The world is on the threshold of a new era in medicine—driven, in equal parts, by innovation, natural scientific evolution, and sheer necessity. Conventional medical approaches are unable to adequately address the monumental healthcare challenges faced today and, perhaps even more so, in the coming years, both in the U.S. and globally. The prevalence of serious diseases and conditions are on the rise, taxing our healthcare system and exerting a tremendous economic burden on society. The addition of 30 million new Americans in health insurance programs will further strain the U.S. healthcare system in the coming years. From diabetes to cardiovascular disease, cancer to Alzheimer’s disease, the statistics are staggering and the unmet clinical needs dramatic. It is clear that we must explore new, innovative, and multi-dimensional ways of tackling these problems.
Many current therapeutic and clinical approaches are limited from an efficacy perspective—they are not able to address the underlying cause of disease, alter its course, or reverse damage that has already occurred. Current treatments and procedures are also associated with side effects that result in poor outcomes. Given these troubling inadequacies, it is not surprising that there is a renewed focus on regenerative medicine, and that it is one of the fastest growing life science sectors. The concept of harnessing the power of the human body to heal and regenerate itself does not just signal progress; regenerative medicine could revolutionize healthcare, leading to new treatment paradigms and improved, long-lasting efficacy, and delivering better outcomes and cost-critical efficiencies.
Key challenges damper early hopes
For many people—even those within the medical field—cell therapy is at once fascinating and perplexing, exciting and daunting. The theory behind cell therapy is not new, yet the real-world application of cell-based therapy to treat disease and accelerate healing is still in its relative infancy. In the past, there have been high hopes for cell therapy, but they have been tempered by somewhat disappointing results due to several reasons. For one, it has proven tremendously difficult to transform basic research into viable therapies. There have not been well-developed strategies or infrastructures in place to move concepts from “bench to bedside”. In certain instances, it has been difficult to demonstrate that cell-based therapies have greater efficacy and/or safety than conventional therapies.
Commercial challenges have limited current therapies on the market. The types of cells previously available for research and development were fairly limited, and the technologies needed to ensure scalability were ill-defined. This has led to difficulties in producing cells efficiently and consistently in large quantities and complicated, time-consuming obstacles, such as the involvement of tissue matching and immunological profile of allogeneic stem cells. Similarly, the utilization of autologous cells requires an intricate and involved process of harvesting cells from a patient, manipulating cells, and then reintroducing the cells.
Embryonic stem cells, one of the initial key focal points of cell-based therapy, have long been at the center of a highly publicized and controversial debate. In addition, there have been persistent scientific quandaries, such as how to prevent stem cells from continuing to grow and divide beyond the intent of therapy, which could lead to life-threatening problems for patients. Undoubtedly, some of these issues still linger. However, as a result of significant advances in the past decade—even the past five years—there is notable momentum and excitement in this emerging field of medicine.
Advancements promote progress
The evolution of strategies and paradigms will provide the preclinical and clinical services necessary to carry cell therapies through research and development to successful commercialization. The moral dilemmas surrounding the use of embryonic stem cells have been mitigated through the increased application of adult stem cells, or pluripotent stem cells that can be “reprogrammed” to assume an embryonic stem cell-like state, and act as the repair system of the body.
At the same time, the industry has gained a greater understanding of how to improve the tolerance of the immune system to allogeneic cells and has begun implementation of allogeneic cell types, whose role in various biological processes is well understood. The use of allogeneic cells may enable “off the shelf” administration of therapies, eliminating the difficult processes that plague autologous cell use, and helping overcome some of the present major barriers to commercial adoption. Another critical area receiving increased focus—and essential to the ultimate success of cell therapies—is the exploration of novel delivery mechanisms to safely, efficiently, and effectively introduce cells into the human body. Traditional injection methods often result in poor cell survival and limited cell integration into host tissue. Various new techniques, such as embedding cells in a polymer matrix for delivery, have demonstrated the ability to maintain cell viability and function, helping cells survive and integrate appropriately into the body while mitigating cell loss, as well as erratic and potentially harmful cell behavior.
There has been a virtual explosion in the number of disorders that are being targeted for treatment with cell-based therapy, such as diseases of the nervous system, like Alzheimer’s and amyotrophic lateral sclerosis, cancer, cardiac disorders, diabetes mellitus, diseases of the bones and joints, genetic disorders, and skin and soft tissue wounds.
Pervasis Therapeutics (Cambridge, Mass.) has been focusing on harnessing the power of the body’s own “bioregulatory factory,” the endothelium, to promote a proper healing response. In the vascular system, endothelial cells, which line the interior surface of blood vessels, play a key regulatory role to maintain health, ensure normal blood flow and proper healing. However, the endothelium is disrupted during interventional or surgical procedures. This can trigger a number of unwanted medical events and prohibit normal healing. Recently, it has been found that introducing a healthy, functional tissue engineered endothelium at the time of intervention can reduce common complications and improve outcomes. Pervasis is currently exploring this potential in a number of indications, such as improving the viability of access grafts or fistulae in patients on hemodialysis, improving outcomes following angioplasty and stent implantation in patients with peripheral arterial disease, and reducing the potential for metastasis following cancer treatment.
Changing the tide
Other prominent life sciences companies are now investing heavily in cell therapy. In 2008, Pfizer created a regenerative medicine division and announced that the company was funding a new adult stem-cell treatment that could treat diabetes-induced retinal damage. In 2010, we witnessed the first approval by the U.S. Food and Drug Administration (FDA) of a cell-based immunotherapy (Dendreon’s PROVENGE). Even Google Ventures has indicated that regenerative medicine will be one of its primary areas of interest for investment. In addition, most major universities have now created academic and research programs dedicated to the field of regenerative medicine, which will aid in augmented research and commercialization efforts.
Regenerative medicine and cell therapy are poised to have a tremendous impact on the future of medicine by delivering more efficacious, long-lasting, safe and cost-effective therapies for life-threatening and life-altering conditions than are currently available today. True scientific progress is the result of gradual and painstaking process involving imagination, dedication, and perseverance. By learning from the mistakes of the past, exploiting the advancements of the present, and preparing for the challenges of the future, the long-held promise of cell therapy may soon come to pass.
About the Author
Prior to joining Pervasis in 2008, Frederic Chereau held marketing, business development and general management positions with Genzyme’s cardiovascular business unit where he focused on commercialization of a hypercholesterolemia product and development of a late clinical stage cell and gene therapy programs.