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Scientists creating synthetic human brains, lungs, livers, heart and limbs to obviate the need of transplants and enhance quality of life

In the UK, there are some 7,000 people on the list who are in dire need of organ transplants and In the US, the number awaiting transplant is around 120,000, with 20 dying each day for want of an organ. Current organ transplant patients have to take immunosuppressant drugs all their life to prevent the body rejecting the new addition whereas using human cells, specifically those from the same patient, would reduce any possibility of rejection. In near term it is also being used to assess the drug safety and efficacy and disease research.

 

Several labs around the world, are working on the futuristic idea of growing custom-made organs in the lab that will allow creating a more permanent solution for patients. By offering a true replacement by grafting cells from the patient’s own body onto a “base material”, would also remove the major problem of rejection, which must be suppressed with immunosuppressants. If synthetic organs become a reality, they will not only obviate the need of transplants, but they would enhance the quality of life for our ageing population, and allow us to live centenarian lives while being fit and healthy.

 

The scientists are working on developing organs in the laboratory that has given hope of transplanting complex organs like kidneys, pancreases and lungs for amputees in a decade or so. SCIENTISTS in China are extremely close to being able to controversially grow human organs in pigs so they can be transplanted to ill patients. Pigs are an ideal candidate to help as their organs, specifically the heart and kidneys, are very similar to that of a humans. Recent experiments in China have shown monkeys can survive for an extended period of time with organ transplants from pigs.

 

Zhao Zijian, director of the Metabolic Disease Research Centre at Nanjing Medical University in Jiangsu, told South China Morning Post: “We have patients dying from organ failure and their desperate relatives pleading for them to have the chance to live. China is also home to the largest pig cloning factory in the world – BGI – which produces up to 500 cloned piglets annually. Scientists believe this is the perfect set up – the cloners grow the pigs and the doctors add human organs. One researcher from BGI said: “This is unmatched by any other country. The world will eventually depend on China for organs.”

 

In a major landmark for bioengineering, lungs that were made in the lab have been successfully implanted into pigs for the first time, enabling them to breathe normally. They have not yet been hooked up to a crucial artery, but the team behind the work are hopeful. “I would argue this is the first time that a tissue-engineered organ has been implanted in a large animal and shown to survive and have any degree of function whatsoever.” In 2014, Nichols’ team became the first to bioengineer a human lung. A year later, the researchers implanted a single lab-built lung into a pig—another first.  They’ve grown three more pig lungs since, using cells from their intended recipients, and transplanted each of them successfully without the use of immunosuppressive drugs.

 

Scientists have managed to grow perfect human blood vessels as organoids in a petri dish for the first time. The breakthrough engineering technology, outlined in a new study published in Nature in Jan 2019, dramatically advances research of vascular diseases like diabetes, identifying a key pathway to potentially prevent changes to blood vessels — a major cause of death and morbidity among those with diabetes.

 

Recently artificial organs are being tried using 3D printing or bioprinting. The first human corneas to come out of a low-cost 3D printer were created by a team of researchers at Newcastle University in the UK.

 

“I think within ten years we won’t see any more heart transplants, except for people with congenital heart damage, where only a new heart will do,” Stephen Westaby, from the John Radcliffe Hospital in Oxford, told The Telegraph.

 

Synthetic Organs

The first technique that has been used by Scientists for developing artificial organs is stem cells. In 2013, a  team from Japan, Yokohama City University’s graduate school of medicine,  became first to grow liver cells from skin stem cells in a petri dish and then transplanted them successfully into mice. Since then, scientists have been able to grow artificial versions of complex tissues, including entire limbs, Heart tissue, windpipes, mini brains and bladders , all from stem cells.

 

Stem cells are a class of  undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources: Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development and Adult  stem cells  that  are found inside of different types of tissue such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver.  Both embryonic stem cells and IPS cells have the ability to turn into any part of the body. However, using embryonic stem cells is very controversial because it results in destruction of embryo itself.

 

Science has also made it possible to produce artificial organs using another technological marvel, 3D printing. When applied to medicine, the technique is referred to as 3D bioprinting — and the achievements in the emerging technique have already been quite remarkable.

 

Thus far, scientists have successfully 3D-bioprinted several organs, including a thyroid gland, a tibia replacement that’s already been implanted into a patient, as well as a patch of heart cells that actually beat. All of these organs were made possible by refinements to the type of bioink.

 

Bioengineers have developed a 3D bioprinting technique that works with natural materials and is easy to use, allowing researchers of varying levels of technical expertise to create lifelike tissues, such as blood vessels and a vascularized gut. The goal is to make human organ models that can be studied outside the body or used to test new drugs ex vivo.

 

Miniature brain

In 2013, scientists from the Institute of Molecular Biotechnology in Vienna, Austria announced they had successfully created a miniature brain in the lab. Using stem cells, they grew a model of a developing brain that was about the size of an embryonic human brain at nine weeks old. The cerebral organoid didn’t look exactly like a real brain, but it had active neurons and had much the same organizational structure. Researchers used human embryonic stem cells and induced pluripotent stem cells (IPS cells) for this research. IPS are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes.

 

Now  scientists are creating the three-dimensional organoids from human stem cells  comprising functional neurons, distinct layers of cortex, and other architecture that mimics the full-sized version. In January, Salk Institute researchers developed human-pig chimeras, creating the possibility that pigs with human brain cells might also develop human consciousness.

 

George Church’s lab at Harvard says it has been able to give the organoids a blood supply. “Vascularization” could allow organoids to grow much larger than their current quarter-inch or so diameter, perhaps casting off the “mini” and becoming a full-blown brain growing in a dish. Another advance getting a lot of buzz in brain organoid circles is giving one sensory input, probably via a retina, as one lab is rumored to have done.

In the new papers, according to STAT, scientists will report that the organoids survived for extended periods of time — two months in one case — and even connected to lab animals’ circulatory and nervous systems, transferring blood and nerve signals between the host animal and the implanted human cells. This is an unprecedented advancement for mini-brain research

Organoids are poised to revolutionize research on the human brain since scientists can perform tests on them that would be unethical to attempt on living humans. Scientists are debating whether these brains are “conscious,” and a whole new set of ethical concerns have arisen  for the researchers who work with them.

 

Scientists from Japan create primitive liver bud in mice

In 2013, a  team from Japan, Yokohama City University’s graduate school of medicine,  became first to grow liver cells from skin stem cells in a petri dish and then transplanted them successfully into mice.

 

Takebe and his colleagues utilized recent technique of co-culturing multiple cell types together. They utilized three different types of cells, liver cell precursors from human IPS cells (induced pluripotent stem cells), blood vessel precursors called endothelial cells, and connective tissue precursor cells called mesenchymal stem cells. The blood vessel and connective tissue precursor cells were harvested from umbilical cords. These cells got assembled into 5 milimeter sized liver buds in five days with each developing their own blood vessels. These liver buds were transplanted into mouse brain, where they were observed connecting themselves to blood vessels in a mouse. About 10 days later, the buds started working like liver breaking down human drugs and blood proteins.

 

There is need to observe the long-term effects of the transplant as stem cells tend to form tumors. The liver buds also did not achieve all the functions of a mature liver as the buds did not form a bile duct system that drives away toxins from the body.

 

Growing Lungs: Scientists Are Using Stem Cells to Try and Grow Human Lungs in a Dish

Researchers from the UCLA have found a way around some of the limitations of lung cell cultures in recreating lung scarring by growing three-dimensional “organoids” instead of relying on flat cultures. The method uses stem cells to grow pea sized three dimensional samples of lung tissue.

 

The researchers used stem cells taken from actual adult human lungs to coat tiny sticky hydrogel beads. These eventually grew and self-assembled to envelope the hydrogel beads, which were all placed inside linked wells. The resulting structure produced evenly distributed three-dimensional patterns consistent with actual air sacs like those in human lungs. While we haven’t built a fully functional lung, we’ve been able to take lung cells and place them in the correct geometrical spacing and pattern to mimic a human lung,” says UCLA associate professor of pediatric hematology and oncology and lead author Dr. Brigitte Gomperts.

 

With this technique, researchers can grow infected lung organoids so they can further study the biology of the disease. They can also conduct various drug experiments to come up with a precise, personalized treatment plan before administering anything to the patient, minimizing risks of damage. It’s also very easy to reproduce: “We can make thousands of reproducible pieces of tissue that resemble lung and contain patient-specific cells,” says materials science and engineering graduate student Dan Wilkinson.

 

World’s first bioLimb

Recently, researchers at Massachusetts General Hospital grew an entire rat arm in a dish. The bioengineered rat forelimb contained bone, cartilage, blood vessels, tendons, ligaments, and nerves, and could pave the way for entire limb transplants for amputees.

The forelimb was created with a technique called “decellularization,” which uses living donor cells to regrow organ tissue. The arm from a dead rat is turned to  white scaffold . Next, it is seeded with human endothelial cells, which recolonize the surfaces of the blood vessels and make them more robust than rat endothelial cells would. Finally, scientists inject mice cells, such as myoblasts that grow into muscles.

Though prosthetic limbs have been improving, they are far from ideal. And while the improving field of limb transplants gives hope, the patient has to take immunosuppressant drugs all their life to prevent the body rejecting the new addition because it once belonged to someone else.

 

First’ 3-D print of heart with human tissue, vessels unveiled

Scientists in Israel unveiled a 3D print of a heart with human tissue and vessels in April 2019, calling it a first and a “major medical breakthrough” that advances possibilities for transplants.

 

While it remains a far way off, scientists hope one day to be able to produce hearts suitable for transplant into humans as well as patches to regenerate defective hearts. The heart produced by researchers at Tel Aviv University is about the size of a rabbit’s. It marked “the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers,” said Tal Dvir, who led the project.

 

Heart

A team from the University of Pittsburgh, Pennsylvania, used induced pluripotent stem (iPS) cells generated from human skin cells to create precursor heart cells called MCPs. iPS cells are mature human cells “reprogrammed” into a versatile, primitive state from which they can be prompted to develop into any kind of cell of the body.

These cells developed into heart muscle, and once exposed to a blood supply, the miniature heart (grown on a mouse heart that had had all its cells removed) began to contract spontaneously. “We hope our study would be used in the future to replace a piece of tissue damaged by a heart attack, or perhaps an entire organ, in patients with heart disease.” Heart tissue regeneration has already proven successful in monkey transplants.

 

Scientists grow perfect human blood vessels in a petri dish

An organoid is a three-dimensional structure grown from stem cells that mimics an organ and can be used to study aspects of that organ in a petri dish. “Being able to build human blood vessels as organoids from stem cells is a game changer,” said the study’s senior author Josef Penninger, the Canada 150 Research Chair in Functional Genetics, director of the Life Sciences Institute at UBC and founding director of the Institute for Molecular Biotechnology of the Austrian Academy of Sciences (IMBA).

 

To tackle this problem, Penninger and his colleagues developed a groundbreaking model: three-dimensional human blood vessel organoids grown in a petri dish. These so-called “vascular organoids” can be cultivated using stem cells in the lab, strikingly mimicking the structure and function of real human blood vessels.

 

When researchers transplanted the blood vessel organoids into mice, they found that they developed into perfectly functional human blood vessels including arteries and capillaries. The discovery illustrates that it is possible to not only engineer blood vessel organoids from human stem cells in a dish, but also to grow a functional human vascular system in another species.

 

“What is so exciting about our work is that we were successful in making real human blood vessels out of stem cells,” said Reiner Wimmer, the study’s first author and a postdoctoral research fellow at IMBA. “Our organoids resemble human capillaries to a great extent, even on a molecular level, and we can now use them to study blood vessel diseases directly on human tissue.”

 

“Every single organ in our body is linked with the circulatory system. This could potentially allow researchers to unravel the causes and treatments for a variety of vascular diseases, from Alzheimer’s disease, cardiovascular diseases, wound healing problems, stroke, cancer and, of course, diabetes.”

 

Diabetes affects an estimated 420 million people worldwide. Many diabetic symptoms are the result of changes in blood vessels that result in impaired blood circulation and oxygen supply of tissues. Despite its prevalence, very little is known about the vascular changes arising from diabetes. This limitation has slowed the development of much-needed treatment.

 

One feature of diabetes is that blood vessels show an abnormal thickening of the basement membrane. As a result, the delivery of oxygen and nutrients to cells and tissues is strongly impaired, causing a multitude of health problems, such as kidney failure, heart attacks, strokes, blindness and peripheral artery disease, leading to amputations. The researchers then exposed the blood vessel organoids to a “diabetic” environment in a petri dish.

 

“Surprisingly, we could observe a massive expansion of the basement membrane in the vascular organoids,” said Wimmer. “This typical thickening of the basement membrane is strikingly similar to the vascular damage seen in diabetic patients.”

 

The researchers then searched for chemical compounds that could block thickening of the blood vessel walls. They found none of the current anti-diabetic medications had any positive effects on these blood vessel defects. However, they discovered that an inhibitor of ?-secretase, a type of enzyme in the body, prevented the thickening of the blood vessel walls, suggesting, at least in animal models, that blocking ?-secretase could be helpful in treating diabetes. The researchers say the findings could allow them to identify underlying causes of vascular disease, and to potentially develop and test new treatments for patients with diabetes.

 

3D printed EYES

The first human corneas to come out of a low-cost 3D printer were created by a team of researchers at Newcastle University in the UK.  Che Connon, professor of tissue engineering at Newcastle University, praised the medical breakthrough for utilising cheap materials in the process. Professor Connon said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

 

Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3-D printer. “This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. “Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.” The corneas is a crucial element in the outer layers of the eye used to focus vision and it is estimated some five million people suffer blindness due to cornea related wounds and diseases.

 

Scientists have now developed a solution in the form of so-called bio-ink – a liquid mix of stem cells, collagen and alginate acid. With a simple 3D printer the Newcastle scientists were able to print an artificial human cornea in less than 10 minutes. The cornea printing method could in turn create an unlimited supply of corneas ready for transplanting.

 

High-tech ‘bio-printer’

Scientists from the Universities of Sydney, Harvard, Stanford and MIT have bio-printed artificial vascular networks mimicking the body’s circulatory system that are necessary for growing large complex tissues. Using a high-tech ‘bio-printer’, the researchers fabricated a multitude of interconnected tiny fibres to serve as the mold for the artificial blood vessels.

 

They then covered the 3D printed structure with a cell-rich protein-based material, which was solidified by applying light to it. Lastly they removed the bio-printed fibres to leave behind a network of tiny channels coated with human endothelial cells, which self-organized to form stable blood capillaries in less than a week. The study reveals that the bio printed vascular networks promoted significantly better cell survival, differentiation and proliferation compared to cells that received no nutrient supply.

 

Human organ growth still far off

The bio-printing of complex and functional organs – with all the cells, proteins and blood vessels in the right place is what doctors really want and patients really need. We are still far away from that, but our finding is an important new step towards achieving these goals, according to lead author and University of Sydney researcher, Dr Luiz Bertassoni.

 

“I’m convinced engineered organs are going to be on the market soon,” said Suchitra Sumitran-Holgersson, a professor of transplantation biology at the University of Gothenburg in Sweden. She has transferred lab-made blood vessels into a handful of patients and plans to offer them more widely by 2016, pending regulatory approval. Still, she acknowledged doctors will have to watch closely for any long-term side effects, including the possibility of a higher cancer risk.

 

Meanwhile Swedish thoracic surgeon Paolo Macchiarini, has recently come under scrutiny when two of his patients who were given biosynthetic windpipes died after his initial, optimistic reports on their operations. Thus the technology of lab-grown organs is still far off to be applied in the case of humans. There are also ethical issues, the implications of creating organs like performing inhuman experiments on living organs.

 

References and Resources also include:

http://futurism.com/growing-lungs-scientists-are-using-stem-cells-to-try-and-grow-human-lungs-in-a-dish/

http://mentalfloss.com/article/65118/7-body-parts-scientists-can-grow-petri-dish

http://edition.cnn.com/2013/08/28/health/stem-cell-brain/

https://www.express.co.uk/news/science/848980/Human-pig-organ-HYBRID-organ-transplant

https://www.inverse.com/article/38240-mini-brains-organoids-rats

https://futurism.com/potential-clean-unlimited-energy

https://www.sciencedaily.com/releases/2019/01/190116130820.htm

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