The Future of Medicine: The “Human Body-on-a-Chip”

bodyonachip One of the aims of modern medicine is perfecting the way we tests treatments and drugs, so that the lengthy guess-work and clinical trials can be shortened or even cut out of the equation. While this would not only ensure the speedier delivery of drugs to market, it would also eliminate the need for animal testing, something which has become increasingly common and controversial in recent years.

Over the last century, animal testing has expanded from biomedical research to included things like drug, chemical, and cosmetic testing. One 2008 study conducted by The Guardian estimated that 115 million animals are used a year for scientific research alone. It is therefore no surprise that opposition is growing, and that researchers, regulators and even military developers are looking for more accurate, efficient, and cruelty-free alternatives.

bodyonachip1Enter the National Insitute of Health in Besthesda, Maryland; where researchers have teamed up with the FDA and even DARPA to produce a major alternative. Known as the “Human Body-on-a Chip”, this device is similar to other “Organs-on-a-chip” in that it is basically a small, flexible pieces of plastic with hollow micro-fluidic channels lined with human cells that can mimic human systems far more effectively than simple petri dish cell cultures.

Dan Tagle, the associate director of the NIH’s National Center for Advancing Translational Sciences, explained the benefits of this technology as follows:

If our goal is to create better drugs, in a way that is much more efficient, time and cost-wise, I think it’s almost inevitable that we will have to either minimize or do away with animal testing.

https://i0.wp.com/images.medicaldaily.com/sites/medicaldaily.com/files/styles/large/public/2014/03/18/new-technology-may-obviate-need-animal-testing.jpgWhat’s more, chips like this one could do away with animal testing entirely, which is not only good news for animals and activists, but drug companies themselves. As it stands, pharmaceutical companies have hit a wall in developing new drugs, with roughly 90% failing in human clinical trials based on safety and effectiveness. One reason for this high rate of failure is that drugs that first seem promising in rodents often don’t have the same response in people.

In fact, so-called “animal models” are only typically 30% to 60% predictive of human responses, and there are potentially life-saving drug therapies that never make it to human clinical trials because they’re toxic to mice. In these cases, there’s no way to measure the lost opportunity when animals predict the wrong response. And all told, it takes an average of 14 years and often billions of dollars to actually deliver a new drug to the market.

bodyonachip2According to Geraldine Hamilton, a senior staff scientist at Harvard University’s Wyss Institute for Biologically Inspired Engineering, it all began five years ago with the “lung-on-a-chip”:

We’ve also got the lung, gut, liver and kidney. We’re working on skin. The goal is really to do the whole human body, and then we can fluidically link multiple chips to capture interactions between different organs and eventually recreate a body on a chip.

This has led to further developments in the technology, and Hamilton is now launching a new startup company to bring it to the commercial market. Emulate, the new startup that will license Wyss’s technology, isn’t looking to literally create a human body but rather to represent its “essential functions” and develop a platform that’s easy for all scientists and doctors to use, says Hamilton, who will become Emulate’s president and chief scientific officer.

lung-on-a-chip-5Borrowing microfabrication techniques from the semiconductor industry, each organ-on-a-chip is built with small features – such as channels, vessels, and flexible membranes – designed to recreate the flow and forces that cells experience inside a human body. All that’s needed are different chips with different culture of human cells; then researchers can performed tests to see how drugs work in one region of the body before being metabolized by the liver.

This might one day help the military to test treatments for biological or chemical weapons, a process that is unethical (and illegal) with humans, and cruel and often inaccurate with animals. Hospitals may also be able to use a patient’s own stem cells to develop and test “personalized” treatments for their disease, and drug companies could more quickly screen promising new drugs to see if they are effective and what (if any) side effects they have on the body’s organs.

It’s a process that promises speedier tests, quicker delivery, a more cost-effective medical system, and the elimination of cruel and often inaccurate animal testing. Can you say win-win-win?

Source: fastcoexist.com, ncats.nih.gov, wyss.harvard.edu, theguardian.com

Immortality Inc: Regrowing Body Parts

https://i0.wp.com/images.gizmag.com/hero/lizardtails-2.jpgAnyone who has ever observed a lizard must not have failed to notice that they are capable of detaching their tails, and then regenerating them from scratch. This propensity for “spontaneous regeneration” is something that few organisms possess, and mammals are sadly not one of them. But thanks to a team of Arizona State University scientists, the genetic recipe behind this ability has finally been unlocked.

This breakthrough is a small part of a growing field of biomedicine that seeks to improve human health by tampering with the basic components (i.e. our DNA). The research, which was funded by grants from the National Institutes of Health and Arizona Biomedical Research Commission, also involved scientists from the University of Arizona College of Medicine, Translational Genomic Research Institute, and Michigan State University.

dna_cancerAccording to Prof. Kenro Kusumi, lead author of a paper on the genetic study, lizards are the most closely-related animals to humans that can regenerate entire appendages. They also share the same genetic language as us, so it’s theoretically possible that we could do what they do, if only we knew which genes to use and in what amounts. As Kusumi explains in the paper, which was published Aug. 20 in the journal PLOS ONE. :

Lizards basically share the same toolbox of genes as humans. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals, and wound healing.

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

calico-header-640x353 It takes lizards more than 60 days to regenerate a functional tail — forming a complex regenerating structure with cells growing into different tissues at a number of sites along the tail. According to Katsumi, harnessing this would be a boon for medicine for obvious reasons:

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

The researchers also hope their findings will also help repairing birth defects and treating diseases such as arthritis. Given time, and enough positive results, I think it would be fair to expect that Google’s Clinical Immortality subsidiary – known as Calico – will buy up all the necessary rights. Then, it shouldn’t be more than a decade before a gene treatments is produced that will allow for spontaneous regeneration and the elimination of degenerative diseases.

The age of post-mortal is looming people. Be scared/enthused!

Sources: kurzweil.net, gizmag.com

Biomedical Breakthroughs: Vascular Network Bioprinting

bioprintingThe ability to generate biological tissues using 3-D printing methods – aka. “bioprinting” – may one day help medical researchers and hospitals to create artificial, on-demand custom body parts and organs for patients. And numerous recent advancements – such as the creation of miniature kidneys, livers, and stem cell structures – are bringing that possibility closer to reality.

And now, according to a new study produced by researchers from the University of Sydney, it is now possible to bioprint artificial vascular networks that mimic the body’s circulatory system. Being able to bio-print an artificial vascular network would give us the ability to keep tissue and organs alive where previously it would not have been possible. The body’s vascular network enables it to transport blood and, therefore, oxygen and nutrients, to tissues and organs.

vascularIt also provides a means of transporting waste materials away from tissues and organs. Dr. Luiz Bertassoni. the lead author of the study explained:

Cells die without an adequate blood supply because blood supplies oxygen that’s necessary for cells to grow and perform a range of functions in the body. To illustrate the scale and complexity of the bio-engineering challenge we face, consider that every cell in the body is just a hair’s width from a supply of oxygenated blood. Replicating the complexity of these networks has been a stumbling block preventing tissue engineering from becoming a real world clinical application.

In order to solve this problem, the researchers used a bioprinter to create a framework of tiny interconnected fibers to serve as a mold. The structure was then covered with a “cell-rich protein-based material” and solidified using light. The fibers were removed to leave a network of tiny channels that formed into stable human blood-capillaries within just a week’s time.

stem_cells3According to the University of Sydney study, the technique demonstrated better cell survival, differentiation and proliferation compared to cells that received no nutrient supply. In addition, it provides the ability to create large, life-supporting three-dimensional, micro-vascular channels quickly and with the precision required for application to different individuals.

This is a major step forward for the bioprinting industry, according to Bertassoni:

While recreating little parts of tissues in the lab is something that we have already been able to do, the possibility of printing three-dimensional tissues with functional blood capillaries in the blink of an eye is a game changer.

bioprinter1In addition, Bertassoni claims that the ultimate aim of the research is for patients to be able to walk into a hospital and have a full organ printed with all the cells, proteins and blood vessels in the right place:

We are still far away from that, but our research is addressing exactly that. Our finding is an important new step towards achieving these goals. At the moment, we are pretty much printing ‘prototypes’ that, as we improve, will eventually be used to change the way we treat patients worldwide.

Bioprinting that uses a patient’s own DNA to generate custom-made organs and tissues offers a world of medical possibilities in which organ donors are no longer necessary, and the risk of rejection and incompatibility is negligible. Not only that, it will usher in a world where no injury is permanent and prosthetics are a thins of the past.

Sources: gizmag.com, sydney.edu.au

The Future of Medicine: Adult Stem Cells Cloned for First Time!

3dstemcellsBioprinting and the creation of artificial organs holds a great deal of promise for the field of medicine. By simply layering “bioinks” – which are are made up of stem cells – researchers have been able to form cell cultures and create artificial tissues, ranging from miniature kidneys and livers to cartilage and skin. The only drawback is that the base material in this operation – i.e. stem cells – has posed certain limitations, mainly in that scientists have been unable to clone them from specific patients.

 

However, thanks to a new research method, researchers have just succeeded in returning adult somatic (body) cells to a virgin stem cell state which can then be made into nearly any tissue. This breakthrough is likely reinvigorate efforts to use such cells to make patient-specific replacement tissues for degenerative diseases, for example to replace pancreatic cells in patients with type 1 diabetes. It’s a huge breakthrough in stem cell research in what has already been an exciting year. 

stem_cells2Last May, researchers from the Oregon Health & Science University in Beaverton perfected a process to therapeutically clone human embryos – thus producing cells that are genetically identical to a donor for the purpose of treating disease. In this case, the cells carried genomes taken from fetal cells and the cells of an eight-month-old baby. Then last month, two research groups announced that they had cloned stem cells from adult cells, independently and within a few days of each other.

The first announcement came on April 17th, when researchers at the CHA University in Seoul reported in Cell Stem Cell that they had cloned embryonic stem-cell (ES cell) lines made using nuclei from two healthy men, aged 35 and 75. On then on April 28th, researchers at the New York Stem Cell Foundation have taken body cells from a diabetic patient, transplanted the nucleus from those cells into a donor egg that has had its genetic material stripped, and allowed it to begin dividing.

stem_cells3In the latter case, the researchers reported that the new cells not only began dividing normally, but also began producing insulin naturally—a breakthrough that could eventually lead to a cure for the disease, in which patients are normally reliant on daily insulin injections. As Doctor Egli, leader of the New York Stem Cell Foundation team, said in a conference call with reporters:

We show for the first time that we are able to derive diploid, patient-specific stem cells and are able to induce these stem cells into becoming cells that produce and secrete insulin, showing that this technique should be useful for the development of cell-replacement therapies for diabetes.

The work was published in the journal Nature. Although not noted in the paper, Egli says that the cells work just as well as normally-functioning pancreas cells in non-diabetic humans.

bioprinted heartThe process behind both breakthroughs is known as somatic-cell nuclear transfer, which involves transplanting the “cloned” nucleus of a cell into an existing one that has had its nucleus removed. This is important because it is generally adults who stand to benefit the most from a fresh supply of cells to revitalize their ailing organs. And in addition to age-related treatment, this process offers options for the treatment of diseases that can cause damage to organs with time – in this case, Type 1 diabetes.

However, this day is still many years away, owing to numerous challenges posed by the process. At present, the technique is expensive, technically difficult, and ethical considerations are still an issue since it involves creating an embryo for the purpose of harvesting its cells lone. Obtaining human eggs also requires regulatory clearance to perform an invasive procedure on healthy young women, who are paid for their time and discomfort.

As a result, it is likely to be many more years before this process will becomes medically and commercially viable. That is to say, we won’t be seeing hospitals with their own bioprinting clinics where patients can simply go in, donate their cells, and swap out a diseased liver or damaged pancreas anytime soon. And as long as donated embryos are still a bottleneck, we can expect ethical and legal hurdles to remain in place as well.

Sources: extremetech.com, nature.com, motherboard.vice.com, cell.com

 

The Future of Medicine: Replacement Ears and “Mini Hearts”

biomedicineBiomedicine is doing some amazing things these days, so much so that I can hardly keep up with the rate of developments. Just last month, two amazing ones were made, offering new solutions for replacing human tissue and treating chronic conditions. The first has to do with a new method of growing human using a patients own DNA, while the second involves using a patient’s own heart tissue to create “mini hearts” to aid in circulation.

The first comes from London’s Great Ormond Street Hospital, where researchers are working on a process that will grow human ears using genetic material taken from a patient’s own fat tissue. Building upon recent strides made in the field of bioprinting, this process will revolution reconstructive surgery as we know it. It also seeks to bring change to an area of medicine which, despite being essential for accident victims, has been sadly lacking in development.

replacement_earCurrently, the procedure to repair damaged or non-existent cartilage in the ear involves an operation that is usually carried out when the patient is a child. For the sake of this procedure, cartilage is extracted from the patient’s ribs and painstakingly crafted into the form of an ear before being grafted back onto the individual. Whilst this method of reconstruction achieves good results, it also comes with its share of unpleasant side effects.

Basically, the patient is left with a permanent defect around the area from where the cells were harvested, as the cartilage between the ribs does not regenerate. In this new technique, the cartilage cells are engineered from mesenchymal stem cells, extracted from the child’s abdominal adipose (fat) tissue. The benefit of this new system is that unlike the cartilage in the ribs, the adipose tissue regenerates, therefore leaving no long-term defect to the host.

stem_cells1There is also the potential to begin reconstructive treatment with stem cells derived from adipose tissue earlier than previously possible, as it takes time for the ribs to grow enough cartilage to undergo the procedure. As Dr. Patrizia Ferretti, a researcher working on the project, said in a recent interview:

One of the main benefits in using the patient’s own stem cells is that there is no need for immune suppression which would not be desirable for a sick child, and would reduce the number of severe procedures a child needs to undergo.

To create the form of the ear, a porous polymer nano-scaffold is placed in with the stem cells. The cells are then chemically induced to become chondrocytes (aka. cartilage cells) while growing into the holes in the scaffold to create the shape of the ear. According to Dr. Ferretti, cellularized scaffolds – themselves a recent medical breakthrough – are much better at integrating than fully-synthetic implants, which are more prone to extrusion and infection.

cartilage2Dr. Ferretti continued that:

While we are developing this approach with children with ear defects in mind, it could ultimately be utilized in other types of reconstructive surgery both in children and adults.

Basically, this new, and potentially more advantageous technique would replace the current set of procedures in the treatment of defects in cartilage in children such as microtia, a condition which prevents the ear from forming correctly. At the same time, the reconstructive technology also has the potential to be invaluable in improving the quality of life of those who have been involved in a disfiguring accident or even those injured in the line of service.

mini_hearts`Next up, there is the “mini heart” created by Dr. Narine Sarvazyan of George Washington University in Washington D.C.. Designed to be wrapped around individual veins, these cuffs of rhythmically-contracting heart tissue are a proposed solution to the problem of chronic venous insufficiency – a condition where leg veins suffer from faulty valves, which prevents oxygen-poor blood from being pumped back to the heart.

Much like process for creating replacement ears, the mini hearts are grown  by coaxing a patient’s own adult stem cells into becoming cardiac cells. When one of those cuffs is placed around a vein, its contractions aid in the unidirectional flow of blood, plus it helps keep the vein from becoming distended. Additionally, because it’s grown from the patient’s own cells, there’s little chance of rejection. So far, the cuffs have been grown in the lab, where they’ve also been tested. But soon, Sarvazyan hopes to conduct animal trials.

mini_hearts2As Sarvazyan explained, the applications here far beyond treating venous insufficiency. In addition, there are the long-range possibilities for organ replacement:

We are suggesting, for the first time, to use stem cells to create, rather than just repair damaged organs. We can make a new heart outside of one’s own heart, and by placing it in the lower extremities, significantly improve venous blood flow.

One of the greatest advantages of the coming age of biomedicine is the ability to replace human limbs, organs and tissue using organic substitutions. And the ability to grow these from the patient’s own tissue is a major plus, in that it cuts down on the development process and ensures a minimal risk of rejection. On top of all that, the ability to create replacement organs would also significantly cut down on the costs of replacement tissue, as well as the long waiting periods associated with donor lists.

Imagine that, if you will. A future where a patient suffering from liver, kidney, circulatory, or heart problems is able to simply visit their local hospital or clinic, donate a meager supply of tissue, and receive a healthy, fully-compatible replacement after an intervening period (days or maybe even hours). The words “healthy living” will achieve new meaning!

 

Sources: gizmag.com, (2), nanomedjournal.com

The Future is Here: Handheld 3-D Bioprinter

handheld_bioprinterSince it’s inception, bioprinting has offered medical science and astounding range of applications, with new being added every day. In just the past few years, researchers have found ways to create 3-D printed cartilage, replacement skin, and even miniature kidneys and livers using stem cells. And now, with this latest development, doctor’s may be able to “draw” replacement tissue as easily as they scrawl their signatures on a prescription pad.

It’s known as the BioPen, a handheld surgical device that works a little like a mini-3-D printer may soon be used to help repair damaged bones. Developed by Austrian researchers, the pen allows a surgeon to draw layers of stem cells directly at the site of an injury. Much like a a 3-D printer deposits plastic one layer at a time, the BioPen deposits gel in layers to create a 3-D structure.

BioPenAfter filling the damaged bone with the cells – mixed with a biodegradable seaweed extract to hold everything together- an ultraviolet light on the pen sets the gel in place. After the cells are in place, they multiply and eventually form functioning tissue. The device can also be used to apply growth factors to stimulate cell growth and other drugs (like cortisone) directly to where they are needed.

University of Wollongong professor Gordon Wallace, one of the researchers who is working on the project along with a team from the University of Melbourne, expressed the benefits of the device this way:

Biology works in 3-D. The ability to provide an appropriate structural environment for the stem cells enables more effective development into the appropriate tissue.

3dstemcellsIn the past, surgeons might have just injected stem cells to the desired area. But now, using the pen to build a small scaffold out of the gel, the cells can be better protected and more likely to survive. The researchers say it’s also easier to be precise with the pen in hand, and the whole process takes less time than surgeries would have in the past.

To further illustrate the uses and applications of additive manufacturing, the prototype itself was built in the researchers’ lab using a 3-D printer. According to Wallace, next-generation fabrication techniques not only made it possible to easily build the pen, but they also make it possible to quickly iterate new versions of the hardware.

bioprinted heartAnd while their partners at St. Vincent’s Hospital in Melbourne are working on optimizing the cell material, Wallace and his team of researchers will begin conducting animal trials with the BioPen, beginning later this year. If all goes well, the device could be undergoing human trials sometime in 2015, and available in hospitals in just a few years time.

And combined with other procedures that can generate replacement tissue (eyes, organs, skin), we will be looking at the age of biomedicine in full bloom!

Source: fastcoexist.com

The Future is Here: 3-D Printed Eye Cells

printed_eyecells3In the past few years, medical researchers have been able to replicate real, living tissues samples using 3-D printing technology – ranging from replacement ears and printed cartilage to miniature kidneys and even liver cells. Well now, thanks to a team of researchers from the University of Cambridge, eye cells have been added to that list.

Using a standard ink-jet printer to form layers of two types of cells,  the research team managed to print two types of central nervous system cells from the retinas of adult rats – ganglion cells (which transmit information from the eye to the brain), and glial cells (which provide protection and support for neurons). The resulting cells were able to grow normally and remain healthy in culture.

printed_eyecells2Ink-jet printing has been used to deposit cells before, but this is the first time cells from an adult animal’s central nervous system have been printed. The research team published its research in the IOP Publishing’s open-access journal Biofabrication and plans to extend this study to print other cells of the retina and light-sensitive photoreceptors.

In the report, Keith Martin and Barbara Lorber – the co-authors of the paper who work at the John van Geest Centre for Brain Repair at the University of Cambridge – explained the experiment in detail:

Our study has shown, for the first time, that cells derived from the mature central nervous system, the eye, can be printed using a piezoelectric inkjet printer. Although our results are preliminary and much more work is still required, the aim is to develop this technology for use in retinal repair in the future.

printed_eyecellsThis is especially good news for people with impaired visual acuity, or those who fear losing their sight, as it could lead to new therapies for retinal disorders such as blindness and macular degeneration. Naturally, more tests are needed before human trials can begin. But the research and its conclusions are quite reassuring that eye cells can not only be produced synthetically, but will remain healthy after they are produced.

Clara Eaglen, a spokesperson for the Royal National Institute of Blind People (RNIB), had this to say about the breakthrough:

The key to this research, once the technology has moved on, will be how much useful vision is restored. Even a small bit of sight can make a real difference, for some people it could be the difference between leaving the house on their own or not. It could help boost people’s confidence and in turn their independence.

printed_eyecells1Combined with bionic eyes that are now approved for distribution in the US, and stem cell treatments that have restores sight in mice, this could be the beginning of the end of blindness. And with all the strides being made in bioprinting and biofabrication, it could also be another step on the long road to replacement organs and print-on-demand body parts.

Sources: news.cnet.com, singularityhub.com, cam.ca.uk, bbc.co.uk