The gap between organ need and organ availability continues to widen despite substantial public education efforts on organ donation. According to the Health Resources and Service Administration, until May 2017, around 1,17,829 patients were waiting for organ transplantation in the US alone, and the numbers are increasing. The increasing transplant procedures can be attributed to well-developed healthcare infrastructure and availability of expert surgeons and advanced products.
New technologies consisting of stem cells and tissue engineering have the potential to augment organ function or repair damaged organs. If explored to their full potential, organ bioengineering and regeneration technologies hold the promise to address two most urgent needs in organ transplantation - the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs. Major advances and innovations are being made in the fields of tissue engineering and regenerative medicine, and these have a huge impact on three-dimensional (3D) bioprinting of tissues and organs. In brief, 3D bioprinting holds great promise when it comes to developing artificial tissues and organs, thereby revolutionising the field of regenerative medicine.
The market scenario is encouraging. A $25 billion global regenerative medicine market is expected to grow at a CAGR of 23.6 per cent between 2016 and 2021. Government and private funds are also driving the market in areas such as chronic diseases and genetic disorders prevalence. An increase in global healthcare expenditure and rapid growth in the ageing population have broadened the scope further and help target orthopaedic and musculoskeletal disorders, dermatology, cardiology, diabetes and central nervous system disorders. Then again, oncology is expected to become the fastest-growing market owing to the increasing prevalence of cancer globally and a rich product pipeline. Its undeniable significance was underlined when James P. Allison jointly won the 2018 Nobel Prize for Physiology or Medicine for his discovery of CAR T-Cell immunotherapy for treating haematologic malignancies.
Cell therapy and current challenges
Most regenerative medicine strategies evolve around cell sources. Therefore, 3D bioprinted constructs, stem cells, progenitors and differentiated cells, derived from both adult and embryonic tissues, are widely explored in this space. As of now, adult tissue-derived cells are the dominant cell type used clinically due to their ready availability and perceived safety (hence, these are easily approved by the US Food and Drug Administration or FDA). Basic studies aiming to understand the processes that control stem cell renewal are also used for tissue repair and regeneration, with prototypical examples being studied with haematopoietic stem cells (HSCs), which generate other blood cells.
Elucidation of the mechanistic aspects of embryonic development is crucial to understanding the repair of living cells and extracellular material in situ. However, the field is far from yielding therapeutically applicable outcomes from the knowledge gained. Adult tissue degeneration and replacement in an evolutionary context, using efficiently regenerating vertebrate species to analyse the mechanism of repair, often seems remote from a mammalian perspective and is relatively slow to yield mechanistic information. Current approaches that rely heavily on stem cell transplantation and regenerative medicine have an impact on clinical medicine that requires further scientific rigour.
As tissue engineering and regenerative medicine have emerged as an industry, numerous therapies have got FDA clearances and are commercially available. The delivery of therapeutic cells, which directly contribute to the structure and function of new tissues, is a principle paradigm of regenerative medicine. The cells used are either autologous or allogeneic, having the characteristic features of becoming a new cell type such as bone, cartilage and other organs, with a self-renewal capability. For example, Carticel, the first FDA-approved biologic product in the orthopaedic field, uses the product in treating debilitating orthopaedic diseases such as cartilage damage. Here, autologous chondrocytes are harvested from articular cartilage, expanded ex vivo and implanted where the injury is, resulting in early recovery.
Transdisciplinary technological approaches have led to successful 3D printing of biological material - cells, biomolecules and growth factors - in an additive manufacturing set-up. Also, growing regulatory approvals for 3D bioprinting have led to high demand for innovative products which are utilised for regenerating tissues and organs. For instance, Organovo Holdings, a 3D biology company, first announced its 3D liver tissue delivery in January 2014.
Although several possible scenarios have been proposed, stem cell therapy in the future is likely to involve strategies to ensure that stem cells function effectively. This could be done by including inductive microenvironmental niche factors within the target tissue which will optimise the survival and function of the transplanted cells. Alternatively, the use of temporary niches surrounding individual transplanted cells may be required to provide appropriate survival signals. In this regard, there is increasing recognition of a central, perhaps orchestrating, role for immune cells in providing trophic signals to transplanted cells, thus preparing the ground for physiological tissue repair.
Human Organoids are grown in pigs
Genome editing has added a new dimension to producing organs, especially with the advent of induced pluripotent stem cell (iPSC) technology, which is widely exercised in research studies. Xenotransplantation using the pig/mice animal model has been chosen to grow human organoids. Dr. Hiromitsu Nakauchi, a Stem Cell Researcher from Stanford, initially demonstrated the idea of growing the organ of one species in the body of another species (the first two groups chosen were mice and rats, in 2010). Pancreatic islets are now grown in genetically engineered pigs, wherein a healthy pool of insulin-producing islet cells are generated for treating diabetes. Another research group grew human cells in a pig in 2017, offering further proof of principle. Again, human kidneys have been grown in pigs to bridge the gap between demand and supply.
This kind of disruptive technology also holds great promise for organ bioengineering, ushering in a new era of regenerative medicine with a transdisciplinary dimension to medical research and applications. Regenerative medicine is bound to transform organ transplantation by developing a new source of organs or potentially rehabilitating those, which are not transplantable. The years ahead will be extraordinarily exciting and may rival the pioneering years of transplantation.
The writer is founder and chairman, Gleneagles Global Hospitals Group