Regenerative Rehabilitation and Genomics: Frontiers in Clinical Practice

Physical Therapists Play a Role Both After and During the Regenerative Process

The potential to synergize rehabilitation practice and regenerative medicine technologies is elegantly outlined by Thompson et al² in this issue. As they note, the concept of mechanical forces as a means to promote tissue healing is not new. According to Khan and Scott,³ in the late 19th century, the Oxford English Dictionary defined the term mechanotherapy as “the employment of mechanical means for the cure of disease.” Although mechanical stimulation has been a part of the history of physical therapy since our profession's inception, the underlying molecular and cellular mechanisms guiding tissue regenerative responses to physical forces have been all too often underappreciated. Here, Thompson and colleagues offer a contemporary view of mechanotherapy by canvassing principles of mechanobiology and its relevance to physical therapist practice. They offer a concise yet comprehensive primer of our current understanding of the cascade of events by which physical forces may be converted into targeted cellular and tissue responses. Importantly, they highlight the fact that physical therapists play a critical role in facilitating tissue function not only after regeneration has occurred but during the regenerative process. We believe this will be critical to the success of regenerative technologies, as physical therapy will undoubtedly be an indispensible tool for ensuring that the integration of regenerative medicine technologies into the host tissue is relevant in terms of function.

Building on this framework, Han et al⁴ present a case series that illustrates the potential of regenerative rehabilitation to influence physical therapist practice. They use nerve conduction studies and electromyography to evaluate physiological muscle properties following bioscaffold implantation—a tissue engineering approach—in 8 people with a chronic volumetric muscle loss injury. The goal of implantation of this acellular scaffold is to stimulate endogenous stem cell regenerative responses and promote the restoration of tissue function. Some individuals have dramatic increases in functional recovery following scaffold implantation, whereas others have only modest benefit, if any benefit at all. Clearly, the successful integration of this tissue engineering approach into clinical practice is dependent on selection of the most appropriate candidate for surgery and on a better understanding of physiological responses to scaffold implantation and how physical therapists may be able to optimize those responses in a patient-specific manner.

“The Genomic Era Is Upon Us”

The completion of the Human Genome Project in 2003 marked the dawn of the genomic era and the birth of personalized medicine. It provided a new understanding of the importance of genetics in predicting, diagnosing, and treating individual health conditions. Indeed, such personalized medicine has begun to impact virtually all areas of medicine, and physical therapy will be no different. Patient responses to rehabilitation interventions are notoriously variable despite apparent similarities in impairment profiles. One of the greatest challenges for any therapist is deciding which intervention is best suited for an individual patient. We are rapidly approaching an era when understanding genetic variation will help physical therapists better understand the individual differences contributing to impairment manifestation, treatment response, and overall patient wellness. Providing therapists with better tools for stratifying individual patients will undoubtedly enhance the impact of therapy.

Curtis et al⁵ review how genetics and personalized medicine have enhanced the ability to preserve wellness through diet and exercise and optimize treatment for cardiovascular disease and osteoarthritis. Curtis and colleagues show us that “the genomic era is upon us” and explain why physical therapists need to be prepared to include genomics as a factor in guiding patient wellness.

Another paper on genomics borrows from recent advances in functional neurogenomics showing the presence of genetic variations within genes encoding for “plasticity proteins” thought to mediate behavioral recovery. Kim and colleagues⁶ highlight that the presence of a single nucleotide polymorphism within the brain-derived neurotrophic factor (BDNF) gene is associated with altered patterns of brain activity in patients with stroke following robot-assisted motor rehabilitation. Patients who had the polymorphism demonstrated decreased brain activity during movement of the paretic hand in comparison with patients who did not have the polymorphism. Such changes in brain activity may be indicative of differential responses to motor rehabilitation.

The Next Generation

To wrap up this month's installment of the special series, Norland et al⁷ present an unprecedented Perspective—unprecedented because it is written from the point of view of doctorate of physical therapy (DPT) students. Under the mentorship of Dr. Rumit Kakar, DPT students from 4 different universities converged to survey DPT program faculty and students from across the country. The objective of the survey was to gauge the perceived importance of regenerative rehabilitation and genomics on physical therapist practice and how this perceived importance matches up with the incorporation of such concepts into DPT curricula. Compiling more than 1,000 survey responses, these authors bring to light a stark disconnect between “importance” and “incorporation.” Unfortunately, even though education programs generally recognize that innovative technologies are “highly relevant” to physical therapist practice, few programs effectively incorporate the material into their curricula. Based on these findings, the authors provide recommendations for bridging the gap between the basic sciences and education and for inspiring the next generation of physical therapist clinicians. Topp⁸ contributes a thoughtful “Program Director's Response” to the students' Perspective. She gives a historical framework for the need to incorporate innovative technologies into practice, references valuable resources available for those who want to learn more about the emerging fields of regenerative rehabilitation and genomics, and suggests targeted steps for ensuring that DPT students learn about state-of-the art technologies that will one day affect their clinical practice and research.

We hope that this special series on Regenerative Rehabilitation and Genomics will further stimulate discussion about the growing role of innovative technologies for rehabilitation practice and that manuscripts on these topics will continue to be submitted to PTJ to extend this series. We are so grateful to the authors who contributed to this series with their thought-provoking perspectives and cutting-edge research. We also sincerely appreciate the time and expertise provided by the reviewers, whose efforts greatly strengthened the impact of the series; they are listed here. Finally, we extend our heartfelt thanks to former Editor-in-Chief Dr. Rebecca Craik, who offered invaluable support and advice throughout the development of this series.