Latest Trends in Regenerative Medicine

Healthcare and medicine are in a constant state of evolution. Innovative technologies such as regenerative medicine are bringing about a paradigm shift in the healthcare industry. While the segment does raise some moral questions, it is witnessing huge capital infusion from pharmaceutical companies. Despite the major challenges associated with regenerative medicine, industry trends indicate that it is poised for growth.

Radical technological advances have accelerated the pace of innovation in medical science. Regenerative medicine is an emerging technology that is set to revolutionize healthcare. As the name suggests, regenerative medicine aims to develop processes and methods to regrow, regenerate or repair diseased or damaged cells, tissues, or organs. It includes the engineering of human or animal cells to restore their original functions. Some of the key regenerative medicine modalities are gene therapy, cell therapy (including stem cell therapy), tissue engineering, and artificial organ development.

Regenerative medicine and therapies are being tested for a broad range of indications such as cancer; neurological indications; cardiovascular disease; inflammatory and immune conditions; endocrine, genetic, and metabolic disorders; and musculoskeletal and ophthalmological conditions. There is considerable scope for regenerative medicine.

The field is in a nascent stage and the term "regenerative medicine" was coined by William Haseltine in 1999 to describe an emerging branch of medicine that focused on tissue engineering and stem cell biology. The field has now gained prominence, with a handful of cell and gene therapy products receiving FDA approvals in the last five years and with several regenerative therapies being assessed in preclinical and clinical settings.

Key trends driving this industry are as follows:

1. Gene therapy expansion – Gene therapy is gaining acceptance and some big pharmaceuticals have received regulatory approvals to launch their products. These therapies are usually very expensive, but the high cost is justified against a lifetime of treatment expenditure. In the US, medical insurance companies are ready to insure such treatments, albeit with some caveats. So far, the US FDA has approved only two commercially available gene therapy products (Novartis' Zolgensma and Spark Therapeutics' LUXTURNA). However, regulatory programs introduced by the FDA – such as the Regenerative Medicine Advanced Therapy designed to fast-track gene therapy product review – have witnessed 30–40 applications with ~30% grant rate in each of the last five years, indicating rapid growth in this space. Favorable regulatory frameworks and advances in delivery technology would spur growth in the domain, which is predicted to expand at a CAGR of ~26% over the next four years, to reach US$ 21.3 billion by 2026.
2. Accurate data requirement in cell therapy – Cell therapy has great potential to eradicate fatal diseases, especially cancer. Currently, FDA has approved Yescarta by Gilead and Kymriah by Novartis, which are chimeric antigen receptor T (CAR-T) cell therapies. Over 800 clinical trials are estimated to be ongoing for various cell therapies to treat cancer. However, recent evidence shows that these therapies have inherent side effects such as neurotoxicity and cytokine release syndrome (systemic immune storm) due to the chimeric antigen receptor, which is designed to bind cancer cells and generate a targeted and amplified immune response against them. At present, there is no long-term reliable data that can reflect the outcome over a period of time. However, the industry and academia are focusing on developing next-generation CAR-T cells that would generate the targeted immune response without triggering a cytokine storm.Another challenge in cell therapy is the manufacturing of the products. The most common approach is to use a patient's cells; however, to make it a usable product, it must be manipulated and expanded. Unfortunately, this does not result in the desired outcome every time. A lack of reproducible methodologies for providing autologous cell therapy is posing a major hurdle to growth in the segment.
3. Lack of acceptance – Traditional surgical interventions are still preferred over tissue repair solutions. However, in sports injuries, novel regenerative therapies are seeing growing acceptance. Research is underway to use stem cell therapies for Parkinson's disease and heart failures as well. Notably, Japan has conditionally approved Terumo's HeartSheet for medical use. This is a tissue-based and cellular product created specifically to treat severe heart failure due to chronic ischemic heart disease. In this treatment, skeletal myoblast sheets are created by culturing skeletal myoblasts enclosed in muscle tissue taken from the patient's thigh. These sheets are then transplanted onto the surface of the patient's heart.

The ethical debate

Progress in this field has been slow, as the process of deriving human embryonic stem cells from human embryos and manipulating the genetic material evokes a strong negative narrative of researchers playing god. The discovery of methods for inducing adult (differentiated) cells to de-differentiate and generate induced pluripotent stem cells was considered a solution. However, it has exacerbated the issue by democratizing the technology for generating stem cells, making the creation of embryos with a customized genetic material a more realistic possibility.

Organogenesis and tissue engineering are more evolved and nuanced applications but raise another ethical question. On the one hand, creating transgenic animals comprising human organs modified to mimic the human system’s biology could bridge the supply-demand gap of organs for transplant procedures. On the other, it could provide an impetus to the burgeoning back-alley market of organ trade. A more far-fetched possibility, as seen in science fiction, is the generation of chimaeras.

The final and biggest ethical challenge is the emergence of a huge market offering unproven "stem cell" treatments. Clinics have suddenly popped out in every obscure part of the world selling treatments they claim are based on stem cells. Most of these treatments have no scientific or clinical evidence and likely provide no benefits. Healthcare professional and researchers in the field have condemned such clinics and warned patients to stay away from unsubstantiated treatments. Unfortunately, such clinics have also negatively impacted the development of genuine therapies by diminishing public and investors' faith in the promising field of regenerative medicine.

Challenges

Some major challenges must be addressed before this segment can see further advancement. The main concern remains tight control over stem cells, induced or isolated from adult tissue to monitor their behavior for safety after transplantation. This can be done by creating microenvironments that provide specific cues and are modeled on various stem cell niches.

Secondly, technology is needed to create large, engineered replacement tissues that allow complete vascularized grafts to be anastomosed with host vessels at the time of transplant, facilitating graft survival.

Lastly, with studies that could better understand the immune system, therapies can create a pro regeneration environment within the patient that could positively affect the outcomes of regenerative medicine.

Outlook

Materials play an essential role in regenerative therapies. With advanced research, sophisticated grafts have been developed to exploit the properties of scaffolding materials. New cell manipulation technologies also modify cell behavior and repair tissue. Other innovative treatments are being researched to improve graft integration with the host vasculature and nervous system, e.g., controlled release of vascular cell seeding and growth factors. The body's healing response can be accelerated in various ways, including immune system modulation.

Regenerative medicine has significant potential to cure fatal and degenerative diseases. The human body is a complex machine; recreating the tissues and organs within this machine is complicated. Substantial research and study are required to make regenerative medicine a mainstream treatment option. Though VCs and pharmaceutical giants have shown interest in the field and are investing in it, the lack of awareness and high costs mean there is a long road to travel for regenerative medicine.