Lizards can grow whole limbs. Flatworms, starfish, and sea cucumbers grow whole bodies. Sharks are constantly replacing lost teeth, often growing over 20,000 teeth over a lifetime. How to transfer these practical superpowers to people? Answer: through cutting edge regenerative medicine innovation. While big data and artificial intelligence are changing our medical practice and inventing new therapies, regenerative medicine aims to replace and rejuvenate our physical body.
Can all organs of the human body be renewed?
Three regenerative technologies are currently being developed that together should enable us to completely and completely improve and even replace vital human organs:
- Recovery: stem cells, the body's regenerative engine
- Replacement: organ regeneration and bioprinting
- Rejuvenation: young blood and parabiosis
Let's dive into the perspective of immortality.
Renewal and stem cells: the body's regenerative engine
Stem cells are undecided cells that can transform into specialized cells - heart, neurons, liver, lungs, skin, and so on. They can also divide to produce more stem cells.
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A child or a young adult has many of these stem cells and they act as a built-in recovery system. They are often called on to the site of injury or inflammation to repair and restore normal function.
But with age, our stock of stem cells begins to decrease by a factor of 100 - 10,000, depending on tissue and organs. In addition, stem cells undergo genetic mutations that reduce the quality and efficiency of your body's renewal and repair.
Think of stem cells as a team of repairmen in your newly built mansion. When the mansion is new and the repairmen are young, it won't be difficult to fix anything. But as the repairmen age and the number of them dwindles, your mansion gradually declines and finally collapses.
What if we could repair and rejuvenate the stem cell population?
One option for recovery and rejuvenation is to extract and concentrate your own autologous adult stem cells from places such as adipose (or adipose) tissue or bone bridge.
These stem cells, however, are fewer in number and have undergone mutations (depending on your age) when compared to the original "source code". Many scientists and doctors now prefer an alternative source: obtaining stem cells from the placenta or umbilical cord left over after childbirth. These stem cells, available in large numbers and containing the newborn's intact software, can be injected into joints or intravenously for rejuvenation and revitalization.
Think of these stem cells as chemical factories that produce vital growth factors that can help reduce inflammation, fight autoimmune diseases, increase muscle mass, repair joints, and even revitalize skin and regrow hair.
Over the past ten years, the number of stem cell-related research publications has increased 40 times a year, and the stem cell market is expected to grow to $ 297 billion by 2022.
Growing initiatives in the research and development of treatment options for chronic diseases and the growing demand for regenerative treatment options are the most significant driving forces behind this emerging industry.
Biologists led by Koji Nishida of Osaka University in Japan have discovered a new way of growing and developing the tissues that make up the human eyeball. Scientists can grow the retina, cornea, lens of the eye and more using just a small sample of adult skin.
In a Stanford study, seven of eighteen stroke survivors who agreed to stem cell treatment showed significant improvements in motor function. This treatment may work for other neurodegenerative diseases such as Alzheimer's, Parkinson's and ALS.
Doctors at the USC Neurorehabilitation Center injected stem cells into the injured cervical spine of a recently paralyzed 21-year-old man. Three months later, he showed significant improvement in sensitivity and movement in both hands.
In 2019, doctors in the UK cured an HIV patient for the second time in history, thanks to the effectiveness of stem cells. After allogeneic hematopoietic stem cell treatment of a cancer patient (with HIV) with Hodgkin's lymphoma, the patient began a long-term remission of HIV - 18 months, which continued at the time of publication of the study.
Replacement: organ regeneration and 3D printing
In January 2019, in the US alone, more than 113,000 people were waiting for an organ transplant queue - and every 10 minutes someone is added to that queue.
A huge number of people in need of "spare parts" never make it to the waiting lists. And an average of 20 people die every day while waiting for a transplant. The organs are sorely lacking.
Excessive demand for organ donations will only increase as technology - like self-driving cars - makes the world a safer place. And many organ donors are the unfortunate consequence of car and motorcycle accidents. Safer vehicles mean fewer accidents and donors.
Obviously, substitutional and restorative (regenerative) medicine presents a huge opportunity here.
Organ dealers
United Therapeutics CEO Martin Rothblatt, a former aerospace entrepreneur (she was the founder of Sirius Satellite Radio), changed careers in the 1990s after her daughter developed a rare lung disease.
Today she works in the organ replacement industry. Initially, Rothblatt focused on lung disease while working on a replacement lung. To achieve this goal, her company, United Therapeutics, was working on several technologies in parallel.
3D printing lungs
In 2017, United teamed up with one of the world's largest 3D printing companies - 3D Systems - to create a collagen bioprinter and paid another company, 3Scan, to slice up the lungs and create a detailed map of their insides.
The 3D Systems bioprinter now uses the stereolithography method. An ultraviolet laser illuminates a small pool of collagen doped with light-sensitive molecules. Wherever the laser stops, collagen solidifies.
Gradually the printed object is overgrown with new layers. The printer can currently stack collagen at a resolution of about 20 micrometers, but a micrometer-scale resolution will be required to ensure lung function.
After the collagen scaffolds of the lungs are printed, the next step is to inject human cells into them - the so-called process of recellularization. The goal here is to use stem cells that grow on the scaffold and differentiate, ultimately providing proper functionality. All indications are that this approach might work.
In 2018, an experimental surgeon at Harvard University, Harald Ott, reported that he had pumped billions of human cells (from the umbilical cord and chopped lungs) into a pig's lung, devoid of its own cells. When Ott's team reconnected the organ to the pig's circulation, it manifested rudimentary function.
Humanizing pig lungs
Another Rothblatt organ production strategy is called xenotransplantation, the idea of transplanting an animal's organs into humans who need replacement.
Given that the organs of an adult pig are similar in size and shape to humans, United Therapeutics has focused on genetically modifying pigs to allow humans to use their organs. “It's not really that big of a deal,” Rothblatt said in 2015. "It's editing one gene after another."
To achieve this goal, United Therapeutics has made a number of investments in companies such as Revivicor and Synthetic Genomics, and has signed major funding agreements with the University of Maryland, University of Alabama and New York Presbyterian / Columbia Medical Center to create new heart, kidney and lung xenotransplant programs. respectively. Rothblatt hopes to see the first human transplant in three to four years.
In preparation for the day, United Therapeutics acquired 132 acres of land in Research Triangle Park and built a 140,000 square meter medical laboratory that will eventually produce up to 1,000 healthy pig lungs - xenolungs - from genetically modified pigs annually.
Ex vivo lung perfusion systems
In addition to 3D printing and genetic engineering of pig lungs, Rothblatt has already launched a third short-term approach to improve lung delivery to those in need.
Only about 30 percent of potential donor lungs meet the transplant criteria; of these, only 85% can be used after arrival at the surgical center. As a result, almost 75% of possible lungs never end up in a recipient in need.
What if these lungs could be repaired? This is precisely what Dr. Rothblatt's next approach is.
In 2016, United Therapeutics invested $ 41.8 million in TransMedics, a Massachusetts-based company that develops ex vivo perfusion systems for donated lungs, hearts and kidneys.
XVIVO Perfusion System takes lungs of marginal quality that did not initially meet the criteria for transplantation, performs perfusion and ventilation under normal thermal conditions, so that surgeons can re-evaluate the suitability of the graft.
Young blood and parabiosis
What is parabiosis? It is believed that regular blood transfusions of younger, physically fit individuals can significantly slow down the aging process. And this is already happening now.
Studies by Stanford and Harvard have shown that older animals, when transfused with the blood of young animals, demonstrate regeneration in many tissues and organs.
The converse is also true: young animals age faster when they receive blood from older animals. Capitalizing on this virtual fountain of youth is tricky.
Ambrosia
One company, a San Francisco-based startup called Ambrosia, recently began practical trials of parabiosis. Their protocol is simple: healthy participants age 35 and older receive plasma transfusions from donors under the age of 25, and scientists monitor their blood over the next two years, trying to determine molecular indicators of health and aging.
Ambrosia founder Jesse Karmazin became interested in starting a parabiosis company after seeing impressive animal data and human studies abroad: in each trial, subjects experienced reversal of aging symptoms in nearly all major organ systems. "The effects seem to be almost permanent," he says. "It's almost like restoring gene expression."
Introducing your own cord blood stem cells as you age can have tremendous benefits for longevity. Following an FDA press release in February 2019, Ambrosia stopped treating clients a few months after starting operations.
It is understood that the FDA has raised concerns about the practice of parabiosis because to date there is a marked lack of clinical data to support the effectiveness of the treatment.
Elevian
At the other end of the reputation spectrum is Elevian, a startup from Harvard University. Elevian approaches longevity with a careful, science-based strategy. Peter Diamandis became both an advisor and an investor at Elevian.
Company CEO Mark Allen, M. D., has joined a dozen PhDs from Harvard. Elevian's scientific founders joined 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. After its introduction to elderly mice, many of the regenerative effects of young blood were reproduced, the heart, brain, muscles, lungs and kidneys were regenerated.
In particular, GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle recovery, improves exercise tolerance, improves brain function and cerebral blood flow, and improves metabolism.
Elevian is developing a range of therapeutic agents that regulate GDF11 and other circulating factors. The goal is to restore the body's natural ability to regenerate, which Elevian believes can address a number of the underlying causes of age-related diseases and reverse or prevent many of the diseases associated with aging and extend healthy lifespan.
Are we approaching immortality?
In 1992, the futurist Leland Kaiser coined the term "regenerative medicine":
"A new branch of medicine will evolve that will try to change the course of chronic disease and in many cases will repair tired and weakened organ systems."
Since then, the powerful regenerative medicine industry has grown exponentially, and this rapid growth is expected to continue. A radical extension of human life is on the horizon. Very soon, we will all be gaining regenerative superpowers that previously belonged to only a handful of animals and superheroes from comics.
Ilya Khel