Tag Archives: Stem cells
Engineers have built microrobots to perform all sorts of tasks in the body, and can now add to that list another key skill: delivering stem cells. In a paper published today in Science Robotics, researchers describe propelling a magnetically-controlled, stem-cell-carrying bot through a live mouse.
Under a rotating magnetic field, the microrobots moved with rolling and corkscrew-style locomotion. The researchers, led by Hongsoo Choi and his team at the Daegu Gyeongbuk Institute of Science & Technology (DGIST), in South Korea, also demonstrated their bot’s moves in slices of mouse brain, in blood vessels isolated from rat brains, and in a multi-organ-on-a chip.
The invention provides an alternative way to deliver stem cells, which are increasingly important in medicine. Such cells can be coaxed into becoming nearly any kind of cell, making them great candidates for treating neurodegenerative disorders such as Alzheimer’s.
But delivering stem cells typically requires an injection with a needle, which lowers the survival rate of the stem cells, and limits their reach in the body. Microrobots, however, have the potential to deliver stem cells to precise, hard-to-reach areas, with less damage to surrounding tissue, and better survival rates, says Jin-young Kim, a principle investigator at DGIST-ETH Microrobotics Research Center, and an author on the paper.
The virtues of microrobots have inspired several research groups to propose and test different designs in simple conditions, such as microfluidic channels and other static environments. A group out of Hong Kong last year described a burr-shaped bot that carried cells through live, transparent zebrafish.
The new research presents a magnetically-actuated microrobot that successfully carried stem cells through a live mouse. In additional experiments, the cells, which had differentiated into brain cells such as astrocytes, oligodendrocytes, and neurons, transferred to microtissues on the multi-organ-on-a-chip. Taken together, the proof-of-concept experiments demonstrate the potential for microrobots to be used in human stem cell therapy, says Kim.
The team fabricated the robots with 3D laser lithography, and designed them in two shapes: spherical and helical. Using a rotating magnetic field, the scientists navigated the spherical-shaped bots with a rolling motion, and the helical bots with a corkscrew motion. These styles of locomotion proved more efficient than that from a simple pulling force, and were more suitable for use in biological fluids, the scientists reported.
The big challenge in navigating microbots in a live animal (or human body) is being able to see them in real time. Imaging with fMRI doesn’t work, because the magnetic fields interfere with the system. “To precisely control microbots in vivo, it is important to actually see them as they move,” the authors wrote in their paper.
That wasn’t possible during experiments in a live mouse, so the researchers had to check the location of the microrobots before and after the experiments using an optical tomography system called IVIS. They also had to resort to using a pulling force with a permanent magnet to navigate the microrobots inside the mouse, due to the limitations of the IVIS system.
Kim says he and his colleagues are developing imaging systems that will enable them to view in real time the locomotion of their microrobots in live animals. Continue reading
Life is pretty different now than it was 20 years ago, or even 10 years ago. It’s sort of exciting, and sort of scary. And hold onto your hat, because it’s going to keep changing—even faster than it already has been.
The good news is, maybe there won’t be too many big surprises, because the future will be shaped by trends that have already been set in motion. According to Singularity University co-founder and XPRIZE founder Peter Diamandis, a lot of these trends are unstoppable—but they’re also pretty predictable.
At SU’s Global Summit, taking place this week in San Francisco, Diamandis outlined some of the meta-trends he believes are key to how we’ll live our lives and do business in the (not too distant) future.
Increasing Global Abundance
Resources are becoming more abundant all over the world, and fewer people are seeing their lives limited by scarcity. “It’s hard for us to realize this as we see crisis news, but what people have access to is more abundant than ever before,” Diamandis said. Products and services are becoming cheaper and thus available to more people, and having more resources then enables people to create more, thus producing even more resources—and so on.
Need evidence? The proportion of the world’s population living in extreme poverty is currently lower than it’s ever been. The average human life expectancy is longer than it’s ever been. The costs of day-to-day needs like food, energy, transportation, and communications are on a downward trend.
Take energy. In most of the world, though its costs are decreasing, it’s still a fairly precious commodity; we turn off our lights and our air conditioners when we don’t need them (ideally, both to save money and to avoid wastefulness). But the cost of solar energy has plummeted, and the storage capacity of batteries is improving, and solar technology is steadily getting more efficient. Bids for new solar power plants in the past few years have broken each other’s records for lowest cost per kilowatt hour.
“We’re not far from a penny per kilowatt hour for energy from the sun,” Diamandis said. “And if you’ve got energy, you’ve got water.” Desalination, for one, will be much more widely feasible once the cost of the energy needed for it drops.
Knowledge is perhaps the most crucial resource that’s going from scarce to abundant. All the world’s knowledge is now at the fingertips of anyone who has a mobile phone and an internet connection—and the number of people connected is only going to grow. “Everyone is being connected at gigabit connection speeds, and this will be transformative,” Diamandis said. “We’re heading towards a world where anyone can know anything at any time.”
Increasing Capital Abundance
It’s not just goods, services, and knowledge that are becoming more plentiful. Money is, too—particularly money for business. “There’s more and more capital available to invest in companies,” Diamandis said. As a result, more people are getting the chance to bring their world-changing ideas to life.
Venture capital investments reached a new record of $130 billion in 2018, up from $84 billion in 2017—and that’s just in the US. Globally, VC funding grew 21 percent from 2017 to a total of $207 billion in 2018.
Through crowdfunding, any person in any part of the world can present their idea and ask for funding. That funding can come in the form of a loan, an equity investment, a reward, or an advanced purchase of the proposed product or service. “Crowdfunding means it doesn’t matter where you live, if you have a great idea you can get it funded by people from all over the world,” Diamandis said.
All this is making a difference; the number of unicorns—privately-held startups valued at over $1 billion—currently stands at an astounding 360.
One of the reasons why the world is getting better, Diamandis believes, is because entrepreneurs are trying more crazy ideas—not ideas that are reasonable or predictable or linear, but ideas that seem absurd at first, then eventually end up changing the world.
Everyone and Everything, Connected
As already noted, knowledge is becoming abundant thanks to the proliferation of mobile phones and wireless internet; everyone’s getting connected. In the next decade or sooner, connectivity will reach every person in the world. 5G is being tested and offered for the first time this year, and companies like Google, SpaceX, OneWeb, and Amazon are racing to develop global satellite internet constellations, whether by launching 12,000 satellites, as SpaceX’s Starlink is doing, or by floating giant balloons into the stratosphere like Google’s Project Loon.
“We’re about to reach a period of time in the next four to six years where we’re going from half the world’s people being connected to the whole world being connected,” Diamandis said. “What happens when 4.2 billion new minds come online? They’re all going to want to create, discover, consume, and invent.”
And it doesn’t stop at connecting people. Things are becoming more connected too. “By 2020 there will be over 20 billion connected devices and more than one trillion sensors,” Diamandis said. By 2030, those projections go up to 500 billion and 100 trillion. Think about it: there’s home devices like refrigerators, TVs, dishwashers, digital assistants, and even toasters. There’s city infrastructure, from stoplights to cameras to public transportation like buses or bike sharing. It’s all getting smart and connected.
Soon we’ll be adding autonomous cars to the mix, and an unimaginable glut of data to go with them. Every turn, every stop, every acceleration will be a data point. Some cars already collect over 25 gigabytes of data per hour, Diamandis said, and car data is projected to generate $750 billion of revenue by 2030.
“You’re going to start asking questions that were never askable before, because the data is now there to be mined,” he said.
Increasing Human Intelligence
Indeed, we’ll have data on everything we could possibly want data on. We’ll also soon have what Diamandis calls just-in-time education, where 5G combined with artificial intelligence and augmented reality will allow you to learn something in the moment you need it. “It’s not going and studying, it’s where your AR glasses show you how to do an emergency surgery, or fix something, or program something,” he said.
We’re also at the beginning of massive investments in research working towards connecting our brains to the cloud. “Right now, everything we think, feel, hear, or learn is confined in our synaptic connections,” Diamandis said. What will it look like when that’s no longer the case? Companies like Kernel, Neuralink, Open Water, Facebook, Google, and IBM are all investing billions of dollars into brain-machine interface research.
Increasing Human Longevity
One of the most important problems we’ll use our newfound intelligence to solve is that of our own health and mortality, making 100 years old the new 60—then eventually, 120 or 150.
“Our bodies were never evolved to live past age 30,” Diamandis said. “You’d go into puberty at age 13 and have a baby, and by the time you were 26 your baby was having a baby.”
Seeing how drastically our lifespans have changed over time makes you wonder what aging even is; is it natural, or is it a disease? Many companies are treating it as one, and using technologies like senolytics, CRISPR, and stem cell therapy to try to cure it. Scaffolds of human organs can now be 3D printed then populated with the recipient’s own stem cells so that their bodies won’t reject the transplant. Companies are testing small-molecule pharmaceuticals that can stop various forms of cancer.
“We don’t truly know what’s going on inside our bodies—but we can,” Diamandis said. “We’re going to be able to track our bodies and find disease at stage zero.”
The world is far from perfect—that’s not hard to see. What’s less obvious but just as true is that we’re living in an amazing time. More people are coming together, and they have more access to information, and that information moves faster, than ever before.
“I don’t think any of us understand how fast the world is changing,” Diamandis said. “Most people are fearful about the future. But we should be excited about the tools we now have to solve the world’s problems.”
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Lizards can regrow entire limbs. Flatworms, starfish, and sea cucumbers regrow entire bodies. Sharks constantly replace lost teeth, often growing over 20,000 teeth throughout their lifetimes. How can we translate these near-superpowers to humans?
The answer: through the cutting-edge innovations of regenerative medicine.
While big data and artificial intelligence transform how we practice medicine and invent new treatments, regenerative medicine is about replenishing, replacing, and rejuvenating our physical bodies.
In Part 5 of this blog series on Longevity and Vitality, I detail three of the regenerative technologies working together to fully augment our vital human organs.
Replenish: Stem cells, the regenerative engine of the body
Replace: Organ regeneration and bioprinting
Rejuvenate: Young blood and parabiosis
Let’s dive in.
Replenish: Stem Cells – The Regenerative Engine of the Body
Stem cells are undifferentiated cells that can transform into specialized cells such as heart, neurons, liver, lung, skin and so on, and can also divide to produce more stem cells.
In a child or young adult, these stem cells are in large supply, acting as a built-in repair system. They are often summoned to the site of damage or inflammation to repair and restore normal function.
But as we age, our supply of stem cells begins to diminish as much as 100- to 10,000-fold in different tissues and organs. In addition, stem cells undergo genetic mutations, which reduce their quality and effectiveness at renovating and repairing your body.
Imagine your stem cells as a team of repairmen in your newly constructed mansion. When the mansion is new and the repairmen are young, they can fix everything perfectly. But as the repairmen age and reduce in number, your mansion eventually goes into disrepair and finally crumbles.
What if you could restore and rejuvenate your stem cell population?
One option to accomplish this restoration and rejuvenation is to extract and concentrate your own autologous adult stem cells from places like your adipose (or fat) tissue or bone marrow.
These stem cells, however, are fewer in number and have undergone mutations (depending on your age) from their original ‘software code.’ Many scientists and physicians now prefer an alternative source, obtaining stem cells from the placenta or umbilical cord, the leftovers of birth.
These stem cells, available in large supply and expressing the undamaged software of a newborn, can be injected into joints or administered intravenously to rejuvenate and revitalize.
Think of these stem cells as chemical factories generating vital growth factors that can help to reduce inflammation, fight autoimmune disease, increase muscle mass, repair joints, and even revitalize skin and grow hair.
Over the last decade, the number of publications per year on stem cell-related research has increased 40x, and the stem cell market is expected to increase to $297 billion by 2022.
Rising research and development initiatives to develop therapeutic options for chronic diseases and growing demand for regenerative treatment options are the most significant drivers of this budding industry.
Biologists led by Kohji Nishida at Osaka University in Japan have discovered a new way to nurture and grow the tissues that make up the human eyeball. The scientists are able to grow retinas, corneas, the eye’s lens, and more, using only a small sample of adult skin.
In a Stanford study, seven of 18 stroke victims who agreed to stem cell treatments showed remarkable motor function improvements. This treatment could work for other neurodegenerative conditions such as Alzheimer’s, Parkinson’s, and ALS.
Doctors from the USC Neurorestoration Center and Keck Medicine of USC injected stem cells into the damaged cervical spine of a recently paralyzed 21-year-old man. Three months later, he showed dramatic improvement in sensation and movement of both arms.
In 2019, doctors in the U.K. cured a patient with HIV for the second time ever thanks to the efficacy of stem cells. After giving the cancer patient (who also had HIV) an allogeneic haematopoietic (e.g. blood) stem cell treatment for his Hodgkin’s lymphoma, the patient went into long-term HIV remission—18 months and counting at the time of the study’s publication.
Replace: Organ Regeneration and 3D Printing
Every 10 minutes, someone is added to the US organ transplant waiting list, totaling over 113,000 people waiting for replacement organs as of January 2019.
Countless more people in need of ‘spare parts’ never make it onto the waiting list. And on average, 20 people die each day while waiting for a transplant.
As a result, 35 percent of all US deaths (~900,000 people) could be prevented or delayed with access to organ replacements.
The excessive demand for donated organs will only intensify as technologies like self-driving cars make the world safer, given that many organ donors result from auto and motorcycle accidents. Safer vehicles mean less accidents and donations.
Clearly, replacement and regenerative medicine represent a massive opportunity.
Enter United Therapeutics CEO, Dr. Martine Rothblatt. A one-time aerospace entrepreneur (she was the founder of Sirius Satellite Radio), Rothblatt changed careers in the 1990s after her daughter developed a rare lung disease.
Her moonshot today is to create an industry of replacement organs. With an initial focus on diseases of the lung, Rothblatt set out to create replacement lungs. To accomplish this goal, her company United Therapeutics has pursued a number of technologies in parallel.
3D Printing Lungs
In 2017, United teamed up with one of the world’s largest 3D printing companies, 3D Systems, to build a collagen bioprinter and is paying another company, 3Scan, to slice up lungs and create detailed maps of their interior.
This 3D Systems bioprinter now operates according to a method called stereolithography. A UV laser flickers through a shallow pool of collagen doped with photosensitive molecules. Wherever the laser lingers, the collagen cures and becomes solid.
Gradually, the object being printed is lowered and new layers are added. The printer can currently lay down collagen at a resolution of around 20 micrometers, but will need to achieve resolution of a micrometer in size to make the lung functional.
Once a collagen lung scaffold has been printed, the next step is to infuse it with human cells, a process called recellularization.
The goal here is to use stem cells that grow on scaffolding and differentiate, ultimately providing the proper functionality. Early evidence indicates this approach can work.
In 2018, Harvard University experimental surgeon Harald Ott reported that he pumped billions of human cells (from umbilical cords and diced lungs) into a pig lung stripped of its own cells. When Ott’s team reconnected it to a pig’s circulation, the resulting organ showed rudimentary function.
Humanizing Pig Lungs
Another of Rothblatt’s organ manufacturing strategies is called xenotransplantation, the idea of transplanting an animal’s organs into humans who need a replacement.
Given the fact that adult pig organs are similar in size and shape to those of humans, United Therapeutics has focused on genetically engineering pigs to allow humans to use their organs. “It’s actually not rocket science,” said Rothblatt in her 2015 TED talk. “It’s editing one gene after another.”
To accomplish this goal, United Therapeutics made a series of investments in companies such as Revivicor Inc. and Synthetic Genomics Inc., and signed large funding agreements with the University of Maryland, University of Alabama, and New York Presbyterian/Columbia University Medical Center to create xenotransplantation programs for new hearts, kidneys, and lungs, respectively. Rothblatt hopes to see human translation in three to four years.
In preparation for that day, United Therapeutics owns a 132-acre property in Research Triangle Park and built a 275,000-square-foot medical laboratory that will ultimately have the capability to annually produce up to 1,000 sets of healthy pig lungs—known as xenolungs—from genetically engineered pigs.
Lung Ex Vivo Perfusion Systems
Beyond 3D printing and genetically engineering pig lungs, Rothblatt has already begun implementing a third near-term approach to improve the supply of lungs across the US.
Only about 30 percent of potential donor lungs meet transplant criteria in the first place; of those, only about 85 percent of those are usable once they arrive at the surgery center. As a result, nearly 75 percent of possible lungs never make it to the recipient in need.
What if these lungs could be rejuvenated? This concept informs Dr. Rothblatt’s next approach.
In 2016, United Therapeutics invested $41.8 million in TransMedics Inc., an Andover, Massachusetts company that develops ex vivo perfusion systems for donor lungs, hearts, and kidneys.
The XVIVO Perfusion System takes marginal-quality lungs that initially failed to meet transplantation standard-of-care criteria and perfuses and ventilates them at normothermic conditions, providing an opportunity for surgeons to reassess transplant suitability.
Rejuvenate Young Blood and Parabiosis
In HBO’s parody of the Bay Area tech community, Silicon Valley, one of the episodes (Season 4, Episode 5) is named “The Blood Boy.”
In this installment, tech billionaire Gavin Belson (Matt Ross) is meeting with Richard Hendricks (Thomas Middleditch) and his team, speaking about the future of the decentralized internet. A young, muscled twenty-something disrupts the meeting when he rolls in a transfusion stand and silently hooks an intravenous connection between himself and Belson.
Belson then introduces the newcomer as his “transfusion associate” and begins to explain the science of parabiosis: “Regular transfusions of the blood of a younger physically fit donor can significantly retard the aging process.”
While the sitcom is fiction, that science has merit, and the scenario portrayed in the episode is already happening today.
On the first point, research at Stanford and Harvard has demonstrated that older animals, when transfused with the blood of young animals, experience regeneration across many tissues and organs.
The opposite is also true: young animals, when transfused with the blood of older animals, experience accelerated aging. But capitalizing on this virtual fountain of youth has been tricky.
One company, a San Francisco-based startup called Ambrosia, recently commenced one of the trials on parabiosis. Their protocol is simple: Healthy participants aged 35 and older get a transfusion of blood plasma from donors under 25, and researchers monitor their blood over the next two years for molecular indicators of health and aging.
Ambrosia’s founder Jesse Karmazin became interested in launching a company around parabiosis after seeing impressive data from animals and studies conducted abroad in humans: In one trial after another, subjects experience a reversal of aging symptoms across every major organ system. “The effects seem to be almost permanent,” he said. “It’s almost like there’s a resetting of gene expression.”
Infusing your own cord blood stem cells as you age may have tremendous longevity benefits. Following an FDA press release in February 2019, Ambrosia halted its consumer-facing treatment after several months of operation.
Understandably, the FDA raised concerns about the practice of parabiosis because to date, there is a marked lack of clinical data to support the treatment’s effectiveness.
On the other end of the reputability spectrum is a startup called Elevian, spun out of Harvard University. Elevian is approaching longevity with a careful, scientifically validated strategy. (Full Disclosure: I am both an advisor to and investor in Elevian.)
CEO Mark Allen, MD, is joined by a dozen MDs and Ph.Ds out of Harvard. Elevian’s scientific founders started the company after identifying specific circulating factors that may be responsible for the “young blood” effect.
One example: A naturally occurring molecule known as “growth differentiation factor 11,” or GDF11, when injected into aged mice, reproduces many of the regenerative effects of young blood, regenerating heart, brain, muscles, lungs, and kidneys.
More specifically, GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism.
Elevian is developing a number of therapeutics that regulate GDF11 and other circulating factors. The goal is to restore our body’s natural regenerative capacity, which Elevian believes can address some of the root causes of age-associated disease with the promise of reversing or preventing many aging-related diseases and extending the healthy lifespan.
In 1992, futurist Leland Kaiser coined the term “regenerative medicine”:
“A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.”
Since then, the powerful regenerative medicine industry has grown exponentially, and this rapid growth is anticipated to continue.
A dramatic extension of the human healthspan is just over the horizon. Soon, we’ll all have the regenerative superpowers previously relegated to a handful of animals and comic books.
What new opportunities open up when anybody, anywhere, and at anytime can regenerate, replenish, and replace entire organs and metabolic systems on command?
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