Regenerative Medicine

Why regenerative medicine is vital to your future healthcare career

By Igor Irvin Bussel and Joshua Bakhsheshian
Chicago Medical School
Rosalind Franklin University of Medicine and Science

What is Regenerative Medicine?

Regenerative medicine is the science and practice of creating technologies to repair, rebuild, or replace cells, tissues, and organs to restore or establish normal structure and function in disease states. Therapies include methods and techniques such as stem cell transplantation, tissue engineering, and induction of regeneration by biologically active molecules such as growth factors. The regenerative medicine field has the ability to have significant impact on human health and well-being. Additionally, this approach holds potential to solve the challenges of injury from the battlefield, organ donation shortage, and rejection of organ transplants. The promises of regenerative medicine as a multidisciplinary field are rooted in the foundation based on its origins and development.

Regenerative medicine became a popular synonym for tissue engineering because it embodied the benefit of a therapeutic approach for the patient rather than the technology of the inventor. The term “regenerative medicine” was first introduced in 1992 by Dr. Leland Kaiser in a paper on future technologies that will impact hospitals. In the late nineties, the term was popularized by Dr. William Haseltine during his role as the founder of Liebert Publisher’s first e-journal entitled Regenerative Medicine. Fueled by the latest advances in research, increasing public interest, and entrepreneurial opportunity, regenerative medicine is positioned to revolutionize the healthcare industry.

Regenerative medicine is already transforming healthcare by capitalizing on an increasing aging population that is demanding sophisticated treatments in light of a diminishing pharmaceutical industry pipeline of drug development. As of 2008, the United States spent $2.25 trillion, roughly 16% of the gross domestic product, on healthcare. Accordingly, it is not surprising that the current market for regenerative medicine is $3.6 billion dollars. There are roughly 700 regenerative medicine companies distributed worldwide, many having approved clinical products or products in clinical trial. By the year 2020, people age 65 and older (Baby Boomers) will outnumber children under age 5 around the globe. Additionally, by the year 2020, the Department of Health and Human Services predicts the market for regenerative medicine will reach $300 billion. Consequently, the forces driving this growth will lead to innovation but it will not be without scientific, societal, and economical challenges.

The Approach of Regenerative Medicine

Ideally, the field of regenerative medicine offers a more viable solution to disease than succumbing to the cocktail of pharmaceutical fixes that is currently available. As the Baby Boomer generation moves into old age over the next decade, the care for their age-related degeneration will become inescapable, influencing every medical discipline and specialty. Dr. Aubrey de Grey emphasized the shortcomings of the Gerontology and Geriatric approaches to address the disabilities and diseases of age-related degeneration. Bussel et al. explained that we cannot approach the problem of an aging population with current methods of prevention and conventional curative models. For much of the baby boomer population, prevention will be too late to stall the degenerative spiral and the curative approach is not effective against complex conditions of age-related degeneration. However, regenerative medicine takes an innovative approach to this problem. For example, an individual with end-stage bronchial disease received a tracheal graft from their own mesenchymal stem cells; a treatment option that was once only dreamt of by doctors is now a reality.

Many curative methods risk suboptimal functional outcomes, reoccurrence of original or secondary inflicted complications. Current therapies in regenerative medicine approach this issue by repairing the cells lost to the aging process and ultimately restoring the function of tissues and organs. It is the only approach that can restore the original function of organs for current patients still waiting for transplantations because of the shortage of donors. Preventive and curative approaches are still necessary, but it is important to understand that that regeneration and rejuvenation therapies can close the gaps left behind by these approaches. Once the etio-pathological mechanisms of regenerating tissues to its original function are mastered, preventive methods can be more effective when applied before irreversible damage has occurred. Ultimately, the healthcare industry can change from reducing symptoms and suffering towards restoring population health by actually reversing the pathology.

Specializing in Regenerative Medicine

Age-related degenerative diseases are multi-factorial conditions involving numerous environmental and metabolic factors. It is clear that no single approach exists that will solve all ailments; rather, each pathologic condition and each tissue will require a unique approach to obtain optimal results.  Therefore, one can conclude that these approaches cannot be contained to one specialty; rather, they must be incorporated into the majority of specialties. This allows a multidisciplinary approach towards the field as its scope of research is extremely complex.

Multipotent mesenchymal stem cells have the capacity to undergo adipogenesis, osteogenesis, chondrogenesis, skeletal myogenesis, cardiac myogenesis, neurogenesis and with the potential to become parts of many other systems. All these potentials are encompassed in the scope of regenerative medicine. The field generally encompasses three areas of focus: clinical medicine, cell biology and engineering. The clinical aspect examines the pathology, physiology, radiology, anatomy, and epidemiology aspects of tissue engineering. Basic science studies are there to better understand the blueprint of the organ system such as scaffolds for cell attachment, growth factors and other biological factors.  Mechanical engineering is necessary to design bioreactors, devices that allow for sterile conditions and dynamic cell culture condition. This field promotes the coalescence of relatively new and related fields to achieve a new potential, apparent in its current research studies.

Research in Regenerative Medicine

In the field of regenerative medicine we are looking forward to the development of effective therapies for degenerative diseases, traumatic injuries and disorders, all with current therapeutic limitations. The derivation of blood cells from stem cells, creation of insulin-secreting beta cells responsive to glucose for diabetes, remodeling of the heart after a myocardial infarction, regeneration of nerves after spinal cord injury, and attenuating the pathology of Alzheimer’s disease are all within reach of regenerative medicine. The following studies represent only a glimpse of the current research projects in the field:

Repairing spinal paralysis: Regeneration in acute spinal cord injuries.

-       Permanent paralysis from spinal cord injuries may soon be an affliction of the past. Hans Keirstead et al. demonstrated that human embryonic stem cells (hESC) can be used to treat spinal cord injuries and improve recovery out-comes. The team used rats for cervical injury models and found that hESC transplants decreased lesions, increased sparing of white and gray matter at the injury site and promoted the recovery of forelimb function. The treatment was recently approved by the FDA for clinical trials in humans with acute spinal cord injuries.

Repairing bone defects: Regeneration of bone cells from fat cells.

-       There are estimated to be over 10 million Americans with osteoporosis and 34 million with low bone mass. Rik Derynck et al. demonstrated that cellular therapies can induce osteoblast differentiation from pre-adipocytes. With a careful choice of cell signaling molecules, researchers were able to suppress the development of adipocytes and increase production of osteoblasts.

Repairing organs: Laboratory-grown bladder trans-plants.

-       Anthony Atala et al. transplanted a laboratory-grown bladder into a child with a congenital bladder malformation. The bladder was cultured from the patient‘s own cells, thereby minimizing risks for tissue rejection. The cells were grown over a period of six weeks on a biodegradable scaffold in a medium containing specific growth factors. Atala has since moved on to research the same techniques for the repairs of other organs such as the pancreas and heart, but how successful such efforts will be remains to be seen.

Creating islet cells for type 1 diabetic patients.

-       Today, 20.8 million diabetics are in need of islet cells with only 6,000 available donors. Dr. Jose Oberholzer, the director of cell and pancreas transplantation at the University of Illinois Medical Center at Chicago and other doctors and scientists from around the world are working on the Chicago Diabetes Project to create a functional cure for type 1 diabetes. Dr. Oberholzer et al. are regenerating islet cells harvested from the pancreas, taking care to ensure they don’t lose function or become cancerous in the process. Oberholzer and his collaborators have already begun human clinical trials in Italy with success and is currently working on improving transplant survival using therapeutic agents combined with anti-inflammatory treatments.

Role of transplanted human neural stem cells in brain repair after stroke.

-       Stroke is the leading cause of adult disability and is the second most common cause of mortality worldwide. Tonya Bliss et al. reported the advent of transplanted human brain, bone marrow and blood-derived progenitors to enhance recovery after stroke through neuroimmunomodulatory techniques. Currently the group is optimizing the parameters for clinical trials, working on the timing of the transplantation, testing the route site of delivery, and utilizing PET scans.

Adult stem cell therapy of the infarcted and chronically failing left ventricle.

-       In Germany, Dr. Bodo E. Strauer and his team are developing methods to increase the potency of the stem cells and the effectiveness of this treatment. By a method called “ischemic pre-conditioning” in which they deprive the heart of oxygen or increase the heart’s demand for oxygen, they are able to increase the potency of the stem cells. Studies have shown that stem cell therapy can greatly reduce the rate of mortality among these patients and improve ventricular function for up to five years.

Other regenerative medicine therapies in clinical trials include but are not limited to: regenerative endodontic techniques, periodontal tissue regeneration, repair of knee cartilage, bone marrow stem cells for treating osteoarthritis, lumbar disc degeneration repair, dendritic cell vaccination for myeloid leukemia, and umbilical cord mesenchymal stem cells for liver cirrhosis.

Snake Oil and Pseudoscience of Regenerative Medicine

The potential for regenerative medicine to radically change current clinical therapies will take time to reach the patient bedside. Though the patient community is excited for the impending therapy options, this hype does not reflect current therapeutic applications.

At the present moment, regenerative medicine offers nothing for today’s sick population. It is imperative to state that currently there is no validated regenerative medicine treatment available with a proven efficacy and safety record. However, the astounding research developments and growing popularity of regenerative medicine has led to a number of stem cell clinics around the world offering deceitful regenerative medicine therapies to patients. These international clinics are located outside the United States and promote fraudulent stem cell tourism.

These dubious clinics exploit the promise of stem cells by offering unproven treatments to desperate patients. They provide “cutting-edge” stem cell treatments for a long list of fatal or incurable diseases with no guarantee of help or absence of harm. These procedures are extensively marketed and advertised via the internet as routine rather than experimental treatments and offer patient testimonial to support their treatment rather than published research. Unlike the United States, other countries lack the rigorous oversight and regulation required for developing and offering medical treatments.

The International Society for Stem Cell Research (ISSCR) is a professional organization focused on fostering the exchange of information on stem cell research, educating the public, and directly addressing misleading claims of dubious treatments and products. Recently, ISSCR published a handbook for patients considering stem cell tourism to ensure that the patients make the best decision possible for treatment.

Regenerative research and medicine is constantly developing and the science is very promising. There will be great advances in treating diseases and conditions however at the present moment, any such claim is nothing but 21^st century snake oil.

Potential Careers in Regenerative Medicine

Significant momentum, driven by federal and private funding, has led to the development of over 65 academic medical centers and institutes focused on regenerative medicine. The premier U.S. institutions include: Stanford University, University of California San Francisco, University of Wisconsin, Wake Forest University, and University of Pittsburgh. Every institution involved in regenerative research and medicine combines specialties in an inter-disciplinary approach of generating basic, translational, and clinical science. It is imperative to note that the regenerative medicine industry is significantly productive. Based on assessments by the Proteus Regenerative Medicine investment and advisory firm, there are currently 175,000+ peer-reviewed publications, 10,000+ issued/pending patents, and 900+ FDA-approved clinical trials for regenerative medicine. Potential careers are available for scientists, surgeons, and physicians wishing to work on integrative and innovative ideas with a multidisciplinary team. A major demand in the field is specialized functional expertise rather than a broad understanding general practitioner. Furthermore, as the regenerative medicine field develops and evolves to greater levels of complexity, specialized allied health professionals will become crucial to effectively implement and administer therapies.

Raising Student Awareness

On March 9, 2009, U.S. President Obama signed the Stem Cell Research Executive Order to overturn President Bush’s limitations on using embryonic stem cells for research. Groundbreaking efforts to support regenerative medicine technology such as International Regenerative Medicine Legislative Day, Regenerative Medicine Promotion Act of 2010 and organizations like the Alliance for Regenerative Medicine (ARM), are in place to encourage the development of the industry.

There will still be significant regulatory hurdles that need to be addressed and a better understanding of the different stem cell sources and the implications of their host interactions is required however the potential of innovative treatment is within reach. It is important that medical school students take a proactive approach to move forward with the research to facilitate the development of regenerative care through the medical education environment.

Fostering interests in the developing field of regenerative medicine during medical school is important as the field adapts to the current changes in the healthcare system.  While research programs have developed specific tracks and curriculums for regenerative medicine, there are currently no medical residency or fellowship training programs focused on this path. Thus, it is imperative that future healthcare practitioners with an interest in regenerative medicine independently develop their knowledge and skill-set.

The most applicable abilities can be gained through research experience and background understanding can be achieved via online presentations, research discussion forums, and public presentations at regenerative medicine institutions. Furthermore, networking through peers and mentors remains a viable option for discovering opportunities to explore your interest in regenerative medicine. The Academic Initiative of the SENS Foundation is a student development and research program for undergraduate, graduate, and medical students seriously considering pursuing a career in regenerative medicine to specifically advance rejuvenation biotechnologies to comprehensively address the disabilities and diseases of aging.

About the authors

Igor Irvin Bussel received a B.S. in Biological Sciences from UCI in 2006, M.S.in Biomedical Sciences from RFUMS in 2009, and M.S. in Healthcare Administration and Management from RFUMS in 2010. Currently, he is a 2^nd year medical student and was the Founder of the Regenerative Medicine Interest Group at RFUMS.

Joshua Bakhsheshian received his B.S. in Neuroscience and Physiology from UCSD in 2007 and M.S. in Biomedical Sciences from RFUMS in 2010. Currently, he is a 1^st year medical student concurrently working on a M.S. in Healthcare Administration and Management. He holds office as the President of the Regenerative Medicine Interest Group at RFUMS.

Addendum:

The Bussel et al. article can be found in full at this link.