Regenerative medicine has come a long way, baby
The field of regenerative medicine had a shaky start. In 2002, when news spread about the first cloned animal, Dolly the sheep, a raucous debate ensued. Scary headlines and organized opposition groups put pressure on government leaders, who responded by tightening restrictions on this type of research.
Fast forward to today, and regenerative medicine, which focuses on making unhealthy tissues and organs healthy again, is rewriting the code to healing many disorders, though it’s still young enough to be considered nascent. What started as one of the most controversial areas in medicine is now promising to transform it.
Progress in the lab has addressed previous concerns. Back in the early 2000s, some of the most fervent controversy centered around somatic cell nuclear transfer (SCNT), the process used by scientists to produce Dolly. There was fear that this technique could be used in humans, with possibly adverse effects, considering the many medical problems of the animals who had been cloned.
But today, scientists have discovered better approaches with fewer risks. Pioneers in the field are embracing new possibilities for cellular reprogramming, 3D organ printing, AI collaboration, and even growing organs in space. It could bring a new era of personalized medicine for longer, healthier lives - while potentially sparking new controversies.
Engineering tissues from amniotic fluids
Work in regenerative medicine seeks to reverse damage to organs and tissues by culling, modifying and replacing cells in the human body. Scientists in this field reach deep into the mechanisms of diseases and the breakdowns of cells, the little workhorses that perform all life-giving processes. If cells can’t do their jobs, they take whole organs and systems down with them. Regenerative medicine seeks to harness the power of healthy cells derived from stem cells to do the work that can literally restore patients to a state of health—by giving them healthy, functioning tissues and organs.
Modern-day regenerative medicine takes its origin from the 1998 isolation of human embryonic stem cells, first achieved by John Gearhart at Johns Hopkins University. Gearhart isolated the pluripotent cells that can differentiate into virtually every kind of cell in the human body. There was a raging controversy about the use of these cells in research because at that time they came exclusively from early-stage embryos or fetal tissue.
Back then, the highly controversial SCNT cells were the only way to produce genetically matched stem cells to treat patients. Since then, the picture has changed radically because other sources of highly versatile stem cells have been developed. Today, scientists can derive stem cells from amniotic fluid or reprogram patients’ skin cells back to an immature state, so they can differentiate into whatever types of cells the patient needs.
In the context of medical history, the field of regenerative medicine is progressing at a dizzying speed. But for those living with aggressive or chronic illnesses, it can seem that the wheels of medical progress grind slowly.
The ethical debate has been dialed back and, in the last few decades, the field has produced important innovations, spurring the development of whole new FDA processes and categories, says Anthony Atala, a bioengineer and director of the Wake Forest Institute for Regenerative Medicine. Atala and a large team of researchers have pioneered many of the first applications of 3D printed tissues and organs using cells developed from patients or those obtained from amniotic fluid or placentas.
His lab, considered to be the largest devoted to translational regenerative medicine, is currently working with 40 different engineered human tissues. Sixteen of them have been transplanted into patients. That includes skin, bladders, urethras, muscles, kidneys and vaginal organs, to name just a few.
These achievements are made possible by converging disciplines and technologies, such as cell therapies, bioengineering, gene editing, nanotechnology and 3D printing, to create living tissues and organs for human transplants. Atala is currently overseeing clinical trials to test the safety of tissues and organs engineered in the Wake Forest lab, a significant step toward FDA approval.
In the context of medical history, the field of regenerative medicine is progressing at a dizzying speed. But for those living with aggressive or chronic illnesses, it can seem that the wheels of medical progress grind slowly.
“It’s never fast enough,” Atala says. “We want to get new treatments into the clinic faster, but the reality is that you have to dot all your i’s and cross all your t’s—and rightly so, for the sake of patient safety. People want predictions, but you can never predict how much work it will take to go from conceptualization to utilization.”
As a surgeon, he also treats patients and is able to follow transplant recipients. “At the end of the day, the goal is to get these technologies into patients, and working with the patients is a very rewarding experience,” he says. Will the 3D printed organs ever outrun the shortage of donated organs? “That’s the hope,” Atala says, “but this technology won’t eliminate the need for them in our lifetime.”
New methods are out of this world
Jeanne Loring, another pioneer in the field and director of the Center for Regenerative Medicine at Scripps Research Institute in San Diego, says that investment in regenerative medicine is not only paying off, but is leading to truly personalized medicine, one of the holy grails of modern science.
This is because a patient’s own skin cells can be reprogrammed to become replacements for various malfunctioning cells causing incurable diseases, such as diabetes, heart disease, macular degeneration and Parkinson’s. If the cells are obtained from a source other than the patient, they can be rejected by the immune system. This means that patients need lifelong immunosuppression, which isn’t ideal. “With Covid,” says Loring, “I became acutely aware of the dangers of immunosuppression.” Using the patient’s own cells eliminates that problem.
Microgravity conditions make it easier for the cells to form three-dimensional structures, which could more easily lead to the growing of whole organs. In fact, Loring's own cells have been sent to the ISS for study.
Loring has a special interest in neurons, or brain cells that can be developed by manipulating cells found in the skin. She is looking to eventually treat Parkinson’s disease using them. The manipulated cells produce dopamine, the critical hormone or neurotransmitter lacking in the brains of patients. A company she founded plans to start a Phase I clinical trial using cell therapies for Parkinson’s soon, she says.
This is the culmination of many years of basic research on her part, some of it on her own cells. In 2007, Loring had her own cells reprogrammed, so there’s a cell line that carries her DNA. “They’re just like embryonic stem cells, but personal,” she said.
Loring has another special interest—sending immature cells into space to be studied at the International Space Station. There, microgravity conditions make it easier for the cells to form three-dimensional structures, which could more easily lead to the growing of whole organs. In fact, her own cells have been sent to the ISS for study. “My colleagues and I have completed four missions at the space station,” she says. “The last cells came down last August. They were my own cells reprogrammed into pluripotent cells in 2009. No one else can say that,” she adds.
Future controversies and tipping points
Although the original SCNT debate has calmed down, more controversies may arise, Loring thinks.
One of them could concern growing synthetic embryos. The embryos are ultimately derived from embryonic stem cells, and it’s not clear to what stage these embryos can or will be grown in an artificial uterus—another recent invention. The science, so far done only in animals, is still new and has not been widely publicized but, eventually, “People will notice the production of synthetic embryos and growing them in an artificial uterus,” Loring says. It’s likely to incite many of the same reactions as the use of embryonic stem cells.
Bernard Siegel, the founder and director of the Regenerative Medicine Foundation and executive director of the newly formed Healthspan Action Coalition (HSAC), believes that stem cell science is rapidly approaching tipping point and changing all of medical science. (For disclosure, I do consulting work for HSAC). Siegel says that regenerative medicine has become a new pillar of medicine that has recently been fast-tracked by new technology.
Artificial intelligence is speeding up discoveries and the convergence of key disciplines, as demonstrated in Atala’s lab, which is creating complex new medical products that replace the body’s natural parts. Just as importantly, those parts are genetically matched and pose no risk of rejection.
These new technologies must be regulated, which can be a challenge, Siegel notes. “Cell therapies represent a challenge to the existing regulatory structure, including payment, reimbursement and infrastructure issues that 20 years ago, didn’t exist.” Now the FDA and other agencies are faced with this revolution, and they’re just beginning to adapt.
Siegel cited the 2021 FDA Modernization Act as a major step. The Act allows drug developers to use alternatives to animal testing in investigating the safety and efficacy of new compounds, loosening the agency’s requirement for extensive animal testing before a new drug can move into clinical trials. The Act is a recognition of the profound effect that cultured human cells are having on research. Being able to test drugs using actual human cells promises to be far safer and more accurate in predicting how they will act in the human body, and could accelerate drug development.
Siegel, a longtime veteran and founding father of several health advocacy organizations, believes this work helped bring cell therapies to people sooner rather than later. His new focus, through the HSAC, is to leverage regenerative medicine into extending not just the lifespan but the worldwide human healthspan, the period of life lived with health and vigor. “When you look at the HSAC as a tree,” asks Siegel, “what are the roots of that tree? Stem cell science and the huge ecosystem it has created.” The study of human aging is another root to the tree that has potential to lengthen healthspans.
The revolutionary science underlying the extension of the healthspan needs to be available to the whole world, Siegel says. “We need to take all these roots and come up with a way to improve the life of all mankind,” he says. “Everyone should be able to take advantage of this promising new world.”
When Erika Schreder’s 14-year-old daughter, who is Black, had her curly hair braided at a Seattle-area salon two or three times recently, the hairdresser applied a styling gel to seal the tresses in place.
Schreder and her daughter had been trying to avoid harmful chemicals, so they were shocked to later learn that this particular gel had the highest level of formaldehyde of any product tested by the Washington State Departments of Ecology and Health. In January 2023, the agencies released a report that uncovered high levels of formaldehyde in certain hair products, creams and lotions marketed to or used by people of color. When Schreder saw the report, she mentioned it to her daughter, who told her the name of the gel smoothed on her hair.
“It was really upsetting,” said Schreder, science director at Toxic-Free Future, a Seattle-based nonprofit environmental health research and advocacy organization. “Learning that this product used on my daughter’s hair contained cancer-causing formaldehyde made me even more committed to advocating for our state to ban toxic ingredients in cosmetics and personal care products.”
In 2013, Toxic-Free Future launched Mind the Store to challenge the nation’s largest retailers in adopting comprehensive policies that eliminate toxic chemicals in their personal care products and packaging, and develop safer alternatives.
Now, more efforts are underway to expose and mitigate the harm in cosmetics, hair care and other products that children apply on their faces, heads, nails and other body parts. Advocates hope to raise awareness among parents while prompting manufacturers and salon professionals to adopt safer alternatives.
A recent study by researchers at Columbia University Mailman School of Public Health and Earthjustice, a San Francisco-based nonprofit public interest environmental law organization, revealed that most children in the United States use makeup and body products that may contain carcinogens and other toxic chemicals. In January, the results were published in the International Journal of Environmental Research and Public Health. Based on more than 200 surveys, 70 percent of parents in the study reported that their children 12 or younger have used makeup and body products marketed to youth — for instance, glitter, face paint and lip gloss.
Childhood exposure to harmful makeup and body product ingredients can also be considered an environmental justice issue, as communities of color may be more likely to use these products.
“We are concerned about exposure to chemicals that may be found in cosmetics and body products, including those that are marketed toward children,” said the study’s senior author, Julie Herbstman, a professor and director of the Columbia Center for Children's Environmental Health. The goal of the survey was to try to understand how much kids are using cosmetic and body products and when, how and why they are using them.
“There is widespread use of children’s cosmetic and body products, and kids are using them principally to play,” Herbstman said. “That’s really quite different than how adults use cosmetic and body products.” Even with products that are specifically designed for children, “there’s no regulation that ensures that these products are safe for kids.” Also, she said, some children are using adult products — and they may do so in inadvisable ways, such as ingesting lipstick or applying it to other areas of the face.
Earlier research demonstrated that beauty and personal care products manufactured for children and adults frequently contain toxic chemicals, such as lead, asbestos, PFAS, phthalates and formaldehyde. Heavy metals and other toxic chemicals in children’s makeup and body products are particularly harmful to infants and youth, who are growing rapidly and whose bodies are less efficient at metabolizing these chemicals. Whether these chemicals are added intentionally or are present as contaminants, they have been associated with cancer, neurodevelopmental harm, and other serious and irreversible health effects, the Columbia University and Earthjustice researchers noted.
“Even when concentrations of individual chemicals are low in products, the potential for interactive effects from multiple toxicants is important to take into consideration,” the authors wrote in the journal article. “Allergic reactions, such as contact dermatitis, are some of the most frequently cited negative health outcomes associated with the use of cosmetics.”
Children’s small body side, rapid growth rate and immature immune systems are biologically more prone to the effects of toxicants than adults.
Adobe Stock
In addition to children’s rapid growth rate, the study also reported that their small body size, developing tissues and organs, and immature immune systems are biologically more prone to the effects of toxicants than adults. Meanwhile, the study noted, “childhood exposure to harmful makeup and body product ingredients can also be considered an environmental justice issue, as communities of color may be more likely to use these products.”
Although adults are the typical users of cosmetics, similar items are heavily marketed to youth with attention-grabbing features such as bright colors, animals and cartoon characters, according to the study. Beyond conventional makeup such as eyeshadow and lipstick, children may apply face paint, body glitter, nail polish, hair gel and fragrances. They also may frequent social media platforms on which these products are increasingly being promoted.
Products for both children and adults are currently regulated by the U.S. Food and Drug Administration under the Federal Food, Drug, and Cosmetic Act of 1938. Also, the Fair Packaging and Labeling Act of 1967 directs the Federal Trade Commission and the FDA “to issue regulations requiring that all ‘consumer commodities’ be labeled to disclose net contents, identity of commodity, and name and place of business of the product's manufacturer, packer, or distributor.” As the Columbia University and Earthjustice authors pointed out, though, “current safety regulations have been widely criticized as inadequate.”
The Personal Care Products Council in Washington, D.C., “fundamentally disagrees with the premise that companies put toxic chemicals in products produced for children,” industry spokeswoman Lisa Powers said in an email. Founded in 1894, the national trade association represents 600 member companies that manufacture, distribute and supply most personal care products marketed in the United States.
No category of consumer products is subject to less government oversight than cosmetics and other personal care products. -- Environmental Working Group.
“Science and safety are the cornerstones of our industry,” Powers stated. For more than a decade, she wrote, “the [Council] and our member companies worked diligently with a bipartisan group of congressional leaders and a diverse group of stakeholders to enhance the effectiveness of the FDA regulatory authority and to provide the safety reassurances that consumers expect and deserve.”
Powers added that the “industry employs and consults thousands of scientific and medical experts” who study the impacts of cosmetics and personal care products and the ingredients used in them. The Council also maintains a comprehensive database where consumers can look up science and safety information on the thousands of ingredients in sunscreens, toothpaste, shampoo, moisturizer, makeup, fragrances and other products.
However, the Environmental Working Group, which empowers consumers with breakthrough research to make informed choices about healthy living, believes the regulations are still not robust enough. “No category of consumer products is subject to less government oversight than cosmetics and other personal care products,” states the organization’s website. “Although many of the chemicals and contaminants in cosmetics and personal care products likely pose little risk, exposure to some has been linked to serious health problems, including cancer.”
The group, which operates the Skin Deep Database noted that “since 2009, 595 cosmetics manufacturers have reported using 88 chemicals, in more than 73,000 products, that have been linked to cancer, birth defects or reproductive harm.”
But change, for both adults and kids, is on the horizon. The Modernization of Cosmetics Regulation Act of 2022 significantly expanded the FDA’s authority to regulate cosmetics. In May 2023, Washington state adopted a law regulating cosmetics and personal care products. The Toxic-Free Cosmetics Act (HB 1047) bans chemicals in beauty and personal care products, such as PFAS, lead, mercury, phthalates and formaldehyde-releasing agents. These bans take effect in 2025, except for formaldehyde releasers, which have a phased-in approach starting in 2026.
Industry and advocates view this as a positive development. Powers, the spokesperson, praised “the long-awaited” Modernization Cosmetics Regulation Act of 2022, which she said, “advances product safety and innovation.” Jen Lee, chief impact officer at Beautycoutner, a company that sells personal care products, also welcomes the change. “We were proud to support the Washington Toxic-Free Cosmetics Act (HB 1047) by mobilizing our community of Brand Advocates who reside in Washington State,” Lee said. “Together, they made their voices heard by sending over 1,000 emails to their state legislators urging them to support and pass the bill.”
Laurie Valeriano, executive director of Toxic-Free Future, praised the upcoming Washington state law as “a huge win for public health and the environment that will have impacts that ripple across the nation.” She added that “companies won’t make special products for Washington state.” Instead, “they will reformulate and make products safer for everyone” — adults and children.
You shouldn’t have to be a toxicologist to shop for shampoo. -- Washington State Rep. Sharlett Mena
The new legislation will require Washington state agencies to assess the hazards of chemicals used in products that can impact vulnerable populations, while providing support for small businesses and independent cosmetologists to transition to safer products.
The Toxic-Free Future team lauds the Cosmetics Act, signed in May 2023.
Courtesy Toxic-Free Future
“When we go to a store, we assume the products on the shelf are safe, but this isn’t always true,” said Washington State Rep. Sharlett Mena, a Democrat serving in the 29th Legislative District (Tacoma), who sponsored the law. “I introduced this bill (HB 1047) because currently, the burden is on the consumer to navigate labels and find safe alternatives. You shouldn’t have to be a toxicologist to shop for shampoo.”
The new law aims to protect people of all ages, but especially youth. “Children are more susceptible to the impacts of toxic chemicals because their bodies are still developing,” Mena said. “Lead, for example, is significantly more hazardous to children than adults. Also, since children, unlike adults, tend to put things in their mouths all the time, they are more exposed to harmful chemicals in personal care and other products.”
Cosmetologists and hair professionals are taking notice. “Safety should be the practitioner’s number one concern” in using products on small children, said Anwar Saleem, a hair stylist, instructor and former salon owner in Washington, D.C., who is chairman of the D.C. Board of Barbering and Cosmetology and president of the National Interstate Council of State Boards of Cosmetology. “There are so many products on the market that it can be confusing.”
Hair products designed and labeled for children's use often have milder formulations, but “every child is unique, and what works for one may not work for another,” Saleem said. He recommends doing a patch test, in which the stylist or cosmetologist dabs the product on a small, inconspicuous area of the scalp or skin and waits anywhere from an hour to a day to check for irritation before continuing to serve the client. “Performing a patch test, observing children's reactions to a product and adequately adjusting are essential.”
Saleem seeks products that are free from harsh chemicals such as sulfates, phthalates and parabens, noting that these ingredients can be irritating and drying to the hair and scalp. If a child has sensitive skin or allergies, Saleem opts for hypoallergenic products.
We also need to ensure that less toxic alternatives are available and accessible to all consumers. It’s often under-resourced, low-income populations who suffer the burden of environmental exposures and do not have access or cannot afford these safer alternatives. -- Lesliam Quirós-Alcalá.
Lesliam Quirós-Alcalá, an assistant professor in the department of environmental health and engineering at the Johns Hopkins Bloomberg School of Public Health, said current regulatory loopholes on product labeling still allow manufacturers to advertise their cosmetics and personal care products as “gentle” and “natural.” However, she said, those terms may be misleading as they don’t necessarily mean the contents are less toxic or harmful to consumers.
“We also need to ensure that less toxic alternatives are available and accessible to all consumers,” Quirós-Alcalá said, “as often alternatives considered to be less toxic come with a hefty price tag.” As a result, “it’s often under-resourced, low-income populations who suffer the burden of environmental exposures and do not have access or cannot afford these safer alternatives.”
To advocate for safer alternatives, Quirós-Alcalá suggests that parents turn to consumer groups involved in publicizing the harms of personal care products. The Campaign for Safe Cosmetics is a program of Breast Cancer Prevention Partners, a national science-based advocacy organization aiming to prevent the disease by eliminating related environmental exposures. Other resources that inform users about unsafe ingredients include the mobile apps Clearya and Think Dirty.
“Children are not little adults, so it’s important to increase parent and consumer awareness to minimize their exposures to toxic chemicals in everyday products,” Quirós-Alcalá said. “Becoming smarter, more knowledgeable consumers is the first step to protecting your family from potentially harmful and toxic ingredients in consumer products.”
A startup aims to make medicines in space
Story by Big Think
On June 12, a SpaceX Falcon 9 rocket deployed 72 small satellites for customers — including the world’s first space factory.
The challenge: In 2019, pharma giant Merck revealed that an experiment on the International Space Station had shown how to make its blockbuster cancer drug Keytruda more stable. That meant it could now be administered via a shot rather than through an IV infusion.
The key to the discovery was the fact that particles behave differently when freed from the force of gravity — seeing how its drug crystalized in microgravity helped Merck figure out how to tweak its manufacturing process on Earth to produce the more stable version.
Microgravity research could potentially lead to many more discoveries like this one, or even the development of brand-new drugs, but ISS astronauts only have so much time for commercial experiments.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth.”-- Will Bruey.
The only options for accessing microgravity (or free fall) outside of orbit, meanwhile, are parabolic airplane flights and drop towers, and those are only useful for experiments that require less than a minute in microgravity — Merck’s ISS experiment took 18 days.
The idea: In 2021, California startup Varda Space Industries announced its intention to build the world’s first space factory, to manufacture not only pharmaceuticals but other products that could benefit from being made in microgravity, such as semiconductors and fiber optic cables.
This factory would consist of a commercial satellite platform attached to two Varda-made modules. One module would contain equipment capable of autonomously manufacturing a product. The other would be a reentry capsule to bring the finished goods back to Earth.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth,” said CEO Will Bruey, who’d previously developed and flown spacecraft for SpaceX.
“We have a team stacked with aerospace talent in the prime of their careers, focused on getting working hardware to orbit as quickly as possible,” he continued.
“[Pharmaceuticals] are the most valuable chemicals per unit mass. And they also have a large market on Earth.” -- Will Bruey, CEO of Varda Space.
What’s new? At the time, Varda said it planned to launch its first space factory in 2023, and, in what feels like a first for a space startup, it has actually hit that ambitious launch schedule.
“We have ACQUISITION OF SIGNAL,” the startup tweeted soon after the Falcon 9 launch on June 12. “The world’s first space factory’s solar panels have found the sun and it’s beginning to de-tumble.”
During the satellite’s first week in space, Varda will focus on testing its systems to make sure everything works as hoped. The second week will be dedicated to heating and cooling the old HIV-AIDS drug ritonavir repeatedly to study how its particles crystalize in microgravity.
After about a month in space, Varda will attempt to bring its first space factory back to Earth, sending it through the atmosphere at hypersonic speeds and then using a parachute system to safely land at the Department of Defense’s Utah Test and Training Range.
Looking ahead: Ultimately, Varda’s space factories could end up serving dual purposes as manufacturing facilities and hypersonic testbeds — the Air Force has already awarded the startup a contract to use its next reentry capsule to test hardware for hypersonic missiles.
But as for manufacturing other types of goods, Varda plans to stick with drugs for now.
“[Pharmaceuticals] are the most valuable chemicals per unit mass,” Bruey told CNN. “And they also have a large market on Earth.”
“You’re not going to see Varda do anything other than pharmaceuticals for the next minimum of six, seven years,” added Delian Asparouhov, Varda’s co-founder and president.