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Creating a New Future: The Rise of Synthetic Organs and its Impact on Healthcare

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.

 

Advances in medical technology have given rise to a new era in healthcare, one where the creation of synthetic organs is becoming a reality. These organs have the potential to obviate the need for traditional transplants, while enhancing the quality of life for countless individuals around the world. In this article, we’ll explore the rise of synthetic organs, the impact they will have on healthcare, and what we can expect in the years to come.

First, it’s important to understand what synthetic organs are and how they are made. Synthetic organs are created using a combination of biocompatible materials, such as silicone, and living cells from animals or humans. These cells are grown in a laboratory and are used to create a functional organ that can be transplanted into a patient’s body. The result is an organ that is customized to the individual patient’s needs and has a reduced risk of rejection.

Synthetic organs advancements

Scientists are making strides in the development of synthetic organs, bringing hope for a future where complex organs such as kidneys, pancreases, and lungs can be transplanted to amputees.

Scientists have developed synthetic organs using stem cells and 3D printing technologies. Stem cells, including embryonic and adult stem cells, have been used to develop artificial versions of complex tissues, including limbs, heart tissues, windpipes, mini brains, and bladders.

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.

Scientists have also successfully 3D bioprinted several organs, such as a thyroid gland, a tibia replacement, and a patch of heart cells that actually beat. Additionally, a miniature brain, known as an organoid, has been created using stem cells. The cerebral organoid mimics the full-sized version of the brain and is made up of functional neurons, distinct layers of cortex, and other architecture. Organoids can revolutionize research on the human brain since scientists can perform tests on them that would be unethical to attempt on living humans.

Pigs are being used as ideal candidates for organ growth due to their organs’ similarity to humans. Scientists in China are close to being able to grow human organs in pigs to be transplanted to ill patients. China is home to the largest pig cloning factory in the world, which produces up to 500 cloned piglets annually. Scientists believe this is the perfect setup – the cloners grow the pigs, and the doctors add human organs.

Lungs that were made in the lab have been successfully implanted into pigs, enabling them to breathe normally. This is a significant milestone in bioengineering, as it 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. Scientists have also managed to grow perfect human blood vessels as organoids in a petri dish for the first time, which dramatically advances research of vascular diseases like diabetes.

  1. In 2013, a team from Japan’s Yokohama City University successfully grew liver cells from skin stem cells in a petri dish and transplanted them into mice.
  2. Also in 2013, scientists from the Institute of Molecular Biotechnology in Vienna, Austria created a miniature brain in the lab using stem cells.
  3. In 2015, researchers from the University of California, Los Angeles found a way to grow lung tissue using stem cells in a dish.
  4. In 2018, bioengineers developed a 3D bioprinting technique that uses natural materials, making it easier for researchers to create lifelike tissues.
  5. In January 2021, researchers at the Salk Institute for Biological Studies in California created human-pig chimeras, potentially opening the door to pigs with human brain cells.
  6. In April 2021, scientists reported in a series of papers that they were able to give mini-brains a blood supply, potentially allowing them to grow larger and connecting them to animal nervous systems.

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.

 

Two new high-tech approaches to providing organs for transplantation might ultimately both eliminate the need for organ donors and reduce the risk of tissue rejection.

The first approach is three-dimensional (3D) bioprinting, which uses “bio-ink,” a printable material made from a patient’s own cells, to print layer upon layer, creating tissue that the recipient will not reject.

This might work for relatively uncomplicated organs such as skin, but the fabrication of other, more complex organs presents imposing obstacles. The liver and kidneys, for example, produce hormone-like substances that modulate physiological processes such as blood coagulation, blood pressure, and removing toxins from the bloodstream. It is difficult to see how these closely regulated functions could be incorporated into 3D-printed organs.

The second, more promising approach is to genetically engineer animals — most often, pigs (because their organs are an appropriate size) — so that their transplanted organs will not be rejected. In effect, it uses genetic engineering to grow “humanized” tissues and organs in animals. Two separate, very small clinical trials have already been performed – a pig heart transplanted into a patient with terminal heart disease and a pig kidney implanted in a brain-dead patient. The heart transplant patient died two months post-transplant (apparently from a latent virus in the organ), and the kidneys worked well until the experiment was terminated after three days. These are considered encouraging early results.

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.

For in-depth understanding on Synthetic organs and applications please visit: The Future of Organ Transplantation: Exploring the Promise of Synthetic Organs

 

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.

 

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.

3D printing or bioprinting

Artificial organs are being developed using 3D printing or bioprinting. Recently, researchers at Newcastle University in the UK created the first human corneas to come out of a low-cost 3D printer. Stephen Westaby, from the John Radcliffe Hospital in Oxford, predicts that within ten years, heart transplants will no longer be necessary except for people with congenital heart damage, where only a new heart will do.

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.

Advantages of Synthetic Organs

The development of synthetic organs has the potential to revolutionize the field of organ transplantation. Traditional transplants are limited by the availability of donor organs, which can be difficult to obtain and often come with a risk of rejection. Synthetic organs offer an alternative that is more reliable and can be manufactured at scale to meet the growing demand for organs.

One of the most significant benefits of synthetic organs is the potential to enhance the quality of life for patients. With synthetic organs, patients can avoid the pain and discomfort of surgery, as well as the risks associated with traditional transplantation methods. Additionally, synthetic organs can be customized to match the unique needs of each patient, providing a more personalized and effective treatment option.

But the rise of synthetic organs also raises ethical considerations that must be addressed. For example, there is the potential for inequality in access to these technologies, with those who can afford them having an advantage over those who cannot. There are also concerns about the use of animal cells and tissues in the creation of synthetic organs, which raises questions about animal welfare and the use of living creatures for medical purposes.

Despite these challenges, ongoing research and development in synthetic organs are paving the way for new treatments and cures for a wide range of conditions and diseases. As the technology continues to advance, we can expect to see a range of exciting new possibilities emerge, from more efficient and effective transplantation techniques to the development of entirely new therapies and treatment approaches.

The impact of synthetic organs on the healthcare industry cannot be overstated. From reducing the need for traditional transplants to enhancing the quality of life for patients, synthetic organs have the potential to transform the way we approach medical treatment. As we continue to explore the possibilities of this groundbreaking technology, we can look forward to a future where patients have access to safe, effective, and personalized treatment options that enhance their health and well-being.

In conclusion, the rise of synthetic organs represents a new frontier in healthcare, offering exciting new possibilities for patients and healthcare providers alike. While there are challenges that must be addressed, the potential of this technology is vast, and as it continues to evolve and mature, we can expect to see significant progress in the coming years and decades. Whether through improved biocompatibility, increased functionality, or more efficient manufacturing processes, the future of synthetic organ transplantation is bright, and offers hope to countless patients in need around the world.

 

 

 

 

 

 

 

 

 

 

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

About Rajesh Uppal

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