By Eve Herold – Editor-in-Chief, Healthspan Action Coalition –
Healthspan Action Coalition (HSAC): In a nutshell, what’s your vision for Accelerated Biosciences?
Yuta Lee (YL): We have a stem cell platform which consists of the earliest cells you can get without ethical issues. Our first priority is to cure diseases and then, in the future, to democratize stem cell therapies for prevention and longevity. We source our cells from the outer cell layer of embryos removed from ectopic pregnancies that are non-viable, and therefore uncontroversial. These cells, called trophoblasts, are pluripotent and can make 85 doublings, which could create 2 trillion human beings. So, the cells are already scalable.
HSAC: Can you explain how this avoids any ethical issues?
YL: We source our trophoblast stem cells from ectopic pregnancies, which happens when the embryo gets stuck in the fallopian tube instead of implanting in the mother’s uterus. This happens in about 2% of all pregnancies worldwide and the cause is unknown. This is always an emergency requiring surgery to remove the embryo from the tube, because otherwise the condition is life-threatening to the mother. Normally, the embryo with its trophoblastic cells is thrown away because it is non-viable. On one hand, we have to perform the surgery to save the mother, and on the second hand, the embryo is already non-viable. In addition, we are only taking the outer tissue of the embryo that later would become the placenta. This is the earliest time point to source tissue without actively destroying an embryo.
HSAC: Is there a danger that these cells could create tumors, as has happened with pluripotent cell transplants in animals and humans?
YL: The fear of using immortal cell lines such as embryonic stem cells or induced pluripotent stem cells (iPSCs) is that they may potentially turn into a tumor. Cancer cells are also immortal. With our trophoblast stem cells, there’s no cancer risk because the cells naturally senesce and are not immortal, but we can drive them out pretty far in terms of population doublings, which just means the cells can ‘double’ many times. We envision them as a highly versatile cellular ‘Nvidia chip’ that scientists can use to create cures for a large array of diseases. We are already working with over 40 research institutions for various diseases. In fact, we’re already providing exosomes to the beauty and cosmetic market. These super early exosomes can systemically down-regulate inflammation, which is very attractive as a key ingredient
HSAC: Lots of studies have shown Inflammation to be a major aspect of aging. Could these cells be used to create treatments that lower inflammation throughout the body to slow down aging?
YL: Yes, we’re currently working with the National Institute on Aging (NIA) to find ways to use these cells to slow or reverse aging. Chronic inflammation is a key driver of age-related diseases. The more inflammation we have in our bodies, the more likely age-related diseases will show up. Our goal is to reduce systemic inflammation using proteins coming from these trophoblast stem cells. These cells secrete beneficial proteins and exosomes that could be administered by IV to deliver anti-inflammatory effects throughout the body, potentially delaying disease and promoting healthy aging. This approach is inspired by parabiosis research done at top US universities over the last 3 decades, where proteins from young blood have shown systemic rejuvenation effects in older animals. Our long-term goal is to, first, cure aging-related diseases and then prove that we can use this therapy as a prevention to push our healthspan and longevity beyond 150 years old.
HSAC: What about the risk of immune rejection?
YL: First you have to ask, ‘how is it that a mother’s body doesn’t attack the baby she is carrying as alien?’ After all, the baby has different genes than the mother. It’s because the placental tissues, from which we derive our trophoblasts, are immune-privileged to prevent the body from rejecting the embryo. Unlike embryonic stem cells, our trophoblast stem cells express Human Leukocyte Antigen-G (HLA-G), which naturally suppresses immune reactions and minimizes the risk of rejection. This effect is so powerful that you can have a surrogate mother carry and deliver a baby that is not biologically related. We are harnessing this incredible function from human evolution to scale and democratize therapies for longevity. When we succeed, our vision is to make these advanced therapies available for everyone, no matter the socioeconomic circumstance. It is no longer only for the super-rich.
HSAC: So clearly the cells will need to be maintained in culture at the point of removal until they can be maintained long-term in the lab. How does the procedure work? Does AB partner with doctors, hospitals to safely harvest them?
YL: We partner with several hospitals in Taiwan to source the cells. Typically, a woman will show up at the emergency room with extreme pain. When the doctor diagnoses her with an unruptured ectopic pregnancy, an emergency surgery is needed called a salpingectomy. In this procedure, the surgeon ablates both sides of the ectopic mass and removes it with a scope; then they give the mass to a pathologist to confirm that it is an ectopic so that they can discard it as medical waste. It is well established that embryos from ectopic pregnancies are nonviable. In fact, religious philosophers also have the opinion that salpingectomies are morally acceptable to save the mother from potential death. We keep only the pre-placental tissues and isolate the trophoblast stem cells in our lab.
We have agreements with five different hospitals who call us when an ectopic pregnancy is going to be removed. To date, we already have 17 GMP compliant donor cells banked away for future use. GMP stands for ‘Good Manufacturing Practice” which is the highest quality designation for manufacturing of biological material that is used for human clinical trials and approved therapies. We have already manufactured one of those donor human trophoblast stem cells to a GMP master cell bank.
HSAC: When an embryo is removed during surgery, who owns the cells? Do the women give permission prior to the surgery?
YL: For a salpingectomy, removing a non-viable ectopic embryo, the control of the excised cells or the surgically removed cells rests with the hospital as medical waste. We have an Institutional Review Board approval for the protocol and we obtain donor consent prior to the surgery for the pre-placental tissue.
HSAC: So, you maintain a bank of the cells that can be shared with researchers working on specific diseases?
YL: Yes, one goal is to make their use widespread. Our policy is to collaborate with these cells with any research institution or company who wants to use them. Come one, come all. We believe our trophoblasts provide one of the most ideal starting stem cell sources possible, and we want to cure as many diseases as possible in the shortest possible time. I watched my parents both go through cancer and I’m 53, so I’m personally motivated to solve this problem. In ten years, I envision a future where hundreds of companies are advancing clinical trials using our trophoblast platform to address a wide range of diseases. For those of us over 50, this may represent a pivotal opportunity – one that could shape whether we live vibrantly to 150 and beyond, with our health and vitality fully intact.
HSAC: For years, beauty and cosmetic companies have been making claims about skin products containing stem cells, but the benefits so far have been extremely limited because they use plant stem cells, which can’t possibly have the same rejuvenating effect as human-derived cells. What are these companies doing with the AB cells?
YL: Plant and animal stem cells are considered xenogeneic, which means that they are from a foreign species and, thus, foreign to the human body. The research continues, but it is largely unknown what effects they really have and how it compares to human sources. Our trophoblast stem cells are from a human source. We’re already selling the exosomes derived from our cell lines to the beauty and cosmetics industry. We received a unique INCI (International Nomenclature Cosmetic Ingredient) name for Human Trophoblast Stem Cells, which is now an internationally recognized cosmetic ingredient for beauty and cosmetic companies. Our ingredient is currently strictly limited to topical use.
HSAC: Are your trophoblast cells immortal?
YL: No, our trophoblast stem cells are not immortal. They are naturally senescent cells, but they’re very young cells that will last a long time until they eventually become senescent and stop growing. They don’t divide indefinitely, and this is why they are unlikely to cause tumors, as opposed to immortal embryonic stem cells or induced pluripotent stem cells. These cells continuously grow and if undifferentiated, can potentially become a tumor. We’ve been working on this technology for more than 20 years, so the cells are well characterized. It so happens that my father, Professor Jau-nan Lee M.D. Ph.D., an OBGYN surgeon, discovered the cells in 2003. To avoid the ethical issues of using the embryos in research, he scraped off the pre-placental cells from the embryo and cultured them. Not only do we have an early allogeneic cell source, we now also have the most replete patent portfolio of any stem cell source.
HSAC: What is the difference between autologous and allogeneic cell sources? Can you explain it in the context of future therapies?
YL: For any cell therapy, you need a starting cell source. The cell source can be ‘autologous,’ which means it comes from your own body and therefore are a perfect genetic match. You can then use the cells to create a therapy and put it back into your own body. Autologous therapies do not have rejection issues because they are from your own body; but they are hard to scale because the therapy needs to be manufactured from the patient’s own cells. In another words, every therapy is manufactured specifically only for you. That makes autologous therapies very expensive—one of the biggest downsides.
On the other end, the cell source can be ‘allogeneic,’ which means it comes from a healthy donor. Just the opposite from autologous, allogeneic therapies can be scaled with mass manufacturing to be given to every patient walking into the doctor’s office; but you have to overcome the immune rejection issue since donor cells will be seen as foreign by your immune system. Since our trophoblast cells have natural immune privilege, we now have the holy grail of an allogeneic cell source that has scale and natural immune privilege. This now gives us the opportunity to bypass the immune rejection issue, manufacture in scale and drive down the cost of cell therapies. We have done 5 animal studies with our human trophoblast stem cells on animals with complete immune systems. Not only did our cells not alert the animal immune system, they regenerate the organs we are targeting without growing tumors or teratomas. We are excited to move forward to see these cells in human trials in the near future.
HSAC: It’s very exciting to see stem cell research advancing to the stage where stem cell treatments seem to be just around the corner. Do you have any closing thoughts about how to move the field forward in addition to using these ethically sourced, immune-privileged, scalable cells?
YL: I think we really need to grasp the reality that we are actually quite close to reaching Longevity Escape Velocity (LEV), which Dr. Aubrey de Grey defines as a time when “advancements in rejuvenation therapies and interventions outpace the rate of aging itself.” When we reach this, almost everyone can continue living in good health indefinitely. To accelerate to LEV, we have to come together as a supportive community, recognizing the incredible opportunity before us with ethically sourced, immune-privileged, and scalable stem cells. By uniting our efforts and focusing on our shared goal, we can accelerate our progress toward greater longevity and healthier lives for all. Collaboration and encouragement will help realize the promise of stem cell research for the benefit of humanity. For those of us above the age of 50, I will say “Hang in there. Be hopeful. Be healthy. Invest in longevity projects. We are almost there.”
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