• Feature

    The Role of PTs in Regenerative Medicine

    Physical therapists are playing a key role in the rehabilitation of patients who undergo regenerative procedures such as stem cell therapy and platelet-rich plasma injections.

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    Kristin Bowne, PT, DPT, MS, clearly remembers the day in 2011 when she received the email that changed her career.

    "It was an invitation to the First Annual Symposium on Regenerative Rehabilitation at the University of Pittsburgh," she notes. The symposium, the message explained, would explore the emerging role of physical therapy in regenerative medicine, a field that focuses on treatment interventions including stem cell therapy and bio-scaffolding to repair, replace, or regenerate impaired or nonfunctional human tissue.

    "I'd been in orthopedics and sports medicine for more than 20 years, and it just so happened that when I got that email I was thinking about what to do next—how my career might evolve," Bowne says. "So, I flew out to Pennsylvania and went to the conference. It was so intriguing and exciting! I knew I'd found it. This was the future, and I wanted to be part of it."

    Fast-forward 5 years. Bowne's growing outpatient private practice, Kristin Bowne Physical Therapy in Scotts Valley, California, bills itself as "the premier rehabilitation clinic for emerging regenerative therapies," and as a center for clinical research into the field's newest methods.

    Her business "still is a general orthopedic, community-based practice," Bowne notes, but each year she sees more and more patients and clients who come to her office immediately after having undergone regenerative procedures to address ailments such as joint pain, osteoarthritis (OA), and annular tears (rips in the tough exterior of an intervertebral disc). "Often, they're opting for these procedures as an alternative to joint-replacement surgery," she explains. "They'll get the procedure done, then come in to start rehab the very next day."

    One recent patient, for example, arrived at Bowne's clinic less than 24 hours after having received an injection to his knee consisting of autologous bone marrow aspirate concentrate (BMAC) combined with platelet-rich plasma (PRP). Another patient—a former professional tennis player—had just been given stem cell injections to treat advanced OA in his knees and hips.

    For these patients and others like them, "you definitely have to take a different approach" from that taken with a typical patient, Bowne says. "First, we always try to see them before the procedure, if possible, to clear up their biomechanics and train them in exercises that will help them prepare. It's also important to maintain an open line of communication with their regenerative physicians. You also need to understand molecular biology, the science behind these procedures, and how different treatments affect healing times and the healing process."

    In the years Bowne has worked with individuals who have undergone regenerative therapy, she has developed her own regenerative rehabilitation program. It combines appropriate rest, biomechanical loading, tissue mobilization, and a number of procedure-specific protocols designed to guide patients through the recovery process and ultimately help them regain function. Now, she says, she's spending part of her time teaching these principles and therapeutic techniques to other physical therapists (PTs) around the country (including, notably, members of the physical therapy department at the Mayo Clinic in Rochester, Minnesota).

    "Here's the problem," Bowne says. "The consensus is that rehab is vital to success" after regenerative interventions such as PRP and stem cell transplantation, "but many physicians—understandably, I think—still are very cautious regarding to whom they'll send their patients after these procedures. While they recognize that rehab is important, they're not yet convinced that PTs have the training, or are sufficiently well-versed in the specifics of what is needed by a regenerative patient, to make that referral for physical therapy."

    Her goal in teaching others what she knows, she says, is to facilitate collaborative relationships between regenerative physicians and PTs. It also is to ensure that individuals who undergo regenerative procedures can receive the rehab they need from a local PT. "I have some patients who travel a long way to get here, but that's really not best for them," she says. "What's best is for them to connect with therapists in their area who know what they're doing and are keeping up on the science as it evolves."

    "Exciting" Times

    The evolving science has been a point of interest for Steve Wolf, PT, PhD, FAPTA, FAHA, since at least 2002. During a session at APTA's annual conference that year, he cited regenerative medicine and rehabilitation as being among several emerging fields that one day would have a place within the physical therapy profession. Wolf, a professor in the physical therapy division in the Department of Rehabilitation Medicine at Emory University in Atlanta, later helped organize a group of APTA members and non-physical therapists to start a project named FiRST (Frontiers in Rehabilitative Science Technologies), which identified 4 areas, including regenerative rehab, as critical to the future of rehabilitation.

    FiRST, Wolf explains, is about building the profession's knowledge base—through research and education—in technology-focused fields. (The other 3 areas under the FiRST umbrella are bioengineering, genomics, and telehealth). And when it comes to regenerative rehabilitation, Wolf says, that base is growing "exponentially" every year. "Just to give you an idea" he says, "there were almost as many papers published in the last 18 months under the title 'regenerative rehabilitation' as a subcategory of 'regenerative medicine' as there had been in all the years prior. So the knowledge is increasing, and it's all very promising. But," he adds, "we're still not there yet."

    The profession isn't "there yet," Wolf continues, because, while regenerative therapy is "beginning to enter the classroom, and we're seeing the topic more at various symposia," the evidence for the effectiveness of regenerative rehabilitation "has not yet been convincingly ascertained." He's not saying, he emphasizes, that PTs shouldn't be trusted by physicians to help guide individuals within this patient population back to health. It's just that the therapeutic strategies and principles around these medical procedures won't gain widespread acceptance until they're "completely understood by the PT community."

    Fabrisia Ambrosio, PT, MPT, PhD, agrees. Ambrosio, assistant professor in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh and director of the Cellular Rehabilitation Laboratory there, says, "We have started to see regenerative rehabilitation gain momentum, especially in terms of recognizing that we need more research in the area."

    To that end, last September, the Alliance for Regenerative Rehabilitation Research and Training (AR3T)—a group Ambrosio founded with her colleagues at Pitt's McGowan Institute for Regenerative Medicine and individuals at several other institutions—was awarded a $1.1 million grant by the National Institutes of Health's National Center for Medical Rehabilitation Research.

    AR3T, Ambrosio explains, was created to bring regenerative-medicine scientists together with rehabilitation researchers and clinicians. "Our goals are twofold," she says. "First, to focus on education—on giving rehabilitation clinicians foundational knowledge in regenerative medicine and stem cell biology," as well as the tools they need to collaborate effectively with regenerative-medicine physicians. The second goal is to promote that collaboration in the laboratory, "so clinicians and scientists are working side-by-side to develop and answer the research questions that will continue to move the field forward."

    Ambrosio, who back in 2011 was responsible for the email that Kristin Bowne and other PTs received—and who now is preparing for the fifth iteration of the same event, to be held this October at Emory—calls the current climate around regenerative medicine and physical therapy's role in regenerative rehabilitation "exciting." The basic-science community, she notes, citing as evidence a recent article in the cell and molecular biology-focused magazine The Scientist, "is now recognizing how vital rehab is to this area."

    That piece, published in December, stated that stem cell therapies and tissue engineering were "nearing medical prime time" and that a "growing number of scientists, clinicians, and physical therapists now are taking an interdisciplinary approach to rehabilitation, pairing exercise with technologies that regenerate bone, muscle, cartilage, ligaments, nerves, and other tissues." In the article, Carmen Perez-Terzic, a cardiovascular disease researcher at the Mayo Clinic, described regenerative rehabilitation as "a new future" and predicted "It's going to explode in the next 5 or 10 years."

    When she hears such statements, Ambrosio says, she knows regenerative rehab has turned the corner. "For a cell-biology publication to be making the case that, 'Hey, you should be thinking about these rehabilitative protocols and how they'll play a role in translating your technologies,' I think that shows we're making great progress."

    Working Outside the Boundaries

    Further evidence of this progress can be found at MD Anderson Cancer Center in Houston, where Kimberly Presson, PT, DPT, CLT-LANA, is a senior PT in the Department of Rehabilitation Services. She works primarily with patients who are there to receive treatment for diseases and disorders that include leukemia, lymphoma, and myeloma. Almost all those patients have had stem cell transplants, she notes—including autologous transplants, in which the patient's own stem cells are collected prior to chemotherapy and/or radiation, then transplanted back, and allogeneic transplants, in which patients are given healthy donor stem cells in place of their own.

    The typical stem cell hematology patient remains at the hospital for about a month. (MD Anderson can accommodate up to 96 patients at any time.) "Our first goal," Presson says, "is to see to them as early as we can," before the transplant, if possible. She and her colleagues—including other PTs, physical therapist assistants (PTAs), and occupational therapists—lead patients through several low-intensity group-exercise classes each week. All patients who are able to attend are encouraged to do so. "We know that, given their chemotherapy, we're probably not going to make them a lot stronger, but we do want them to maintain the strength they have," Presson says.

    Patients who are too weak to take the classes are seen 1-on-1, she adds. "Usually for them it's about working on their mobility and core strength, and getting them out of bed, even if it's just to a chair."

    Posttransplant, physical therapy interventions continue—provided the patient is able. "These patients have totally depleted bone marrow with very low hemoglobin and platelets, so we have to pay attention to their blood counts," Presson says. "They also are fatigued. They're so tired from the treatment, we do only as much as they can tolerate, even if it's just a few exercises in the bed."

    Determining the approach to take with each patient requires close collaboration with other health care professionals, Presson adds. "We're in constant communication with either the nurses or the clinical nurse leaders," she says. "If somebody is on my list for the group class but hasn't come in 2 or 3 days, and I haven't seen that individual walking, the nurse probably has some valuable information for me."

    Every Thursday, all those involved in patient care spend an hour together in interdisciplinary rounds discussing each case. "The clinical nurse leaders, PTs, OTs, the dietician, the case manager, the social worker, the chaplain, ethicists, we all sit down together and make sure everyone knows exactly what's going on."

    Presson first worked with stem cell patients during a clinical rotation at MD Anderson when she was still was in school. After graduation she spent 2 years in outpatient orthopedics before returning when a position opened up. "Most of what I've learned about regenerative rehabilitation has been through on-the-job training," she says. "At a lot of the hematology courses a PT might attend, they'll tell you that you can't work with a patient with a hemoglobin under 8 or a platelet count of less than 10. Well, if my patients have a hemoglobin in the mid- to high-7s, that's a good day," Presson says. "So, we're basically working outside the boundaries of what most clinicians would consider normal. But we have to. If we don't, the patient's condition probably will get worse."

    The physicians with whom she works, she says, "really appreciate the benefit of our services" and recognize that undergoing therapy immediately posttransplant may be the key to their patients' success. "Just the other day, I heard a physician telling all of his patients, 'Look, you really need to listen to this lady and do what she asks. She's the one who's going to get you out of here,'" Presson notes.

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    Justin Reyes, PTA, works with patients at the MD Anderson Cancer Center under the supervision of Kimberly Presson, PT, DPT, CLT-LANA.

    Justin Reyes, PTA, who works with many of Presson's patients before and after they've had their stem cell transplants, has heard similar advice from MD Anderson's physicians. He also has seen the determination of those patients. "The majority of them come in here just hoping for a second chance. They're motivated; they want to return to their lives. Sometimes they're tired. Or maybe they're nauseated. But they're usually still willing to do something, even if they can't do a lot."

    Reyes describes working with a recent patient who "we really thought wasn't going to make it." But then, Reyes says, "that individual was able to push and work and go to rehab, then on to outpatient care, and now the patient is back home in El Paso. That kind of thing makes this job rewarding."

    PRP: Simulating Injuries To Stimulate Healing

    While advances such as tissue-engineered bladders and vascular grafts are the headline-grabbers of regenerative medicine, far more common is a simpler procedure involving injections of platelet-rich plasma (PRP). "The number of physicians performing PRP procedures has skyrocketed during the past 5 years," says Stephen Clark, PT, DPT, MBA, OCS, president and founder of Athletic Physical Therapy in Los Angeles. He's even had them himself, he notes—in both Achilles tendons and in a knee.

    The procedure, Clark explains, involves a series of injections of a patient's own blood after it has gone through a multistage centrifugation process that increases platelet concentration to 5-8 times its normal level. Once administered, the PRP simulates an injury at the site of the injection, which in turn triggers the body's healing response.

    "One of the issues with PRP is that there's no single protocol all physicians follow," Clark says. "Different physicians will use different platelet concentrations for the same injury. Some add activators [to stimulate healing], while others don't. One might do 30 fenestrations [at the injection site] while another does 5." Thus, he notes, while "everybody calls it PRP, it's highly variable."

    Still, Clark says, the patients he sees—primarily athletes who are dealing with nagging pain in their elbows, knees, hips, and Achilles tendons—"seem to benefit" from the procedure. "But they do need rehab afterward," he adds, "because it's just as if they've been hurt again." For that reason, he explains, he treats most of his PRP patients as though they've experienced an acute injury.

    "We basically start at square one, and if I can get to them before their injection, that's even better." For those patients, he'll typically try to stimulate blood flow to the injured area using instrument-assisted soft-tissue massage. The idea is to "provoke the injury a little" to kickstart the inflammatory response.

    After the injection is administered, it's usually recommended that the patient rest for a few days before starting physical therapy. "Once they come in, the main thing"—and the biggest difference between a PRP patient and most others—"is that, instead of trying to calm the inflammatory process down, we're trying to help it continue for 7-10 days." Clark varies therapy according to each patient's tolerance, but he also works closely with physicians to ensure that everyone is on the same page. "They're often pretty conservative," he says. "They don't want you to go too fast."

    In his own case, Clark says, his PRP injections have worked as advertised for almost 10 years. And he's seen similar results with his patients—watching them, after they've finished their therapy, return to the sports and activities they love. "Insurance companies still consider PRP to be experimental," he notes, explaining that all of his PRP patients pay cash. But Clark believes it won't be long before the procedure is covered.

    Stem Cells in Orthopedics

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    Angie Garrett, PT, MS, OCS, BCB-PMD, and a patient.

    Angie Garrett, PT, MS, OCS, BCB-PMD, works closely with a physician to provide a new option for patients with osteoarthritis of the shoulder.

    Garrett, a PT at Mission Hospital in Mission Viejo, California, explains, "Studies have shown that when stem cells are injected into an area of damaged tissue, they begin to differentiate into the tissue of the designated area, resulting in the regrowth of new healthy tissue. These procedures typically are minimally invasive," she notes, resulting in lower risks than with a conventional surgery. In the case of the shoulder, she adds, "the theory is that stem cells will differentiate into articular cartilage, returning the joint to a healthier functional state."

    She works with orthopedic surgeon Ralph Venuto, MD, of Newport Beach, California. He performs an arthroscopic debridement on the patient prior to surgery to optimize the stem cell uptake by the joint surface. The patient also undergoes a course of rehabilitative physical therapy. "The purpose of physical therapy," Garrett explains, "is to regain as much mobility in the shoulder as possible, control pain and inflammation, and prevent the development of adhesive capsulitis, effectively preparing the shoulder for the stem cell procedure."

    Venuto uses both PRP and stem cells from adipose tissue, as well as hematopoietic stem cells from the bone marrow. Then comes a waiting period. "Immediate physical therapy will accomplish nothing," Garrett explains, because the stem cells first must transform into new, regenerated cartilage. Physical therapy often begins about 2 weeks after the procedure and will continue for several months afterward.

    "Although it is in its infancy, regenerative medicine is providing an additional option to these patients," Garrett says. "Not surprisingly, these procedures are creating a nascent physical therapy niche, as well."

    Kristin Bowne sees a similar future for stem cell injections and other regenerative techniques, and the PT-led rehabilitation that often follows the procedures.

    "This stuff works," she says. "Biological injections combined with rehabilitation are generating positive results," she says. It saves people time, it saves them from lost work, and it's going to start replacing a lot of surgical procedures." She recently saw a patient who had both PRP and stem cell injections to heal tears in her thoracic spine. As the patient's PT, Bowne's job now is to "restore the altered biomechanics she's developed due to compensatory patterns, so that she doesn't wear the discs down again."

    Regenerative medicine offers "a great opportunity for rehab science, and for PTs to get involved." Bowne says. "It's so exciting—like this big, wide-open door."

    Chris Hayhurst is a freelance writer.

    For More Information

    American Physical Therapy Association

    Regenerative Rehabilitation: www.apta.org/RegenerativeRehab/

    Learning Center: Course LMS-426: Physical Therapy and the Future of Regenerative Medicine (http://learningcenter.apta.org/)

    Alliance for Regenerative Rehabilitation Research and Training (AR3T)

    www.ar3t.pitt.edu/index.html

    International Society for Stem Cell Research

    www.isscr.org/

    Mayo Clinic Center for Regenerative Medicine

    www.mayo.edu/research/centers-programs/center-regenerative-medicine

    McGowan Institute for Regenerative Medicine

    www.mirm.pitt.edu/

    National Institutes of Health's National Center for Medical Rehabilitation Research

    www.nichd.nih.gov/about/org/ncmrr/Pages/overview.aspx


    Comments

    Hello, my name is Sheila and I am interested in getting information on the type of physical therapy that you are doing for a stem cell treatment. I received stem cell/ Platelet injections for my hip four months ago. I started physical therapy about a month after the procedure. I'm their first stem cell patient. Their style is not typical but again if I could get some information of what you are doing it would be very helpful. I'm just a bit discouraged. Trying to do everything I can before making the decision for a hip replacement. I live in northern Ca. at least 4 hours away from you. Is there someone close to Ukiah or Santa Rosa That you could recommend. Thank you for any advise, Sheila Fetzer
    Posted by Sheila Fetzer on 5/25/2016 11:39:22 PM
    It's important to distinguish the putative effects of stem cell therapy from the possibility that stem cells develop into other cell types, eg, cartilage or connective tissue. In many other fields, injections of various kinds of stem cells have produced positive results, but the stem cells themselves were gone in less than a week. That raises the possibility that stem cells may elicit growth factors themselves or from other cells in the region, cause other cells to proliferate and differentiate, and a do a variety of other functions, but without the stem cells themselves differentiating and providing desired functions. This is not to say that stem cells may not do so in certain circumstances, but improved structure and function can not necessarily be attributed to stem cells differentiating and becoming part of the local cellular make up. To show that, one would need to be able to identify progeny of the stem cells, such as by using some sort of molecular tag.
    Posted by Dan Keller on 7/13/2016 2:18:33 PM

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