Scientists Assemble Frog Stem Cells Into First ‘Living Machines’ – Smithsonian.com

In Michael Levins laboratory at Tufts University, cells can expect to find themselves in unusual company.

Here, the precursors of frog skin sidle up to cells that, in another life, might have helped an amphibians heart beat. Theyre perfect strangers: biological entities that, up until this point, had no business being together. And yet, Levin and his colleagues have found that skin cells and heart cells can be coaxed into coalescing. Placed side by side, they will self-organize into intricate, three-dimensional mosaics of frog cells that arent actually frogs.

Designed by a computer algorithm and surgically shaped by human hands, these skin-heart hybrids, each roughly the size of a grain of sand, dont resemble anything found in nature. But the tasks they accomplish are eerily familiar: Without any external input, they can zoom around Petri dishes, push microscopic objects to and fro, and even stitch themselves back together after being cut.

Levin calls these clusters of cells a new form of lifeone thats not quite an organism and not quite a machine, but perhaps somewhere in between. Named xenobots in honor of the Xenopus laevis African clawed frogs from which their cells derive, they have enormous potential to reveal the rules that govern how the building blocks of life assemble.

With a lot of additional tinkering, xenobot technology could also someday be harnessed to deliver drugs, collect environmental contaminants, and more, Levin and his colleagues write today in Proceedings of National Academy of Sciences. Unlike traditional robots, they argue, the living, self-healing xenobots of the future could theoretically accomplish these feats without polluting the planetand repair themselves to boot.

As plastics and other difficult-to-degrade polymers continue to accumulate in the environment, the incredibly innovative approach offered by the xenobots could be really important for sustainability, says Tara Deans, a biomedical engineer and synthetic biologist at the University of Utah who wasnt involved in the study.

But xenobots also raise a bevy of ethical questions. If things go awry, humans may need protection against these and other forms of artificial lifeor, perhaps, vice versa. When youre creating life, you dont have a good sense of what direction its going to take, says Nita Farahany, who studies the ethical ramifications of new technologies at Duke University and was not involved in the study. Any time we try to harness life [we should] recognize its potential to go really poorly.

In the past several decades, humankind has made staggering advances in robotics. Machines can now master difficult board games, and navigate tough terrain; they can steer themselves as autonomous vehicles, and search for survivors in the wake of disaster. But many of the basic functions that living things accomplish still flummox devices built by human hands. Even in their most creative configurations, metals and plastics simply cant live up to cells.

Biological systems are kind of the envy of all robotics, Levin says. Theyre adaptable, theyre flexible, they self-repair. We dont have robots that can do that. So Levin and his colleagues decided to try and build one that could.

Teaming up with roboticists Sam Kriegman and Josh Bongard at the University of Vermont, Levin and Douglas Blackiston, also at Tufts, asked a computer algorithm to design a series of living machines, using only a few hundred or thousand frog skin or frog heart cells as raw ingredients. The algorithm was instructed to optimize each xenobot for a different basic function, like moving back and forth or manipulating objects.

Its pretty much a hands-off method, Bongard says. We tell the algorithm what we want xenobot to do, but we dont tell it how the xenobot should do it. So the algorithm can explore this infinite space of form and function.

After cycling through multiple configurations, the algorithm would spit out the digital blueprints it believed were best suited to the task at hand. The researchers would then attempt to recreate these designs in Levins lab.

Even after being scraped out of frog embryos and shaken apart in a fluid-filled dish, skin and heart cells will eagerly glom together, aggregating into amorphous clumps thousands of units thick. The cells like to be with each other, Levin says. Next, Blackiston, the teams resident microsurgeon, would take the nascent bots and sculpt them into shapes specified by the computer.

All the xenobots ingredients were bona fide frog. But there was nothing amphibian about the final forms they took. A few were crafted into two-lobed blobs, while others took the forms of hollow, prism-like structures. The bots lacked limbs, skeletons and nervous systems. But they handily tackled the tasks theyd been designed to do.

Tailored to maximize movement, some scooted along the bottom of a Petri dish like microscopic inchworms, powered solely by the contractions of the heart cells studding their interiors. Others, built to transport bits of particulate matter, herded their cargo like sheepdogs, while more still carried it in vacant pouches carved into their custom-made bodies. In some cases, xenobots even interacted, colliding and orbiting each other before eventually coming back apart.

The teams approach, which relies on a mashup of computational and biological techniques, resembles other technologies that have rejiggered the known building blocks of life, says Deans. But rather than tweaking a known template like DNA, the teams techniquewhich simply rearranges existing cells into new configurationsfeels more organic, she says. This process has a resounding respect for the biology thats involved.

At just a millimeter or so across, the xenobots arent capable of much yet. Devoid of mouths or digestive systems, theyre fueled exclusively by the bits of embryonic yolk they came with, and die after about a week when that juice runs dry, Bongard says. But he and his colleagues think the bots could someday be used to deliver drugs into human bodies, or scrape plaque out of arteries. Released into the environment, they could quantify toxins, or sweep microplastics out of oceans.

The team is already experimenting with different sorts of cells, tasked with new types of chores. In a haunting echo of their particle-herding behavior, their xenobots also seem capable of making new versions of themselves, corralling single cells together until they start to coalesce, Levin says. Theyre also resilient: When sliced open, the bots simply repair their wounds and carry on.

While a lot of good could come out of this technology, its also important to consider potential downsides, says Susan Anderson, a philosopher and machine ethics expert at the University of Connecticut who wasnt involved in the study. In the wrong hands, the power of xenobots could easily be exploited as a bioweapon, ferrying poisons instead of medicines into people. Theres also cultural acceptance to consider: The mere idea of reassembling existing life forms could be troubling to some, evoking thoughts of Frankensteins monster or the experimental vivisection in H.G. Wells 1896 science fiction novel The Island of Doctor Moreau.

Humans have certainly tinkered with the recipes of life before. In recent years, bioengineers have reprogrammed cells to churn out life-saving drugs, stripped genomes down to their most minimal states, and cobbled together amalgamations of cells from one animal that resemble the final form of another. But bespoke forms of multicellular life, synthesized from scratch, are still few and far betweenin part because much of biological development remains a black box: Researchers still arent sure, for instance, how tissues, organs and appendages manifest out of single cells.

Studying xenobots could certainly help crack that developmental code. But to get there, scientists will first have to experiment with techniques and technologies they dont fully understand, from the machine learning algorithm that designs these life forms to the cells that spontaneously comprise them, Anderson says.

What the team has presented so far is an early advance, and there are no guarantees about what will emerge from the research, Farahany says. But for this kind of work, its going to be integral to think about what the appropriate ethical frameworks and safeguards would be, she adds. When you have something living, you need fail-safe measures, and you need to know that you can pull the plug.

Bongard and his colleagues acknowledge the gravity of their work. The ethics around this are non-trivial, he says. Though the team hasnt yet brought bioethicists into their research, its something well need to do in the discussion of what to do with this technology, he adds. First, though, we just wanted to demonstrate that this was possible.

View post:
Scientists Assemble Frog Stem Cells Into First 'Living Machines' - Smithsonian.com

News Briefing: Britain and Ireland – The Tablet

Uighur rights activists stage a protest against China's policy in the region, outside the Chinese Embassy in London on Jan 5. Photo: David Cliff/NurPhoto/PA Images

Archbishop of Westminster Cardinal Vincent Nichols used his New Year message to condemn the shameful anti-Semitic graffiti that was daubed across shops, cafes and a synagogue in London at the end of 2019. Its appearance on 29 December in Hampstead and Belsize Park, north London, coincided with the Jewish religious festival of Hanukkah. Cardinal Nichols asked Catholics to include building up the kingdom of God among their New Year resolutions. He proposed that each of us, every person in our society, will shun all form and expressions of hatred against others. He said the anti-Semitic graffiti brings shame to us all and felt that only when we see the good in each other will every person feel welcomed and unafraid.

A parish in the Diocese of Meath, Ireland, has been forced to apologise for a Facebook post that described in vitro fertilisation as incompatible with Catholicism. On Christmas Eve the Parish of the Assumption in Tullamore posted a piece on IVF that said the process damages embryonic stem cells and thus life and is therefore completely, clearly and totally incompatible with our Catholic faith. Health Minister Simon Harris, who recently announced 2 million in funding for fertility/IVF treatment, said he could not understand how any Christian would find IVF objectionable. The post has since been removed by Tullamore parish and a statement published acknowledging that it caused great distress. For hurt caused we apologise. Matters concerning fertility are sacred and sensitive, and all children are cherished and God-given, this is the essence of the Christmas message, the statement said.

Peace groups in Britain have called for restraint in the aftermath of the US airstrike in Baghdad, Iraq, that killed Iranian General Soleimani. President Trumps justification for the killing of Suleimani demonstrates his outdated belief in the myth that the next act of violence will fix something, said Theresa Alessandro, Director of Pax Christi UK. Many are now calling for, and hoping for, restraint, she told The Tablet. Pax Christi UK would like to see clear leadership from our government, demonstrating in words and actions an awareness that killing people does not resolve conflict and a commitment to dialogue and creative, nonviolent ways forward in our relationships with other countries."

Theologian and environmentalist Dr Edward P Echlin died on 23 December at the age of 89. A prolific writer and speaker, and champion of the Christian environmental movement in Britain, Echlin was born in Michigan in the United States and was ordained as a Jesuit. When he left the Jesuits, marrying Barbara, his wife of 45 years, he settled in Britain and focused his work on relating Christianity and the environment. He was Chair Emeritus of Catholic Concern for Animals, and provided theological underpinning for Christian Ecology Link, now Green Christian. His funeral is due to take place at 12.30pm on Wednesday 15 January at St Marthas RC Church in Bexhill.

More than 1,500 people have signed an on-line petition opposing the closure of a Catholic parish in Kent, that was announced to parishioners five days before Christmas. Parishioner Stephanie Boden set up the petition as soon as the community of St Thomas Mores parish in West Malling received a letter from Archbishop John Wilson of Southwark Archdiocese, informing them that their church and the surrounding buildings are going to be put up for sale in Spring 2020. She described the church as the hub of a thriving local Catholic community. Parish Priest Fr Peter Soper, in the parish for two decades, described the news as a devastating blow. Bishop Wilson said that structural problems with other buildings on the site would be too costly to repair.

Million Minutes, a Catholic youth charity, is recruiting its first paid chief executive. Until now the role, held by founder Danny Curtin for nine years, has been voluntary, but with the paid appointment the charity hopes to expand and develop in order to grow the work it does with young people.

Read this article:
News Briefing: Britain and Ireland - The Tablet

The Slow March Toward the First Same-Sex Couple to Have a Baby – Discover Magazine

Cara Gormallys pregnancy was shadowed by grief. As a queer woman wanting to have a baby, the biology professor had figured finding a sperm donor would be the only obstacle she and her partner faced. But thanks to Gormallys organizational skills and love of making lists, the couple landed on a donor with relative ease.

Then, Gormally struggled to conceive. Each month brought fresh disappointment and loss.

So much of the process depended on random, heart-breaking chance, she says. The emotional and financial roller coaster was exhausting.

But it wasnt the hardest part. The couple had accepted that, as much as they wanted a baby, their child wouldnt be biologically related to Gormallys spouse.

I grieved that our child wouldnt be genetically related to both of us, Gormally says. I longed for the biologically impossible.

But now, a new set of technologies have the potential to change whats possible allowing same-sex partners to have kids who share their genetic material, just like straight couples.

In mammals, pretty much every cell in the body carries two sets of genetic material. One set comes from mom and the other from dad. Eggs and sperm are the only exceptions; they have just one set. Then, when a sperm fertilizes an egg, those two sets combine, restoring the usual number to two sets per cell.

Gormally and other same-sex partners are currently barred from their dreams by a phenomenon called genomic imprinting. It uses a distinct tag from each parent to mark the DNA that mammals pass on to their offspring. The process ensures that, for a small percentage of genes, we only express the copy of genetic material provided by our mother or our father. When this imprinting process goes awry, kids can end up with inactive gene regions that cause miscarriages, developmental defects and cancer.

(Credit: Jay Smith/Discover)

During this genomic imprinting, moms distinct collection of tags typically turns off certain genes, so that just dads copy is expressed. And dad imparts his own marks that leave only the maternal copy on. (Most imprints silence gene expression, but some activate it.) Thats a problem for same-sex couples who want to have a baby. If both sets of an offsprings genes come from maternal DNA, for example, then both copies of imprinted genes will be off. So, the embryo cant make any of the genes products.

We dont get the full set of [gene] products that we need to undergo proper development unless we have both a maternal and paternal contribution to a fertilized egg, says Marisa Bartolomei, a geneticist at the University of Pennsylvania in Philadelphia, who discovered one of the first imprinted genes in mice.

Scientists discovered genomic imprinting in mammals about 30 years ago. During experiments in the mid-1980s, researchers removed either the maternal or paternal genetic contributions from newly fertilized mouse eggs. Then, they transferred in a second set of genes from another mouse to create embryos with either two sets of female genetic material or two sets of male genetic material. A surrogate mouse was able to gestate the embryos, but none survived. The finding showed normal development requires genetic material from both a father and the mother. More than that, the outcomes revealed that maternal and paternal genetic material differ from each other in meaningful ways.

Later experiments revealed mice developed differently depending on whether they happened to receive both copies of certain regions of DNA from one parent (rather than one copy from each parent).

Mice with hairpin-shaped tails were telling examples. When researchers deleted the gene region responsible for a hairpin tail from a mothers genome, mice embryos grew large and died partway through gestation. In contrast, deleting the same region from the paternal genome had no effect on the rodents growth or development.

In the three decades since, researchers have found more imprinted genes (they suspect there are between 100 and 200 such genes) and the molecular tags that silence them. Scientists have also taken strides connecting imprinting defects to developmental disorders in humans. But all along, researchers have known that imprinting prevents same-sex parents from having children.

In October 2018, researchers overcame this impossibility in mice. By deleting imprinted regions, Wei Li and a team at the Chinese Academy of Sciences in Beijing produced healthy mice from two moms. The researchers also created mouse pups from two dads for the first time. However, the offspring died just a few days after birth.

Despite the loss, Li is optimistic. This research shows us what is possible, he says.

To overcome the imprinting barrier, Li and his fellow researchers turned to CRISPR, a gene-editing technique thats made altering genomes easier than ever. They used the tool to delete gene regions from embryonic stem cells from mice mothers. The researchers then injected these modified stem cells into the egg of a female mouse and then used a third surrogate female mouse to carry the fetus to term.

The team had already seen some success two years earlier when they created mouse pups with two genetic mothers by deleting two imprinted regions. Although these bimaternal mice also grew to adulthood and produced pups of their own, they developed growth defects. On average, the bimaternal mice were 20 percent lighter than their hetero-parental counterparts. In their latest study, Li and his team also deleted a third region from the mothers genes, which restored the animals growth to normal.

But the scientists had to clear a few more hurdles to generate mice with two genetic fathers. They found, through a process of trial and error, that they needed to remove twice as many imprinted regions in the bipaternal mice as the bimaternal mice. In total, the team deleted seven imprinted regions to successfully create mice from two dads.

Still, the numbers were not in their favor. Only two and a half percent of embryos made it to term and less than half of one percent lived for two days. None made it to adulthood.

The produced bipaternal mice are not viable, which implies more obstacles are needed to cross to support their postnatal survival, if possible, Li says. The lower birth rate, on the other hand, implies the existence of an unknown barrier hindering the development of bipaternal embryos.

In contrast, the bimaternal mice fared much better. These mice grew to adulthood and were healthy enough to have pups of their own by mating with typical male mice. They also behaved the same as the control mice. As far as the researchers could tell, the bimaternal mice appear as healthy and normal as any other laboratory mice.

It does not mean that they are normal in every aspect, Li cautions. One cannot investigate all the aspects under restricted experimental conditions with a limited number of animals.

Despite the researchers success, Li says the technique is not ready for use in humans. It is never too much to emphasize the risks and the importance of safety before any human experiment, he says, particularly in regard to the bipaternal offspring, which currently are severely abnormal and cannot survive to adulthood.

The bimaternal offspring hold more promise. The team is now working to translate their findings to monkeys. And that work could bring the impossible one step closer to feasible for humans.

Lis research is encouraging but its a long way from helping Gormally and her spouse. However, its also not the only shot for same-sex couples. Another new technology called in vitro gametogenesis, or IVG, may be an alternative potential path for same-sex couples to have their own kids.

Scientists use the technique to make eggs and sperm from other cells in the body. To do so, biologists first reprogram adult skin cells to become stem cells. Then, they stimulate the skin-derived stem cells to develop into eggs or sperm.

Researchers from Japan have now perfected the technique in mice. And in groundbreaking work, Katsuhiko Hayashi and Mitinori Saitou and their team generated functional eggs from mice tail cells.

The researchers then fertilized the eggs with sperm from male mice and implanted the embryos into surrogate mothers. The offspring grew up healthy and fertile. In principle, this approach could allow a womans skin cells to be engineered into sperm and used to fertilize her partners egg.

IVG could transform same-sex couples ability to have their own children. If it had been possible at the time, we definitely wouldve have tried to do it, says Gormally, who is now a proud parent to a toddler thanks to her and her spouses sperm donor. [Its] a total game-changer.

This story is part of "The Future of Fertility" a new series on Discover exploring the frontiers of reproduction.

Read more:

Can Humans Have Babies in Space?

George Church Wants to Make Genetic Matchmaking a Reality

Human Gene Editing is Controversial. Shoukhrat Mitalipov Isn't Deterred

More:
The Slow March Toward the First Same-Sex Couple to Have a Baby - Discover Magazine

Ethics of gene editing must be decided by each one of us – Mail and Guardian

COMMENT

Gene editing is an exciting area of scientific research. It allows scientist to use gene-editing tools, such as CRISPR, to alter the genetic sequence of an organisms cells, with a specific result in mind.This creates the potential to alter crops so that they are more nutritious, or alter a human beings genetic makeup to remove the potential of an individual to develop a particular disease. The latter has proved controversial, as this new ability that gene editing gives us to alter our genetic characteristics is unprecedented, and many regulatory frameworks do not specifically refer to gene editing and CRISPR.

With respect to the gene editing of a human, there is distinction between somatic gene editing, which will alter specific cells only in an existing person, and germline editing, which is gene editing performed on human eggs, sperm, or embryos. This is the area of heated debate, because while somatic gene editing will only affect a particular patient, germline editing will alter an embryos DNA in a manner which is heritable.

In this way, germline editing creates the potential of altering the genetic heritage of future people, an idea which ethicists, philosophers, lawmakers, scientists and others are not comfortable with. For this reason, while there are some somatic gene editing trials under way, there has been consensus that germline editing should not be done until the safety of gene editing has been demonstrated, and the ethical issues can be debated.

In November 2018, the Chinese scientist, He Jiankui, revealed to the world that he had successfully gene-edited human embryos. He spoke of his technological feat at the Second International Summit on Genome Editing in Hong Kong, where he presented his method of gene editing human embryos to attempt to create children who would be resistant to HIV infection. The research presented appeared to show that he had successfully gene-edited the human embryos, which were then implanted into a woman and carried to term.

The resulting children, twin girls referred to only by their pseudonyms Lulu and Nana appeared to be healthy and resistant to HIV infection. The gene editing was a success. But the news was met with international outcry, and calls for a moratorium to debate the issues inherent in the gene editing of human beings. Until this time, there had been no clinical application of gene editing to human embryos, because this is largely prohibited by ethics and legal guidelines around the world. He appeared to have had all of his paperwork in order ethical approval from his research institution to conduct the procedure and informed consent from couples willing to have their embryos genetically edited. But, according to the Human Embryonic Stem Cell Research Ethics Guiding Principles issued by Chinas ministry of science and technology and the ministry of health in 2003, human blastocysts that have been used for research cannot be implanted into the reproductive system of humans or any other animal. The genetic manipulation of human gametes, zygotes, and embryos for the purpose of reproduction is also prohibited.

So how did this failure of regulatory oversight happen? Whispers of He being placed under house arrest began to circulate. But what would ultimately happen to He, who had clearly broken the rules?

On December 30, a year after his revelation to the gene-editing summit, the world found out. He, together with two co-defendants, were sentenced in the Nanshan district peoples court in Shenzhen for the illegal practice of medicine. Immediately upon release of the news of the birth of the gene edited children in 2018, the Guangdong province immediately set up a gene editing baby incident investigation team. On July 31 last year, a public prosecution notice was filed in the Nanshan district peoples court. To protect the privacy of the individuals involved in the case, the court heard the case in private on December 27. The court held that the behaviour of He, together with Zhang Renli and Qin Jinzhou, embryologists who had worked with him, constituted the crime of illegal medical practice. He was sentenced to three years imprisonment and fined three million yuan, Zhang was sentenced to two years imprisonment and fined one million yuan and Qin was sentenced to one year and six months imprisonment and two years probation. The finding of the court was that the defendants had practiced medicine illegally, under the guise of scientific research and innovation.

The details which have now come to light are arguably more shocking than the news of the birth of the children in 2018.

The court learnt that in 2016, in order to realise his goal of being the first scientist to create the worlds first gene-edited baby, He had formulated a business plan for gene-edited babies and raised funds. In 2017, the defendants arranged for six couples to impersonate people awaiting ordinary assisted reproductive help. He later instructed Zhang and others to falsify the medical ethics approval that would be necessary to conduct the gene editing procedure. He also arranged for necessary reagent materials, which are prohibited for human diagnosis and treatment, to be purchased from outside the country. In August 2017, instructed by He, Zhang began injecting the gene-editing reagents into the fertilized eggs of six couples in violation of the Chinese regulations, and then took samples of the cultured blastocysts (early embryos) for inspection. He selected blastocysts and Zhang transplanted them into patients through an unsuspecting doctor. The result was that two women became pregnant. In 2018, one patient gave birth to twin baby girls, and in 2019, a second patient gave birth to a baby girl. The court also learnt that between May and June 2018, He and Qin had arranged for two more couples to travel to Thailand where he attempted to conduct the gene-editing and implantation procedure again. No pregnancies resulted from this endeavour.

The court held that the defendants had deliberately violated the rules to chase personal fame and fortune, and had opted deceptive and counterfeiting methods to maliciously evade the supervision of the national competent authority, and applied gene editing technology to assisted reproductive medicine.

The evidence also showed that when He obtained consent from the couples who underwent the procedure, he had described the technology as mature, safe and as having no risk. From a legal perspective, the consent of these patients was not informed as they had been given false information. The behaviour of the defendants, from the procuring of reagents, counselling of couples, screening and injecting of eggs, implantation and the resulting births also violated the boundaries of scientific experiments and should instead be regarded as medical behaviours. None of the defendants were licenced physicians and yet were still carrying out medical activities, which amount to the crime of illegal medical practice.

Will this judgment impede innovation in gene editing? It may not necessarily do so. This case will instead help to define the boundaries between what is legal and illegal, at least in China. What will follow now, is stricter oversight and more deliberation on the issues inherent in gene editing. China has already enacted several revisions to its existing laws. More countries will follow. The difficulty with developing a framework is that it will boil down to asking the difficult question: Who should decide what may be allowed and what should be prohibited? The prevailing opinion is that since gene editing will affect all of us, because it involves genetic manipulation of the human race, we should all be part of the conversation about its regulation.

Although this is a useful starting point, we must be mindful of cultural and other societal barriers. If the question being debated is what genetic conditions may be edited out of the human population, we must bear in mind that the answer will differ depending on the society to which we pose that question. A recent example is that of the Russian scientist, Denis Rebrikov, who in 2019 announced his intention to genetically edit human embryos to remove the genetic predisposition for deafness. If we are asked to consider whether deafness is a disease or disability, we may receive conflicting opinions.

The knee-jerk response to Rebrikovs announcement was that deafness is not a disease, not a disability, and that there is a societal structure to assist hearing impaired persons. Further, deafness has assimilated into culture, and to allow gene editing of embryos in a manner which results in deafness being removed from the human population does not speak well to the proponents view of persons who are hearing impaired. But Rebrikov has offered an argument in favour of gene editing deafness out of the population. In Russia, deafness is often associated with societal stigmatisation, and the hearing impaired do not necessarily enjoy the support mechanisms of those living in other countries.

This is just one example of one genetic condition, with a set of ethical issues attached to it. A debate on germline gene editing will require us to debate the ethical issues in relation to any disease or genetic condition to which gene editing may be applied.

Asking these questions in different societies, each with values and traditional, religious or cultural norms that may differ is going to create difficulties. Our DNA makes us similar, our traditions and cultures make us different. The regulation of gene editing is going to ask that we find a constructive way to harmonise the two. Lulu and Nana were the worlds first gene-edited babies. More will be born, but by that time the regulatory mechanisms will undoubtedly have changed.

Sheetal Soni is at the School of Law at the University of KwaZulu-Natal

Here is the original post:
Ethics of gene editing must be decided by each one of us - Mail and Guardian

Highs and Lows of Stem Cell Therapies: Off- The-Shelf Solutions – P&T Community

NEW YORK, Jan. 7, 2020 /PRNewswire/ --

Report Includes: - An overview of recent advances in stem cell therapies and coverage of potential stem cells used for regenerative advanced therapies

Read the full report: https://www.reportlinker.com/p05835679/?utm_source=PRN

- Discussion on role of genomic and epigenomics manipulations in generating safe and effective treatment options - Identification of autologous and allogeneic cells and their usage in creating advanced therapy medical products (ATMPs) - Information on 3D cell culture and discussion on advances in gene editing and gene programming techniques such as CRIPSR/Cas9, TALEN, and ZINC fingers - Insights into commercial and regulatory landscape, and evaluation of challenges and opportunities for developing autologous and allogenic "off the shelf" solutions

Summary Stem cells are unique in their ability to divide and develop into different cell types that form tissues and organs in the body during development and growth.The stem cell's role is to repair impaired or depleted cells, tissues and organs in the body that are damaged by disease, injury, or normal wear and tear.

Stem cells are found in every organ, but are most abundant in bone marrow, where they help to restore the blood and immune system.

Stem cells may be derived from various sources, including - - Adult stem cells (ASCs): Derived from tissue after birth, these include bone marrow, brain, peripheral blood, skeletal muscle, skin, teeth, heat, gut, liver, ovarian epithelium and testis, as well as umbilical cord stem cells and blood. These cells are currently most widely used for cellbased therapies. Hematopoietic stem cells (HSCs), which are derived from bone marrow, can give rise to red blood cells, white blood cells and platelets, whereas mesenchymal stem cells (MSCs) are derived from the stroma and give rise to non-blood forming cells and tissues. - Human embryonic stem cells (hESCs): Derived from embryos, these include stems cell lines, aborted embryos or from miscarriages, unused in vitro fertilized embryos and cloned embryos. There are currently no clinically approved treatments for embryonic stem cells. - Inducible pluripotent stem cell (iPSCs): These are stem cells generated in the laboratory by reprogramming adult cells that have already differentiated into specific cells, such as liver cells. They are used either for research purposes (e.g., experimental medicine testing toxicity of new drugs) or are under research for potential future clinical use.

Read the full report: https://www.reportlinker.com/p05835679/?utm_source=PRN

About Reportlinker ReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

__________________________ Contact Clare: clare@reportlinker.com US: (339)-368-6001 Intl: +1 339-368-6001

View original content:http://www.prnewswire.com/news-releases/highs-and-lows-of-stem-cell-therapies-off--the-shelf-solutions-300982411.html

SOURCE Reportlinker

Read the original post:
Highs and Lows of Stem Cell Therapies: Off- The-Shelf Solutions - P&T Community

Pune to host fifth edition of global Drosophila conference – The Hindu

The city is set to host the fifth edition of the Asia Pacific Drosophila Research Conference (APDRC5), which is being organised in the country for the first time by the Indian Institute of Science Education and Research (IISER).

This biennial conference, which is to be held between January 6 and 10, aims to promote the interaction of Drosophila researchers in the Asia-Pacific region with their peers in the rest of the world. It will bring together scientists from all over the world who use the fruit fly, Drosophila, as a model organism to address basic and applied questions.

Drosophila is one of the most widely-used and preferred model organisms in biological research across the world for the last 100 years. Several discoveries in biology have been made using this. Its genome is entirely sequenced and there is enormous information available about its biochemistry, physiology and behaviour, said professor (biology) Sutirth Dey of IISER.

The event will feature 430 delegates: 330 Indian and 100 foreign. It will see the participation of two Nobel laureates, professors Eric Wieschaus and Michael Rosbash, known for their seminal contribution to the fields of development biology and chronobiology respectively.

Prof. Wieschaus, an American evolutionary developmental biologist, shared the Nobel in Physiology in 1995 with Edward B. Lewis and Christiane Nsslein-Volhard for his work on genetic control of embryonic development, while Prof. Rosbash shared the Nobel in 2017 in Physiology along with Michael Young and Jeffrey Hall for their discoveries of molecular mechanisms controlling the circadian rhythm.

This event is one of the largest meetings of Drosophila researchers in the whole world and attracts scientists working in diverse disciplines ranging from cell and molecular biology to ecology and evolution, said Prof. Dey.

Explaining the choice by the APDRC board of IISER to organise the meet, he said the institute is one the premier scientific research institutes of the country and is very strong in Drosophila research, given that there are five professors and 30 Ph.D. scholars who were using Drosophila to answer questions in developmental biology.

A total 57 talks and 240 posters on topics ranging from gametogenesis and stem cells, morphogenesis and mechanobiology, hormones and physiology, cellular and behavioural neurobiology, infection and immunity and ecology and evolution are scheduled for the conference.

One of the highlights of this conference is that we are explicitly encouraging undergraduates from various institutes of the world to participate in it. There is a pre-conference symposium called signals from the gut in collaboration with the National Centre for Cell Science, as well as a pre-conference microscopy workshop on super-resolution microscopy. This will feature microscopes from fluorescence imaging to super resolution imaging (50 nm resolution) which are vital for certain kinds of fly work, Prof. Dey said.

The last four editions of this conference took place in Taipei, Seoul, Beijing and Osaka.

You have reached your limit for free articles this month.

Register to The Hindu for free and get unlimited access for 30 days.

Find mobile-friendly version of articles from the day's newspaper in one easy-to-read list.

Enjoy reading as many articles as you wish without any limitations.

A select list of articles that match your interests and tastes.

Move smoothly between articles as our pages load instantly.

A one-stop-shop for seeing the latest updates, and managing your preferences.

We brief you on the latest and most important developments, three times a day.

Not convinced? Know why you should pay for news.

*Our Digital Subscription plans do not currently include the e-paper ,crossword, iPhone, iPad mobile applications and print. Our plans enhance your reading experience.

Read the original here:
Pune to host fifth edition of global Drosophila conference - The Hindu

Human Embryonic Stem Cells | The Embryo Project Encyclopedia

Human Embryonic Stem Cells

Stem cells are undifferentiated cells that are capable of dividing for long periods of time and can give rise to specialized cells under particular conditions. Embryonic stem cells are a particular type of stem cell derived from embryos. According to US National Institutes of Health (NIH), in humans, the term embryo applies to a fertilized egg from the beginning of division up to the end of the eighth week of gestation, when the embryo becomes a fetus. Between fertilization and the eighth week of gestation, the embryo undergoes multiple cell divisions. At the eight-cell stage, roughly the third day of division, all eight cells are considered totipotent, which means the cell has the capability of becoming a fully developed human being. By day four, cells begin to separate and form a spherical layer which eventually becomes the placenta and tissue that support the development of the future fetus. A mass of about thirty cells, called the inner cell mass, forms at one end of the sphere and eventually becomes the body. When the sphere and inner cell mass are fully formed, around day 5, the pre-implantation embryo is referred to as a blastocyst. At this point the cells in the inner cell mass have not yet differentiated, but have the ability to develop into any specialized cell type that makes up the body. This property is known as pluripotency. As of 2009, embryonic stem cells refer to pluripotent cells that are generally derived from the inner cell mass of blastocysts.

In November 1998, two independent publications announced the first successful isolation and culture of pluripotent human stem cells. While working at the Wisconsin National Primate Research Center, located at the University of Wisconsin-Madison, James A. Thomson and his team of researchers cultured human embryonic stem cells from the inner cell mass of donated embryos originally produced for in vitro fertilization. The characteristics of the cultured cells were consistent with previously identified features in animal stem cells. They were capable of long-term self-renewal and thus could remain undifferentiated for long periods of time; they had particular surface markers; and they were able to maintain a normal and stable karyotype. Thomsons team also observed derivatives of all the three germ layersendoderm, mesoderm, and ectoderm. Since the three germ layers precede differentiation into all the cell types in the body, this observation suggested that the cultured cells were pluripotent. The team published Embryonic Stem Cell Lines Derived from Human Blastocysts, in the 6 November Science issue. Soon afterwards, a research team led by John D. Gearhart at the Johns Hopkins School of Medicine, published Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells in Proceedings of the National Academy of Science. The paper detailed the process by which pluripotent stem cells were derived from gonadal ridges and mesenteries extracted from aborted five-to-nine week old human embryos. Gearhart and his team noted the same observations as Thomsons team. Despite coming from different sources, according to NIH, the resultant cells seem to be the same.

The largest source of blastocysts for stem cell research comes from in vitro fertilization (IVF) clinics. Used for reproductive purposes, IVF usually produces an abundance of viable blastocysts. Excess blastocysts are sometimes donated for research purposes after obtaining informed consent from donors. Another potential method for producing embryonic stem cells is somatic cell nuclear transfer (SCNT). This has been successfully done using animal cells. The nucleus of a differentiated adult cell, such as a skin cell, is removed and fused with an enucleated egg, an egg with the nucleus removed. The egg, now containing the genetic material from the skin cell, is believed to be totipotent and eventually develops into a blastocyst. As of mid-2006, attempts to produce human embryonic stem cells using SCNT have been unsuccessful. Nonetheless, scientists continue to pursue this method because of the medical and scientific implications of embryonic stem cells lines with an identical genetic makeup to particular patients. One problem faced in tissue transplants is immune rejection, where the host body attacks the introduced tissue. SCNT would be a way to overcome the incompatibility problem by using the patients own somatic cells.

Recent discoveries in cultivating human embryonic stem cells may potentially lead to major advancements in understanding human embryogenesis and medical treatments. Previously, limitations in access and environmental control have stunted research initiatives aimed at mapping out the developmental process. Insights into differentiation factors may lead to treatments into such areas as birth defects. Manipulation of the differentiation process may then lead to large supplies of stem cells for cell-based therapies on patients with Parkinsons disease, for example. In theory adult stem cells can also be cultivated for such purposes, but isolating and identifying adult stem cells has been difficult and the prospects for treatment are more limited than using embryonic stem cells.

Despite the potential benefits that may come about through human embryonic stem cell research, not everyone in the public embraces it. Several ethical debates surround this newly developing research field. Much of the debate stems from differing opinions on how we should view embryos: is an embryo a person? Should an embryo be considered property? Ethical concerns in embryonic stem cell research include destroying human blastocysts, laws surrounding informed consent, and particularly for SCNT, misapplication of techniques for reproductive cloning. For the latter concern, SCNT does produce a blastocyst which contains stem cell clones of an adult cell, but the desired application is in growing replacement tissues. Still, a portion of the public fears the hypothetical one day, when someone decides to use SCNT to develop and raise a human clone.

The public debate continues, advancing along with the changes in the field. As of 2006, public opinion polls showed that majority of religious and non-religious Americans now support embryonic stem cell research, but opinions remain divided over whether it is legitimate to create or use human blastocysts solely for research.

Wu, Ke, "Human Embryonic Stem Cells".

(2010-09-13). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/2055.

Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia.

Arizona Board of Regents Licensed as Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported (CC BY-NC-SA 3.0) http://creativecommons.org/licenses/by-nc-sa/3.0/

See the article here:
Human Embryonic Stem Cells | The Embryo Project Encyclopedia

Embryonic stem cell | biology | Britannica

Embryonic stem cell | biology | Britannica rn rn rntrn rn"}

biology

THIS IS A DIRECTORY PAGE. Britannica does not currently have an article on this topic.

Alternative Titles:ES cell, ESC

Embryonic stem cells (often referred to as ES cells) are stem cells that are derived from the inner cell mass of a mammalian embryo at a very early stage of development, when it is composed of a hollow sphere of dividing cells

In contrast, embryonic stem cells (ESCs) can be harvested once and cultured indefinitely. Moreover, ESCs are pluripotent, meaning that they can be directed to differentiate into any cell type, which makes them an ideal cell source for regenerative medicine.

condemned medical research using embryonic stem cells, though it endorsed research with adult stem cells. While many theologians, clergy, and laypersons agreed with church policy on these matters, many others disagreed and even chose to defy it.

which point a culture of embryonic stem cells (ESCs) can be created from the inner cell mass of the blastocyst. Mouse, monkey, and human ESCs have been made using SCNT; human ESCs have potential applications in both medicine and research.

Evans and a colleague discovered embryonic stem cells (often referred to as ES cells) in mice. These stem cells are derived from the inner cell mass of a mammalian embryo at a very early stage of development. After determining that ES cells could serve as vehicles for the transmission of

in the late 1980s with embryonic stem cells. Wilmut and his colleagues were interested primarily in nuclear transfer, a technique first conceived in 1928 by German embryologist Hans Spemann. Nuclear transfer involves the introduction of the nucleus from a cell into an enucleated egg cell (an egg cell that has

Your preference has been recorded

Here is the original post:
Embryonic stem cell | biology | Britannica

Embryonic Stem Cell | California’s Stem Cell Agency

Diabetes mellitus currently afflicts approximately 370 million people worldwide, with projections of over 550 million by the year 2030 (sources: World Health Organization; International Diabetes Federation). In the year 2000 there were approximately 2 million cases of diabetes in California (source: Diabetes Control Program, California Department of Health Services). Further, the disease disproportionately affects certain minority groups and the elderly. Despite the use of insulin and advances in its delivery, the human cost of diabetes is underscored by the financial costs to society: tens of billions of dollars each year in California alone. The primary cause of type 1 diabetes, and contributing significantly to type 2 diabetes as well, is the loss of insulin-producing pancreatic beta cells. The CIRM Diabetes Disease Team Project is developing an innovative beta cell replacement therapy for insulin-requiring diabetes. If successful, the therapy will go beyond insulin function, and will perform the full array of normal beta cell functions, including responding in a more physiological manner than manual or mechanized insulin self-administration. Because they will be more physiological, the replacement cells could reduce the long-term effects of diabetes. Moreover, the cell therapy will alleviate patients of the constant monitoring of blood glucose, painful insulin injections, and the ever-present risk of overdosing with insulin. For these reasons, it is possible that the product could transform the diabetes treatment landscape dramatically and even replace pharmaceutical insulin in the market. This product will be available in California first, through clinical testing, and if approved by the FDA for commercial production, will eventually help hundreds of thousands of Californians with diabetes. The product will substantially increase quality of life for patients and their families, while significantly reducing the health care burden in the state. The proposed project will employ Californian doctors and scientists, and success will prove highly noteworthy for the state. Lastly, once commercially marketed, the product will yield additional jobs in manufacturing, sales, and related industries, and generate revenue for California. Given the market need and the clear feasibility, the product could become the most significant stem cell-based medical treatment of the coming decade, and that will be a tremendous achievement for California, its taxpayers, and CIRM.

Link:
Embryonic Stem Cell | California's Stem Cell Agency

Making blood on demand: How far have we come? – Science Codex

The reconstitution of the blood system in humans holds great therapeutic potential to treat many disorders, like blood cancers, sickle-cell anemia and others. Successful reconstitution requires the transplantation and engraftment of hematopoietic (or blood) stem cells (HSCs), which after reaching their niche, start producing all types of blood cells, including platelets, white and red blood cells.

In current clinical practice, this is carried out by infusing HSCs obtained from a matched donor who is immunologically compatible with the patient in need (allogeneic transplantation), or by the expansion of the patient's own HSCs in the lab, and then re-infusing them back into the patient (ex-vivo, autologous transplantation). However, the utility of both routes is currently limited by a number of factors. First, in the case of allogeneic transplantation, the scarcity of matched donors significantly increases the waiting time, which could be detrimental to the patient. Second, the ex vivo expansion of HSCs, whether allogeneic or autologous, has been a challenging task, due to the limited proliferative potential these cells exhibit in culture. These limitations have raised the need for other sources of HSCs that would alleviate the need for matched donors and yield functional HSCs in large quantities.

In 2007, Professor Shinya Yamanaka and colleagues demonstrated that somatic cells, like skin fibroblasts, could be reprogrammed back to a cellular state that resembled human embryonic stem cells (hESCs), which are a group of cells found in the blastocyst-stage human embryo and contribute solely to the development of the human fetus during pregnancy. The reprogrammed cells were termed, Induced Pluripotent Stem Cells (iPSCs). In addition to their developmental potential, human ESCs and iPS cells display unlimited proliferative potential in culture, which makes them an ideal source of cells for regenerative medicine in general and for hematopoietic differentiation to obtain possibly unlimited quantities of HSCs. Therefore, there has been a growing interest to harness the potential of these cells for treating blood disorders.

However, advancement in deriving functional HSCs from human pluripotent stem cells has been slow. This has been attributed to incomplete understanding of the molecular mechanisms underlying normal hematopoiesis. In this review, the authors discuss the latest efforts to generate HSCs capable of long-term engraftment and reconstitution of the blood system from human pluripotent stem cells. Stem cell research has witnessed milestone achievements in this area in the last couple of years, the significance of which are discussed and analyzed in detail.

The authors additionally discuss two highly important families of transcription factors in the context of hematopoiesis and hematopoietic differentiation, the Homeobox (HOX) and GATA proteins. These are thought of as master regulators, in the sense of having numerous transcriptional targets, which upon activation, could elicit significant changes in cell identity. The authors hypothesize that precise temporal control of the levels of certain members of these families during hematopoietic differentiation could yield functional HSCs capable of long-term engraftment.

The authors conclude the review with a summary of future perspectives, in which they discuss how newly developed techniques, like the deactivated-Cas9 (dCas9) gene-expression control system, can be utilized during the course of hematopoietic differentiation of pluripotent stem cells for precise temporal control of the aforementioned master regulators to achieve functional HSCs.

Read this article:
Making blood on demand: How far have we come? - Science Codex