Stem Cell Therapies: The Era of Regenerative Medicine?

MEDICINE THAT WAS once seen only in science-fiction fantasy is gradually becoming a reality. Tracheas have been generated in laboratories and successfully implanted in humans for several years. In clinical trials around the world, advances are being made against various diseases, including retinitis pigmentosa,¹ severe combined immunodeficiency (SCID)² and age-related macular degeneration.³ There are hopeful signs that patients may one day prevail against these now-debilitating conditions. On other fronts, multiple sclerosis patients treated with stem cells are showing remarkable results as well,⁴ and stroke and traumatic brain injury victims are beginning to gain a bit of the functionality they lost after their injuries.⁵

Thanks to stem cell research and therapies, all of these marvelous results are within our reach — and much more progress is expected in coming years within this still somewhat fledgling industry.

Advances in this field, however, require considerably more research and funding, and more often than not, both are limited. Debates about the ethics and proper use of stem cell therapies, meanwhile, abound.

A Revolutionary Treatment

It’s no wonder disagreements exist among researchers, academics and physicians regarding regenerative medicine. Stem cell therapies are an entirely different ideology from anything used before, and protocols and methodologies are still being developed. With biologics and more traditional medical procedures, doctors are essentially trying to “patch up” harm done by a disease or a traumatic injury to ease symptoms — not wholly cure the illness or regenerate tissue itself. With stem cell therapies, however, the paradigm shifts to tissue restoration as the primary goal. In diseases such as cystic fibrosis, for example, physicians hope to eventually restore lung tissue within diseased lungs,⁶ not merely rein in a patient’s symptoms or try to keep a damaged lung functioning. The goal is to develop therapies to a point where physicians and researchers don’t merely stop a disease from progressing, but actually turn back time in a sense and renew an organ so a patient has improved or even complete use of it.

The Basics of the Field

A bit of context lays the scaffolding for further discussion. First, at a most basic level, stem cells are crucial, unspecialized cells within every person’s body. Capable of self-renewal (not merely duplication) and differentiation into other types of cells, stem cells continually repair and maintain all tissues in the body. Without them, we might live only a few hours because our other cells would have nothing to replenish them. When we exercise, for example, the microscopic tears made in our muscles are healed by stem cells, a process that gradually increases the muscle’s strength as we exercise over time. Stem cells are, in fact, continually doing this type of healing in every tissue of a person’s body. It’s that type of regenerative power that doctors and researchers seek to harness and enhance to apply to diseased and wounded tissue. Our bodies are already reasonably effective at healing themselves in many cases, but researchers strive to focus and accelerate the process.⁷

It’s their self-renewal and differentiation abilities that make stem cells so exciting to the medical field. Beyond these two features, various types of stem cells have different abilities. Embryonic cells, for example, are pluripotent (capable of becoming virtually any type of cell), while adult cells are multipotent (still capable of some differentiation, but more limited). Induced pluripotent stem cells (iPS) are relatively new and very exciting to researchers because they are reprogrammed adult cells that have already been differentiated into a specific cell. Once they are reprogrammed in a lab, iPS cells have virtually the same ability as embryonic cells to be pluripotent. Which cells are used for treatment in clinical trials depends largely on a patient’s needs.⁸

In some cases, stem cells come autologously from a patient’s own body, and in others, a donor offers allogeneic transplant. Increasingly, multipotent adult cells are used autologously, taken from a patient’s own bone marrow, fat, skin, blood and even teeth. Once drawn through autologous or allogeneic means, stem cells are then enriched by methods as simple as centrifugation or cultivation through petri dishes and agar. The resulting product is then injected, infused or surgically transplanted into a patient’s body at the site of disease or injury.⁷

Two Schools of Thought

Dr. Kristin Comella, chief scientific officer and board member of U.S. Stem Cell, Sunrise, Fla., says there are two groups of scientists advancing stem cell therapy today. In one camp are the academic researchers, and in the other, the physicians who want to bring stem cell therapies directly to clinics without so much regulation. Comella claims the latter camp. “The university scientists,” she explains, are “those who are very interested in doing extensive research and want a lot of animal testing before any stem cell therapy becomes mainstream and is brought to humans. But we want to bring stem cell therapy directly to clinics, using it through physicians rather than going through pharmaceutical companies. I want these therapies to be considered similar to surgeries or medical procedures as opposed to drugs in the hands of pharmaceutical companies.”

“There’s a debate right now about the safest and the best way to bring stem cell therapies forward,” adds Dr. Comella. “In our camp, we say: ‘We shouldn’t withhold these therapies from patients. Patients have a right to use their own tissue and use their own bodies’ potential to heal them of diseases, especially diseases that have no other [treatment] option.’ We see these patients’ fear and illness and realize that, without using experimental stem cell therapies, there is little to nothing we can do to help them. We believe patients who are otherwise given a death sentence have a right to try an experimental procedure. And, they can provide informed consent and do it.”

Kevin McCormack, senior director for public communications and patient advocate outreach at California Institute for Regenerative Medicine (CIRM), a stem cell research funding organization, explains: “The FDA [U.S. Food and Drug Administration] has very clear guidelines about what it considers a medicine or a treatment. And that is, if you take stem cells from someone, that usually involves taking some fat, putting it through a centrifuge to isolate the stem cells and then reintroducing those cells into them — say their knee to help repair damage. The FDA says that is something ‘minimally manipulated’ and allowable if the procedure is done at the same time. If, on the other hand, you take those same stem cells, isolate them through a centrifuge, and I return a week or so later to receive them somewhere other than my knee, then the FDA would say that’s not the same procedure, so therefore it certainly counts as something inappropriate and unallowable. The FDA’s rules are a little bit gray, which is why clinics have popped up all over the country offering all types of therapies that are unproven and unlicensed. So there’s some confusion there. In terms of CIRM’s standards, absolutely, we believe that stem cells are something that need to be regulated and thoroughly tested in a way that ensures the safety of patients, which is always our prime concern.”

However, adds McCormack, “The FDA evolved regulating biologics, and stem cell therapies are an entirely new field. The FDA’s rules haven’t evolved at the same rate as medical development has, so they’re trying to make the old system fit an entirely new paradigm, and it’s not a good fit. That’s why we think there needs to be reconsideration. There needs to be a re-evaluation of how this can best be done.”

Current Uses and Research

Despite the excitement regarding clinical trials of stem cell therapies, it’s crucial to remember that FDA has not yet approved any stem cell-based products for use beyond “cord blood-derived hematopoietic progenitor cells (blood-forming stem cells) for certain indications.”⁸ But current research truly is promising and exciting.

For example, as alluded to earlier, Canadian doctors Harold Atkins, a bone marrow transplant specialist, and Mark Freedman, a neurologist, were very aggressive in a clinical trial that involved killing multiple sclerosis patients’ damaged immune systems with chemotherapy, then injecting modified autologous stem cells to “reboot” their bodies. The Lancet reports that the treatment “halted clinical relapses and development of new brain lesions in 23 of 24 patients with multiple sclerosis,” and “eight of the 23 [remaining] patients had sustained improvement in their disability over 7.5 years.”⁴

Besides this, University of California, Los Angeles stem cell researcher Dr. Don Kohn has cured 18 SCID children by removing stem cells from their bone marrow, genetically modifying them to correct the defect and reintroducing them to the children’s bodies.²

And Dr. Damien Bates, chief medical officer and head of research at SanBio, Inc., says he is pleased with the findings from a recent clinical study on stroke and traumatic brain injury patients. Dubbed a Phase I/IIa clinical study, the dose escalation trial involved 12 subjects from Stanford University and six from the University of Pittsburg Medical Center.⁵ The most-improved patients who regained impressive functionality overnight after receiving stem cell injections in their brains were interviewed on several news programs. The media quickly proclaimed the results “miraculous.” Cautiously, however, Dr. Bates says, “I am excited that some patients have improved dramatically, but I think we all need to be careful not to overstate any claim at this stage; we’ve got a long way to go with these additional studies that are much more rigorous, and then mandated by the FDA, before we can make any definitive conclusions about the efficacy of the product.”

It’s important to note that Dr. Bates is not the only cautiously optimistic researcher. In his blog “The Niche,” University of California, Davis stem cell scientist Paul Knoepfler, PhD, writes: “Stem cells are not a cure-all. I am as excited as anybody about the potential of stem cells to treat a whole bunch of diseases and injuries, but they are not some kind of miracle cure for everything.”⁹

Dr. Comella has a different perspective entirely on research, however, because she is rarely able to do it. “To do large double blind placebo-controlled trials to determine whether or not these are safe and effective treatments for patients requires quite a bit of funding,” explains Dr. Comella. “As an example, to do 100 patient trials would cost $10 million, and the FDA requires, typically, thousands of patients, which could cost hundreds of millions of dollars to bring these therapies forward in the traditional drug-approval process. Really, the only people who can afford those trials are big pharmaceutical companies. In this case, where physicians are getting stem cells from the patients themselves, there’s no drug to patent, there’s no drug to bottle, so Big Pharma is not going to be interested in paying for these clinical trials. As a result, there’s no funding for us to do the clinical trials, and we’re caught in a catch-22. Yes, I would love to do clinical trials to demonstrate that these therapies work, but I don’t have the funding to do it, and Big Pharma’s not going to do it because there’s no product for them to sell at the end.”

Ethical Questions

Embryonic and fetal tissues have been used in science for decades, yet many people remain uncomfortable with that fact for religious or moral beliefs. Induced pluripotent stem cells, of course, have the potential to lessen the ethical concern. It remains to be seen, though, whether iPS will be a long-term viable option that can completely replace embryonic cells. Still, the issue may be at least somewhat resolved since Dr. Robin Smith, president of the Stem for Life Foundation, says that, though early stem cell researchers believed embryonic tissue was the most effective, science has since proved otherwise. She adds that today there are more than 5,000 clinical trials using adult stem cells and fewer than 50 using embryonic cells.¹⁰

And, at a 2015 stem cell conference at the Vatican, at which CIRM president and CEO Randy Mills was invited to attend, the Pope himself expressed his belief that stem cell research is crucial to saving lives. Though the Catholic Church condemns use of embryonic stem cells, it upholds the belief that stem cell research is morally upright when using adult cells.¹¹

Future Possibilities

Dr. Comella holds nothing back when she envisions stem cell therapies of the future: “I see a combination of all the different types of regenerative medicine, so cell and gene therapies combined, also incorporating stem cell therapies with any surgical procedures. One day, we might even be able to eliminate many surgical procedures. Many knee replacements that are happening today could be unnecessary because, in the future, we’ll be able to just repair the tissue. Certainly, any arthroscopic surgeries on the knee will become outdated very rapidly. [Clinical data] is already indicating that the long-term effects of such surgeries are not good. We don’t have to cut such tissue out. Leave it in. Repair it. That can be applied to not just orthopedics, but many different indications.

“We are doing a lot of these things right now, so the future of medicine is here. We’re treating neurological disorders and getting some amazing results. We’re treating orthopedic problems, autoimmune problems, different degenerative diseases. By placing stem cell therapy in the hands of physicians who are actually seeing the patients, and doing this day in and day out with patients, we can move rapidly into cures for patients.”

Dr. Bates holds an equally optimistic view: “I think the future of stem cell therapy is really exciting, and I’ve basically devoted my life to it. I’m a plastic and reconstructive surgeon, so my whole life I’ve been involved with wound repair and tissue healing. Trying to understand the biology behind why some animals can regenerate entire limbs and eyes and we humans can’t is fascinating. I think stem cells are the one potential avenue to try and trigger that regenerative potential that we have. I did my PhD in embryology, and we know that up to the third trimester, fetuses have the ability to, not regenerate entire limbs, but heal their wounds with no scarring, which is just phenomenal. Why do we lose that potential as we get older? We don’t fully understand that, but if we can tap into that regenerative potential and heal our tissues so we can produce functional tissue without scarring, then that’s amazing. I think that’s the Holy Grail, and I think that most companies, including SanBio, are working toward that. Whether stem cells arethe definite answer remains to be seen, but stem cells are an area of huge focus by a lot of different companies at the moment.”