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Life is like the changing of seasons, each uniquely beautiful. Just as autumn leaves fall to the ground and make way for winter’s gentle snow, life has transformational cycles. The cycle of life continues through the changing seasons, like how the autumn winds strip the trees of their leaves and help them prepare for the challenges of the coming winter. Similarly, life tests us by placing challenges of disease, injury, and aging complexities in our paths.

William Haseltine
William Haseltine

Nonetheless, just as spring comes around again, so does the cycle of renewal in life. The natural regenerative abilities of our bodies kick in, much like the first thaw of spring that signals new life for plants and animals. Regenerative medicine harnesses this natural ability of our bodies to heal by helping to restore damaged tissues and improve the quality of life.

From cell therapies to gene editing to biomechanical interventions, regenerative medicine holds promise in transforming healthcare as we know it. Just as the seasons bring forth new beginnings, regenerative medicine ushers in a new era of hope for those who need healing.

Personalized medicine through DNA technologies

DNA is at the core of regenerative medicine. It serves as a blueprint and a building block for the human body. DNA’s smaller units connect to create the iconic double helix shape, which contains the instructions for creating and maintaining our bodies. The study of genetics focuses on DNA and has allowed us to understand the fundamental processes that govern growth, development, and disease response.

Mutations in specific genes cause many inherited diseases like beta-thalassemia, sickle cell anemia, and cystic fibrosis. Recently, gene editing technologies such as CRISPR were developed to replace defective genes with healthy ones. This has led to numerous clinical trials and promises to eradicate genetic illnesses in the future. Researchers and physicians have also leveraged this knowledge to develop novel antibodies that fight infectious diseases and cancers.

DNA technologies have revolutionized the pharmaceutical and drug discovery industries, with the demand for DNA-based drugs expected to reach over $113 million by 2029. The need for DNA repair drugs is also likely to generate market value of close to $20 million by 2026.

The transformative power of DNA technologies goes beyond pharmaceuticals and drug discovery. The combination of DNA technologies and regenerative medicine has ushered in a new era of personalized medicine, in which an individual’s genetic makeup can be used as the foundation for targeted therapy.

The application of DNA technologies to antibodies has revolutionized medicine, in turn transforming biomedical sciences and the pharmaceutical industry. Gone are the days of relying solely on small-molecule chemicals, with new technologies driving the production of high-value products. Antibody therapies like Herceptin, Avastin, Rituxan, Erbitux, Gertrude, Opdivo, and Tecentriq are now commonly prescribed for cancer, rheumatoid arthritis, Crohn’s disease, and macular degeneration.

By precisely targeting and neutralizing antigens, antibody medications emulate the body’s immune response to combat diseases with unparalleled accuracy. Thus, they offer a more targeted and precise approach to improve patient outcomes.

Regenerative medicine as effective cancer treatments

Cancer is a prominent contributor to global mortality, claiming nearly 10 million lives in 2020 alone. There are over 200 types of cancer and the disease can affect any body part. It occurs when cells undergo uncontrolled growth and division to form benign or malignant tumors. It is important to note that certain types of cancer, like blood cancer, can cause harm without tumors.

Cancer treatment has seen significant improvements in recent years thanks to the synergies between various treatment modalities of regenerative medicine. Traditional treatment methods such as chemotherapy and radiation therapy often have severe side effects and can negatively impact healthy cells. However, regenerative medicine therapies such as cell-based therapies and immunotherapies have emerged as more targeted and effective alternatives.

One of the earliest breakthroughs in cancer treatment dates back to 1891, when William B. Coley, MD, developed a basic form of immunotherapy collectively known as “Coley’s toxins.” The treatment involved injecting patients with bacteria to eliminate cancer cells. In 1963, the FDA approved anew drubased on these principles.

By 1970, researchers had developed a modified version of these toxins, known as mixed bacterial vaccines, for treating bone and soft-tissue sarcomas. However, the effectiveness of this treatment was short-lived due to the emergence of natural killer cells, monoclonal antibodies, and checkpoint inhibitors.

An infographic showing the different types of antibodies.
FIGURE 1: An infographic showing the different types of antibodies.
ACCESS Health International – Monoclonal Antibodies: The Once and Future Cure for Covid-19 by William Haseltine and Griffin McCombs

Natural killer cells, also called NK cells, are a type of white blood cell that can identify and destroy cancer cells. When performing the first bone marrow transplants for leukemia treatment, doctors were unaware they were utilizing NK cells. In 2005, NK cell-mediated immunotherapy was officially recognized as a safe and effective treatment. Since then, the focus has been on optimizing the source of NK cells and enhancing their cell-killing abilities.

The discovery of monoclonal antibodies came on the heels of the discovery of NK cells. The therapeutic application of monoclonal antibodies emerged in 1975. These targeted agents specifically recognize and bind to antigens on the surface of cancer cells. Among the various types of antibodies tested as cancer therapeutics, IgG monoclonal antibodies have proven the most successful.

Antibody therapies currently reign supreme among treatments and have soared in popularity, topping sales charts. With over 100 FDA-approved antibody-based medications, biologics account for 20% of newly approved drugs every year. The 2022 monoclonal antibody market topped $186.6 billion, with an expected value of $609 billion by 2032. These antibodies are also employed for treating COVID-19, aiding the battle against the virus that changed the world in 2020.

Another breakthrough came in the form of checkpoint inhibitors. These therapies unlock the immune system’s potential by blocking molecules that inhibit immune cells. By releasing these brakes, T cells can identify and combat tumors. The first approved checkpoint inhibitor therapy, ipilimumab, received FDA approval in 2011 for melanoma treatment.

Another innovative therapy that uses the immune system is chimeric antigen receptor T-cell (CAR T) therapy, which involves modifying T cells to effectively identify and combat cancer cells. Several therapies have gained FDA approval for treating blood cancers, showing remarkable efficacy in clinical trials. Ongoing studies are investigating a combination of checkpoint inhibitors, CAR T, and chemotherapy treatments and exploring potential synergies between these treatment modalities.

An infographic showing the process of CAR T therapy.
FIGURE 2: An infographic showing the process of CAR T therapy.
ACCESS Health International – The Future of Medicine: Healing Yourself: Regenerative Medicine | Part One
by William Haseltine

Since 2017, the FDA has approved a half dozen CAR T therapies for different blood cancers. CAR T has become an essential component of modern cancer treatment. Clinical trials have yielded promising results, with many patients enjoying long-term remission after receiving CAR T treatments.

Innovations in CAR T treatments are still expanding. One example is the CAR T switch. The idea is to create an antibody switch that controls CAR T cells. This tunable response may overcome a key translational barrier of CAR T-cell therapy. Early studies in mice show that these switchable CAR T cells may be safer for patients.

Stem cells and induced pluripotent stem cells: a source of endless possibilities

T cells are just one of the approximately 200 cell types in the human body. There are around 37 trillion cells in the human body, of which about 330 billion are replaced daily. This means that over 3.8 million cells are created in our body every second. Cellular medicine or cell therapy uses this regeneration potential to aid healing.

Cell therapy aims to restore health by replacing damaged or diseased cells with vibrant, healthy ones. This cutting-edge method involves intricate processes like regulating cellular function through direct interaction and leveraging the immune system to eliminate disease-causing cells. Currently, cells are modified in vitro to regenerate specific tissues and serve as the building blocks of restoration.

To first step of this transformative process is to identify a suitable source of cells, usually versatile stem cells. These extraordinary cells can differentiate into various cell types given optimal conditions and surroundings. Through this intricate differentiation process, stem cells undergo remarkable changes in size, shape, metabolic activity, and functionality. This ability paves the way for healing and rejuvenation. A notable advantage of stem cells is their autologous or patient-matched nature as they can be derived from the patient’s body. This dramatically reduces the risk of immune rejection.

Cellular medicine relies on various stem cell sources like embryonic stem cells, adult stem cells, and induced pluripotent stem cells (iPSCs). The discovery of iPSCs in 2006 brought exciting possibilities for therapeutics and biomedical research. iPSCs are generated by introducing specific transcription factors, called Yamanka factors, to a given cell type. Creating iPSCs entails four steps: isolating and culturing donor cells, converting them into stem cells via reprogramming”, cultivating and harvesting them, and ultimately obtaining the desired iPSCs.

An infographic showing the process of creating IPSCs.
FIGURE 3: An infographic showing the process of creating IPSCs.
ACCESS Health International

Stem cells and iPSCs are tools that researchers use to create better disease models. They can create cells with the specific disease-related mutations by reprogramming cells from patients with genetic diseases. Researchers can then force these cells to differentiate into a specific cell type to study disease mechanisms and the effectiveness of targeted therapies. These advances have raised questions of whether we can use this method to grow entire tissues and organs.

Disease modeling and drug development with organoids

Organoids are structures composed of stem cells that replicate the properties of specific tissues or organs. By mimicking the characteristics of human organs, organoids provide crucial insights into disease progression, drug development, and organ development. They are typically formed through self-assembly, using iPSCs or primary tissue samples.

Organoids are a better alternative to traditional two-dimensional culture systems. They accurately replicate in vivo organ physiology and enable efficient disease modeling. For example, organoids mimic neurodegenerative processes in conditions like Alzheimer’s and Parkinson’s disease. These faithful reproductions provide insights into disease progression and aid in developing mitigation strategies.

Significant progress has been made in generating organoids that mimic various organs, like the brain, kidney, lung, intestine, stomach, liver, pancreas, thyroid, and retina. This has created new opportunities for exploring organ-specific diseases. Researchers from the Eindhoven University of Technology have made a significant breakthrough in growing functional kidney organoids. They developed a groundbreaking method of growing kidney organoids with active glomeruli, which are crucial for waste filtration. This achievement is a significant step towards realizing fully functional kidney organoids.

Scientists from Harvard University have also made progress by replicating the intricate helical pattern of the human heart at a microscopic level. They generated functional heart organoids demonstrating spontaneous contractions similar to those observed in a natural heart. This development has immense potential for developing treatments for heart-related ailments.

Additionally, researchers are working on creating eye and brain organoids, which hold promise for treating eye-related conditions like macular degeneration and studying the development and function of the human brain. These organoids can also help model neurodevelopmental disorders such as autism and schizophrenia. Collaborative efforts between various research groups promise to deepen our understanding of these issues and pave the way for innovative treatments and therapies.

The promise and challenges of transplantation and xenotransplantation

Organ transplantation is a medical procedure that has been around for less than a century. It involves surgically transplanting an organ from one person to another. The first successful organ transplant was performed in 1954, when Joseph Murray, MD, conducted a kidney transplant between identical twin brothers. Since then, organ transplants have become a standard treatment for end-stage organ failure, saving countless lives and improving the quality of life for patients worldwide.

A major development in organ transplantation has been the development of immunosuppressive drugs, which help prevent the body from rejecting a transplanted organ. These drugs have allowed people to receive transplants from donors who are not a perfect match, greatly expanding the pool of potential donors. Recent advances in tissue engineering have allowed scientists to grow organoid in the lab using a patient’s own cells.

Despite these advances, organ transplantation faces many challenges. One major hurdle is the need for more donor organs, which has led to long waitlists and difficult decisions about who should receive a transplant. To address these issues, scientists have been studying the possibility of xenotransplantation. Thanks to genetic alterations in pigs, it is now possible to produce organs that are more compatible with humans. These genetically modified pig organs have already been used in successful heart and kidney transplants.

Researchers at New York University also conducted a successful xenotransplantation procedure in 2022. They transplanted a genetically modified pig kidney into a brain-dead patient. The kidney functioned normally and was not rejected by the body, marking a significant step towards addressing the global organ shortage.

Despite challenges such as endogenous retroviruses in pig DNA and the inability of the immune system to accept foreign animal tissues, advances in gene editing and biomaterials offer hope for transforming the field of organ transplantation. Continued research and advances in this field may lead to more successful and widespread use of xenotransplantation.

Infographic illustrating the organoid development process.
FIGURE 4: Infographic illustrating the organoid development process.
ACCESS Health International – The Future of Medicine: Healing Yourself: Regenerative Medicine | Part One
by William Haseltine

Brain-machine interfaces and the future of regenerative medicine

Healthcare innovations have continued beyond CAR-T and xenotransplants. Recent discoveries include brain-machine interfaces (BMIs) that facilitate direct communication between the brain and external devices like computers or prosthetics. These interfaces can restore function and movement to individuals with neurological disorders or injuries. For instance, BMIs are being developed to record and interpret brain activity signals, thus helping paralyzed individuals communicate through computers.

One promising bioimplant is the PeriCord, which promotes tissue revascularization and improves cardiac function in heart attack patients with damaged heart tissue. Biomechanical prosthetics offer unprecedented possibilities for individuals who have undergone limb amputation due to complications from diabetic foot ulceration.

With many individuals poised to benefit from these advanced robotic prosthetics, it is no surprise that the global market is forecasted to skyrocket to over $2.8 billion in the next decade. Beyond BMIs, technology continues to reshape regenerative medicine in captivating ways. One fascinating area of innovation involves leveraging the vagus nerve to address a range of conditions like inflammatory diseases, depression, and epilepsy.

The vagus nerve, a critical connection between the brain and body, regulates many different bodily functions. By using electrical impulses to stimulate the vagus nerve, we can address conditions like depression, epilepsy, and gastroparesis. Vagal nerve stimulation has been approved by the FDA for treating epilepsy, depression, and anxiety disorders.

A recent study published in PNAS suggests that vagus nerve stimulation may be effective for treating chronic inflammatory conditions like rheumatoid arthritis and Crohn’s disease as well. However, further clinical trials are needed to explore its potential as a treatment option. Understanding the vagus nerve’s various roles can bring us closer to new therapeutic targets.

Regenerative medicine has seen countless innovations. Cellular medicine was the starting point, but more discoveries and developments are required. Advances like biomaterials, organoids, gene therapies, and BMIs promise to transform medical diagnoses and treatments, and improve healthcare efficiency and accessibility. The future holds even more promise.


William R. Haseltine, PhD, is chair and president of the think tank ACCESS Health
International, a former Harvard Medical School and School of Public Health
professor and founder of the university’s cancer and HIV/AIDS research
departments. He is also the founder of more than a dozen biotechnology
companies, including Human Genome Sciences.

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