Cell Therapy “101”
Real information to support real healthcare decisions
Most digital visitors to Hope Biosciences Research Foundation (HBRF) arrive by very personal motivation — either they or a loved one are likely living with a degenerative disease or illness without palatable or effective treatment options. Digital seekers of information often report being made aware of cell therapy through a personal testimonial of some kind, but are unlikely to be familiar with the terms and language used most commonly in scientific papers, videos, or other resources they might find in the quest to learn more. Evaluating the vast array of information at our online fingertips is crucial to determining whether participation in a clinical trial or expanded access protocol at HBRF, or anywhere else, is the best choice for you and your family. To that end, here begins part one of a multi-segment dialogue meant to help you reduce stress and optimize discernment, so you can make clear, confident decisions. We begin by answering a question about the most oft-used term in the field:
What is cell therapy?!
Cell therapy is a form of regenerative medicine. The term “regenerative medicine” refers to scientific efforts to restore diseased or injured tissues or organs, supporting the body in its natural processes whenever and to the greatest extent possible, rather than implanting devices or engineered parts that may require years of stringent pharmaceutical support before ultimately failing.[1] [2] HBRF exists to accelerate translational work in regenerative medicine in a variety of forms. (Bonus term! “Translational” means scientific studies that are “translated” from the laboratory or animal studies into humans. Lab and animal studies are often focused on figuring out how stuff works and why it does; these are also called “mechanistic” studies. Translational research determines whether what we see at work in the lab or in animal studies, “translates” the way scientists think it will in humans. Translational work done well is strongly patient-focused, and people are where HBRF’s heart lies.)
“Cell therapy” refers specifically to the practice of transferring cellular material into a person for medical purposes.[3] Cell therapies vary in cell types; methods of derivation; methods of transfer; and amount and type of work undertaken in a laboratory setting, if any, to grow or alter cells prior to returning them to the human they are intended to support. Many opinions exist about the merits and potential pitfalls of every combination of factors. Today, much work in cell therapy involves human stem cells. Stem cells are an unspecialized type of cell that can transform into a variety of specialized cell types in the body. For example, a stem cell might be capable of becoming a liver cell, brain cell, heart cell, and so on, if exposed to the necessary stimuli and conditions. Stem cells also have potential to divide for an indefinite period, which means they can make many copies of both themselves and differentiated cells. Stem cells “work” by realizing their potential and becoming other cell types when, where, and as needed by the body, making them particularly promising in complex conditions that affect multiple bodily symptoms, like many degenerative diseases or traumatic injuries. HBRF is equipped and ready to conduct research in a variety of adult cell types.
To date, HBRF has and is conducting FDA-authorized research using mesenchymal stem cells (MSCs).[4] MSCs are multipotent adult stem cells[5] capable of making many other types of tissue cells and contributing to physiological processes in myriad ways. MSCs can differentiate into various local cell types at injured sites, secrete growth factors that help in tissue regeneration, produce new secretory pathways at a cellular level, and effectively communicate with stressed or injured somatic cells to transfer their cytoplasmic elements and organelles.[6] MSCs are also capable of penetrating the blood brain barrier,[7] and are increasingly explored as a vehicle for gene therapy.[8] Several studies have revealed that in addition to their ability to differentiate into different cell types, MSCs may also exert therapeutic effects through cell “enhancement,” which generally means the production and release of trophic and anti-inflammatory factors whose therapeutic effects may help to restore the body’s natural physiological environment. Furthermore, MSCs have a function in the modulation of the inflammatory and immunological responses in the body. Introduction of stem cells can also stimulate continued regeneration. MSCs also have a documented homing ability; that is, they migrate to injured tissues in areas the body tells the stem cells are in need, whether that need is apparent on anything larger than a cellular level yet or not. Tactically, this homing ability means that MSC therapy can simply introduce cells into the body through intravenous infusion, a minimally invasive process and one ideally accessible to medically fragile patients, and trust the cells to end up where and as needed.[9] MSC research has been conducted for at least 50 years. If you “Google” something along the lines of “who invented cell therapy,” prepare for a debate — Robert Hooke discovered cells as the building block of the human body in 1655; in the early 1900’s, various scientists throughout the world started illustrating diagrams and publishing papers validating the existence of stem cells; Donnall Thomas won the Nobel Prize for a successful bone marrow transplant performed in 1957; and A.J. Friedenstein and his team are generally credited with identification of mesenchymal stem cells (MCSs) in 1976, though Russian research Alexander Maximow first referred to this type of cell as early as the 1920s. Our point is simply — MSC therapy has an established and accepted safety profile.
Other cell types carry promise, however, and HBRF looks forward to expanding the research portfolio in the years ahead. The central questions of regeneration are logistical — how many cells, at what interval, over what period of time, are required to reverse degeneration? It stands to reason that developing a plethora of answers will best serve the American population as a whole, and that is what HBRF exists to do.
With any cell type, a patient can receive their own cells, called “autologous” treatment, or someone else’s cells, known as “allogeneic.” Researchers hypothesize that the medical benefits of receiving stem cells in either case might be similar, at least in the initial stages of treatment. Donor cell therapy treatments can also be given without immunosuppressant drugs to promote acceptance. Immunosuppressant drugs are required in organ or tissue transplants because the surface membrane of every cell contains glycoproteins that trigger, in the loosest sense, an immune response when threats to the cell are detected. Because stem cells have not yet become anything, the body does not necessarily see new stem cells as a threat. At the time of this writing, HBRF is actively enrolling participants in allogeneic studies in Parkinson’s Disease and “Long Haul” COVID, having recently completed autologous studies in both conditions. A growing suite of allogeneic research represents what HBRF hopes is a significant contribution in increasing regulatory acceptance of allogeneic adult cell therapies. Allogeneic therapies, with their dramatically reduced costs for manufacturing stem cells to a comparable safety profile as autologous cell therapies, and with equal or better potential for scalability, represent a promising way for ensuring equitable access to cell therapies in the future.
Be mindful in your own research: most reputable scientific work with stem cells involves removing cells, growing or altering them, and returning cells to the body in either increased quantity or entirely different state, which takes time. While there is a fair amount of orthopedic work that can be undertaken in a single day, and recent research that promises to shorten the manufacturing time for certain types of cell-based cancer therapies to less than one day in animal models,[10] the key marketing hook of fly-by-night stem cell “clinics” is the boast that health can be achieved with one administration, in one day, of their product or procedure. These shady sidewalk shops tarnish the reputation of cell therapy to the detriment of legitimate work in the field, and negatively impact the financial well-being, and possibly the health, of sick or injured people seeking help. Advertisements for questionable practices are often found on television in infomercial or paid-testimonial format, or in newspapers or magazines; ads typically detail removal of source material from one part of the body, to be spun down or distilled, then injected into a different place in the body to promote site-specific healing. These procedures are akin to cosmetic surgery, and none the more therapeutic.[11]
A bonus “be mindful in your own research” point: HBRF does not see cell therapy as at odds with established therapeutics, nor should any research entity exploring questions with the patient’s well-being and best interests at the heart of their inquiry. Cell therapies may be complimentary to cancer treatments, for instance, perhaps having roles in the delivery of therapeutics and in mitigation of side effects. Cell therapy is also not necessarily at odds with biomaterials work, to cite another example. A future of widely accepted partnership between disciplines is exciting to contemplate, and may lead us to somewhere we all want to go — a healthcare landscape that includes straight-forward, appropriately regulated access to cell therapy, supported by medical insurance carriers, right here in the United States.
[1] See Chris Mason and Peter Dunnill’s opinion editorial “A Brief Definition of Regenerative Medicine” in Regenerative Medicine, 2008 (3)1, 1–5.
[2] Mao AS, Mooney DJ. Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14452–9. doi: 10.1073/pnas.1508520112. PMID: 26598661; PMCID: PMC4664309.
[3] El-Kadiry AE, Rafei M, Shammaa R. Cell Therapy: Types, Regulation, and Clinical Benefits. Front Med (Lausanne). 2021 Nov 22;8:756029. doi: 10.3389/fmed.2021.756029. PMID: 34881261; PMCID: PMC8645794.
[4] Debate continues over which words best describe MSCs, whose functions mechanistic researchers continue to learn about. Common monikers include “Mesenchymal Stem Cell,” “Mesenchymal Stromal Cell,” and “Medicinal Signaling Cell.” HBSCRF holds “mesenchymal stem cells” to be defensible and accurate.
[5] Academic debate persists surrounding the technical status of MSCs as “pluripotent” or “multipotent.” As of this writing, academia tends to use “multipotent,” while semi-popular and popular writing trends toward use of “pluripotent.” We will use the term “multipotent” for this conversation, though arguing the terminology is not of great concern for this conversation — the capabilities of the stem cells remain as they are, no matter how we categorize them at this juncture in scientific discovery.
[6] N. Attia, et al., “Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects,” Pharmaceutics 13, no.6 (2021): 843. https://doi.org/10.3390/pharmaceutics13060843
[7] A. Weiss & M.H. Dahlke, “Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs,” Frontiers in immunology 10 (2019): 1191. https://doi.org/10.3389/fimmu.2019.01191
[8] Attia, “Mesenchymal Stem Cells,” 843.
[9] S. Kim, et al., “The Preventive Therapeutic Effects of Intravenous Human Adipose-Derived Stem Cells in Alzheimer’s Disease Mice,” (2012). https://doi.org/10.1371/journal.pone.0045757
[10] See “Penn Researchers Shorten Manufacturing for CAR T Cell Therapy” in Penn Medicine News, March 29, 2022, pennmedicine.org.
[11] Debate continues to rage in regenerative medicine around definition of the word “manipulation,” because biologics that are considered “more than minimally manipulated” fall under the same level of FDA regulation as untested pharmaceuticals. Simply moving tissues and whatever stem cells may be in there from one place to another is not considered “manipulation,” and is therefore an unregulated practice.
