able to use the tissue grown from them to repair any damage to other parts of his body, if he has to have chemotherapy or radiotherapy.

Ashley Russell, a British military veteran, husband and father, said doctors found the tumor after he began suffering from headaches, dizzy spells and mini-seizures about six months ago. Later, he said he also began having blurred vision. Doctors ran a series of tests before discovering the tumor on his brain.

He said doctors suggested surgery, but the procedure has high risks. They gave him about five years to live, according to the report.

Georgina said she was devastated for her brother and his family, and she began researching ways to help him. In her research online, she said she discovered how stem cells collected from the umbilical cord are helping to treat people with tumors and other diseases.

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Her brother said the idea seemed odd at first, but he is willing to try anything.

I am quite a positive person so although the diagnosis was difficult, I am determined to do whatever I can to keep going, Ashley said. I did think about not being around to see my little girl get married and knew that if there was anything that might help, I would give it a go.

Georgina currently is 33 weeks pregnant with her unborn child, the report states.

Stem cells are so powerful and his new niece or nephew could save his life, she said.

The family set up a JustGiving page to help pay for the storage of the stem cells and Ashleys treatment.

Adult stem cells and those from umbilical cords are proving to be live-saving, while life-destroying embryonic stem cells have not been effective.

David Prentice, vice president and research director for the Charlotte Lozier Institute, explained more about the effectiveness of these life-saving stem cells in 2014:

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Umbilical cord blood stem cells have become an extremely valuable alternative to bone marrow adult stem cell transplants, ever since cord blood stem cells were first used for patients over 25 years ago. The first umbilical cord blood stem cell transplant was performed in October 1988, for a 5-year-old child with Fanconi anemia, a serious condition where the bone marrow fails to make blood cells. That patient is currently alive and healthy, 25 years after the cord blood stem cell transplant.

Prentice said more than 30,000 cord blood stem cell transplants have been done across the world. These stem cells have helped treat people with blood and bone marrow diseases, leukemia and genetic enzyme diseases, he said.

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Woman Will Use Stem Cells From Her Baby's Umbilical Cord To ... - LifeNews.com

Stem cells mimic sphere where embryos grow – Futurity: Research News

Researchers report that they have coaxed pluripotent human stem cells to grow on a specially engineered surface into structures that resemble the amniotic sac.

Gumucio likens a PASE to a mismatched plastic Easter egg or a blue-and-red Pokmon ballwith two clearly divided halves of two kinds of cells

The first few weeks after sperm meets egg still hold many mysteries. Among them: what causes the process to fail, leading to many cases of infertility. Despite the importance of this critical stage, scientists havent had a good way to explore what can go wrong, or even what must go right, after the newly formed ball of cells implants in the wall of the human uterus.

But the new achievement with human stem cells may help change that. The tiny lab-grown structures could give researchers a chance to see what they couldnt before, while avoiding ethical issues associated with studying actual embryos.

The stem cells researchers used spontaneously developed some of the same structural and molecular features seen in a natural amniotic sac, which is an asymmetric, hollow ball-like structure containing cells that will give rise to a part of the placenta as well as the embryo itself.

But the structures lack other key components of the early embryo, so they cant develop into a fetus.

Its the first time a team has grown such a structure starting with stem cells, rather than coaxing a donated embryo to grow, as a few other teams have done.

As many as half of all pregnancies end in the first two weeks after fertilization, often before the woman is even aware she is pregnant. For some couples, there is a chronic inability to get past these critical early developmental steps, but we have not previously had a model that would allow us to explore the reasons why, says co-senior author Deborah Gumucio, professor of cell and developmental biology and professor of internal medicine at the University of Michigan.

We hope this work will make it possible for many scientists to dig deeper into the pathways involved in normal and abnormal development, so we can understand some of the most fascinating biology on earth.

The researchers have dubbed the new structure a post-implantation amniotic sac embryoid, or PASE. They describe how a PASE develops as a hollow spherical structure with two distinct halves that remain stable even as cells divide.

One half is made of cells that will become amniotic ectoderm, the other half consists of pluripotent epiblast cells that in nature make up the embryonic disc. The hollow center resembles the amniotic cavitywhich in normal development eventually gives rise to the fluid-filled sac that protects and cushions the fetus during development.

Gumucio likens a PASE to a mismatched plastic Easter egg or a blue-and-red Pokmon ballwith two clearly divided halves of two kinds of cells that maintain a stable form around a hollow center.

The team also reports details about the genes that became activated during the development of a PASE, and the signals that the cells in a PASE send to one another and to neighboring tissues. They show that a stable two-halved PASE structure relies on a signaling pathway called BMP-SMAD thats known to be critical to embryo development.

Gumucio says that the PASE structures even exhibit the earliest signs of initiating a primitive streak, although it did not fully develop. In a human embryo, the streak would start a process called gastrulation. Thats the division of new cells into three cell layersendoderm, mesoderm, and ectodermthat are essential to give rise to all organs and tissues in the body.

Besides working with genetic and infertility specialists to delve deeper into PASE biology as it relates to human infertility, the research team is hoping to explore additional characteristics of amnion tissue.

For example, early rupture of the amnion tissue can endanger a fetus or be the cause of a miscarriage. The team also intends to study which aspects of human amnion formation also occur in development of mouse amnion. The mouse embryo model is very attractive as an in vivo model for investigating human genetic diseases.

The research appears in the journal Nature Communications.

The teams work is overseen by a panel that monitors all work done with pluripotent stem cells at the university, and the studies are performed in accordance with laws regarding human stem cell research. The team ends experiments before the balls of cells effectively reach 14 developmental days, the cutoff used as an international limit on embryo researcheven though the work involves tissue that cannot form an embryo.

Some of the stem cell lines were derived at the University of Michigans privately funded MStem Cell Laboratory for human embryonic stem cells and the universitys Pluripotent Stem Cell Core.

The National Institutes of Health and the universitys Mechanical Engineering Startup Fund as well as the Rackham Predoctoral Fellowship funded the research. The team has worked with the universitys Office of Technology Transfer to apply for a patent on the method of generating amnion, for potential commercial use in wound healing.

Source: University of Michigan

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Stem cells mimic sphere where embryos grow - Futurity: Research News

Vitamin C helps genes to kill off cells that would cause cancer – New Scientist

Could vitamin C help drugs fight leukaemia?

Steve Gschmeissner/SPL/Getty

By Aylin Woodward

Injections of vitamin C could be a way to help fight blood cancer. Experiments in mice suggest that the nutrient helps tell out-of-control cells to stop dividing and die.

Some blood cancers, including acute and chronic leukaemia, often involve mutations affecting a gene called TET2. This gene usually helps ensure that a type of stem cell matures properly to make white blood cells, and then eventually dies. But when TET2 mutates, these cells can start dividing uncontrollably, leading to cancer. Mutations in TET2 are involved in around 42,500 cancers in the US a year.

Luisa Cimmino and Benjamin Neel at the New York University School of Medicine and their colleagues have genetically engineered mice to have variable TET2 function. They found that a 50 per cent reduction in TET2 activity can be enough to induce cancer, but that TET2 activity needs to remain low if the disease is to continue developing. If we genetically restore TET2, it blocks unhealthy replication and kills the cells, says Cimmino.

Next, the team turned to vitamin C, because it is known to have an effect in embryonic stem cells, where it can activate TET2 and help keep cell replication in check.

The team injected mice with low TET2 activity with very high doses of vitamin C every day for 24 weeks and found that it slowed the progression of leukaemia. By the end of this period, a control group that got no injections had three times as many white blood cells a sign of pre-leukaemia.

When the team exposed human leukaemia cells in a dish to a cancer drug, they found they got better results when they added vitamin C.

Neel hopes that high doses of vitamin C will eventually be incorporated into cancer therapies. People who have acute myeloid leukemia are often of advanced age, and may die from chemotherapy. Vitamin C in combination with cancer drugs may provide an alternative approach.

But taking large amounts of vitamin C is unlikely to prevent you from getting cancer, says Neel. The mice were given 100 milligrams of vitamin C in each injection, the equivalent of about two oranges. But the average person weighs about 3000 times as much as a mouse. Because the body stops taking in the vitamin after around 500 milligrams, any therapies would need to supply vitamin C intravenously. You cant get the levels of it necessary to achieve the effects in this study by eating oranges, he says.

Journal reference: Cell, DOI: 10.1026/j.cell.2017.07.032

Read more: Choosing alternative cancer treatment doubles your risk of death

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Vitamin C helps genes to kill off cells that would cause cancer - New Scientist

A way to stabilize haploidy in animal cells – Phys.Org

August 15, 2017 SKY analysis of haploid and diploid cells. Credit: CNIO

The emergence in recent years of the first mammalian haploid cell lines has raised great expectations in the scientific community. Despite their potential, these cultures present some issues that complicate their use because haploidy is unstable and can be lost quickly. The Genomic Instability Group at the Spanish National Cancer Research Centre (CNIO) has offered an explanation of this phenomenon and proposes a way to overcome it. This work has been published in the journal Proceedings of the National Academy of Sciences (PNAS).

With the exception of the sperm or ovules, cells contain two sets of chromosomes, one from each parent. However, organisms with a single set of chromosomes (haploids), such as yeast, are extremely useful for genetic studies and are crucial in identifying key genes and pathways. Laboratory yeasts enabled studies on autophagy by Yoshinori Ohsumi, which earned him the Nobel Prize in Medicine in 2016, and the Nobel-winning discovery of the cell cycle regulatory genes.

"As [yeast] has only one set of chromosomes, it is very easy to find interesting mutants, as all you have to do is to alter a single allele to produce a phenotype," says Oscar Fernndez-Capetillo, head of the Genomic Instability Group and the leader of the research project. "In mammals, in the absence of haploid cells, other approaches have been used to identify key genes, such as interfering RNA, but they are sub-optimal methods. All this changed five years ago when haploid cells were discovered in a leukaemia patient (KBM7 and HAP1) and with the emergence of techniques to create mammalian haploid embryonic stem cells, developed originally by Anton Wutz," continues Fernndez-Capetillo.

However, the cultures of such mammalian haploid cells become diploid within a few days. This phenomenon, which has been called "diploidization," is what Fernndez-Capetillo's group has been studying. Their findings suggest that the loss of haploid cells is due to their limited viability, and therefore, they are replaced by existing diploid cells in the cultures.

"When you try to isolate haploid cells, it is very difficult to take only one; you usually separate several so you always drag along a diploid. When you culture them, you invariably observe that the haploid cells die and the diploid cells become the majority," he says. "We now know that this happens because the haploid cells activate death mechanisms via p53."

Their studies show that the problem arises when the haploid cells try to separate their chromosomes during mitosis. The machinery involved in cell division has been designed to handle a fixed amount of DNA (46 chromosomes). When there is more (polyploidy) or less (haploidy), mitosis is more prone to errors during the segregation of the chromosomes, and this activates p53. This is the reason why haploid cell cultures do not thrive. By eliminating p53, as this study demonstrates, haploid cells are able to survive.

"Our findings should facilitate the use of animal haploid cells, making them accessible to a broader range of laboratories and technologies," the authors conclude. Currently, the group is trying to discover chemical forms of stabilizing haploidy in animal cells and is exploring strategies that would allow the creation of organs or even animals that only have a maternal set of chromosomes.

Explore further: First 'haploid' human stem cells could change the face of medical research

More information: A p53-dependent response limits the viability of mammalian haploid cells Proceedings of the National Academy of Sciences (2017). http://www.pnas.org/cgi/doi/10.1073/pnas.1705133114

Journal reference: Proceedings of the National Academy of Sciences

Provided by: Centro Nacional de Investigaciones Oncolgicas

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A way to stabilize haploidy in animal cells - Phys.Org

First implants derived from stem cells to ‘cure’ type 1 diabetes – New Scientist

Stem cells have been cultured to treat many different of conditions

Lewis Houghton/Science Photo Library

By Andy Coghlan

Last week, two people with type 1 diabetes became the first to receive implants containing cells generated from embryonic stem cells to treat their condition. The hope is that when blood sugar levels rise, the implants will release insulin to restore them to normal.

About 10 per cent of the 422 million people who have diabetes worldwide have type 1 diabetes, which is caused by the bodys immune system mistakenly attacking cells in the pancreas that make insulin. For more than 15 years, researchers have been trying to find a way to use stem cells to replace these, but there have been several hurdles not least, how to get the cells to work in the body.

Viacyte, a company in San Diego, California, is trying a way to get round this. The firms credit-card-sized implant, called PEC-Direct, contain cells derived from stem cells that can mature inside the body into the specialised islet cells that get destroyed in type 1 diabetes.

The implant sits just below the skin, in the forearm, for example, and is intended to automatically compensate for the missing islet cells, releasing insulin when blood sugar levels get too high.

If it works, we would call it a functional cure, says Paul Laikind, of Viacyte. Its not truly a cure because we wouldnt address the autoimmune cause of the disease, but we would be replacing the missing cells.

A similardevice has already been safety tested in 19 people with diabetes, using smaller numbers of cells. Once implanted, the progenitor cells housed in the device did mature into islet cells, but the trial didnt use enough cells to try to treat the condition.

Now Viacyte has implanted PEC-Direct packages containing the cells into two people with type 1 diabetes. A third person will also get the implant in the near future. Once inside the body, pores in the outer fabric of the device allow blood vessels to penetrate inside, nourishing the islet progenitor cells. Once these cells have matured which should take about three months the hope is that they will be able to monitor sugar levels in the blood, and release insulin as required.

If effective, it could free people with type 1 diabetes from having to closely monitor their blood sugar levels and inject insulin, although they would need to take immunosuppressive drugs to stop their bodies from destroying the new cells.

If successful, this strategy could really change the way we treat type 1 diabetes in the future, says Emily Burns of the charity Diabetes UK. A similar way to treat the condition with pancreas cells from organ donors has been in use for nearly 20 years, successfully freeing recipients from insulin injections, but a shortage of donors limits how many people are able to have this treatment.

This isnt a problem with stem cells. The embryonic stem cells used to make the progenitor cells originally came from a spare early stage embryo donated by a woman who was having IVF. Because embryonic stem cells, and the progenitor cells made from them, can be multiplied in limitless amounts, Laikind says that, if the treatment works, the method would be able to treat everyone who has the condition.

A limitless source of human insulin-producing cells would be a major step forward on the journey to a potential cure for diabetes, says James Shapiro at the University of Alberta, Canada, who has collaborated with Viacyte on this project, and who pioneered the donor pancreas method decades ago. For sure, this will in the end prove to be a durable landmark for progress in diabetes care.

Correction: This article has been updated to clarify that the cells used in this study are derived from stem cells, and to correct the size of the implanted pouch.

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First implants derived from stem cells to 'cure' type 1 diabetes - New Scientist

Lego-Like Brain Balls Could Build a Living Replica of Your Noggin – WIRED

This cerebral organoid, or mini-brain, was grown in a laboratory. It contains a diversity of cell types and internal structures that can make it a good stand-in for an actual brain in experiments. Unpredictable variations and deficiencies have hampered the organoids usefulness in research, but new techniques for creating mini-brains may change that.

Hoffman-Kim lab/Brown University

The human brain is routinely described as the most complex object in the known universe. It might therefore seem unlikely that pea-size blobs of brain cells growing in laboratory dishes could be more than fleetingly useful to neuroscientists. Nevertheless, many investigators are now excitedly cultivating these curious biological systems, formally called cerebral organoids and less formally known as mini-brains. With organoids, researchers can run experiments on how living human brains developexperiments that would be impossible (or unthinkable) with the real thing.

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

The cerebral organoids in existence today fall far short of earning the brain label, mini or otherwise. But a trio of recent publications suggests that cerebral-organoid science may be turning a cornerand that the future of such brain studies may depend less on trying to create tiny perfect replicas of whole brains and more on creating highly replicable modules of developing brain parts that can be snapped together like building blocks. Just as interchangeable parts helped make mass production and the Industrial Revolution possible, organoids that have consistent qualities and can be combined as needed may help to speed a revolution in understanding how the human brain develops.

In 2013 Madeline Lancaster , then of the Austrian Academy of Sciences, created the first true cerebral organoids when she discovered that stem cells growing in a supportive gel could form small spherical masses of organized, functioning brain tissue. Veritable colleges of mini-brains were soon thriving under various protocols in laboratories around the world.

Much to the frustration of impatient experimentalists, however, the mini-brains similarity to the real thing only went so far. Their shrunken anatomies were distorted; they lacked blood vessels and layers of tissue; neurons were present but important glial cells that make up the supportive white matter of the brain were often missing.

Worst of all was the organoids inconsistency: They differed too much from one another. According to Arnold Kriegstein , director of the developmental and stem cell biology program at the University of California, San Francisco, it was difficult to get organoids to turn out uniformly even when scientists used the same growth protocol and the same starting materials. And this makes it very difficult to have a properly controlled experiment or to even make valid conclusions, he explained.

Researchers could reduce the troublesome variability by treating early-stage organoids with growth factors that would make them differentiate more consistently as a less varied set of neurons. But that consistency would come at the expense of relevance, because real brain networks are a functional quilt of cell typessome of which arise in place while others migrate from other brain regions.

For example, in the human cortex, about 20 percent of the neuronsthe ones called interneurons, which have inhibitory effectsmigrate there from a center deeper down in the brain called the medial ganglionic eminence (MGE). An oversimplified organoid model for the cortex would be missing all those interneurons and would therefore be useless for studying how the developing brain balances its excitatory and inhibitory signals.

A stained cross section through one of the cortical organoids created by researchers at the Yale Stem Cell Center shows the organization of various cell types into layers of tissue. The organoid is 40 days old in this image. The blue dots are cell nuclei; the red patches are progenitor cells for neurons; the green patches are differentiated neurons.

Courtesy of Yangfei Xiang

Deliverance from those problems may have arrived with recent results from three groups. They point toward the possibility of an almost modular approach to building mini-brains, which involves growing relatively simple organoids representative of different developing brain regions and then allowing them to connect with one another.

The most recent of those results was announced two weeks ago in Cell Stem Cell by a group based at the Yale Stem Cell Center. In the first stage of their experiments, they used human pluripotent stem cells (some derived from blood, others from embryos) to create separate organoid replicas of the cortex and MGE. The researchers then let mixed pairs of the ball-shaped organoids grow side by side. Over several weeks, the pairs of organoids fused. Most important, the Yale team saw that, in keeping with proper brain development, inhibitory interneurons from the MGE organoid migrated into the cortical organoid mass and began to integrate themselves into the neural networks there, exactly as they do in the developing fetal brain.

Earlier this year, teams from the Stanford University School of Medicine and the Austrian Academy of Sciences published reports on similar experiments in which they too developed cortical and MGE organoids and then fused them. The three studies differ significantly in their detailssuch as how the researchers coaxed stem cells to become organoids, how they nurtured the growing organoids, and what tests they ran on the derived cells. But they all found that the fused organoids yielded neural networks with a lifelike mix of excitatory neurons, inhibitory neurons and supporting cells, and that they could be developed more reliably than the older types of mini-brain organoids.

To Kriegstein, all three experiments beautifully illustrate that the cells in organoids will readily transform into mature, healthy tissue if given the opportunity. Once you coax the tissue down a particular developmental trajectory, it actually manages to get there very well on its own with minimal instruction, he said. He believes that specialized organoids could bring a new level of experimental control to neuroscientists explorations: Scientists could probe different brain organoids for information about development within subregions of the brain and then use that combined or fused platform to study how these cells interact once they start migrating and encountering each other.

In-Hyun Park , an associate professor of genetics who led the Yale study, is hopeful that organoids might already be useful in preliminary investigations of the developmental roots of certain neuropsychiatric conditions, such as autism and schizophrenia. Evidence suggests that in these conditions, Park said, there seems to be an imbalance between excitatory and inhibitory neural activity. So those diseases can be studied using the current model that weve developed.

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Kriegstein cautions, however, that no one should rush to find clinical significance in organoid experiments. What we really lack is a gold standard of human brain development to calibrate how well these organoids are mimicking the normal condition, he said.

Whatever applications organoid research may eventually find, the essential next steps will consist of learning how to produce organoids that are even more true to life, according to Park. He has also not given up hope that it will eventually be possible to create a mini-brain in the laboratory that is a more complete and accurate stand-in for what grows in our head. Maybe doing so will involve a more complex fusion of organoid subunits, or maybe it will demand a more sophisticated use of growth media and chemicals for directing the organoid through its embryonic stages. There should be an approach to generating a human brain organoid that is composed of forebrain plus midbrain plus hindbrain all together, Park said.

Jordana Cepelewicz contributed reporting to this article.

Original story reprinted with permission from Quanta Magazine , an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

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