Rethinking Regenerative Medicine From a Transplant Perspective (and Vice Versa)

Abstract

No field in health sciences has more interest than organ transplantation in fostering progress in regenerative medicine (RM) because the future of no other field more than the future of organ transplantation will be forged by progress occurring in RM. In fact, the most urgent needs of modern transplant medicine - namely, more organs to satisfy the skyrocketing demand and immunosuppression-free transplantation -, cannot be met in full with current technologies and are at risk of remaining elusive goals. Instead, in the past few decades, groundbreaking progress in RM is suggesting a different approach to the problem. New, RM-inspired technologies among which decellularization, 3D printing and interspecies blastocyst complementation, promise organoids manufactured from patients' own cells and bear potential to render the use of currently used allografts obsolete. Transplantation, a field that has traditionally been immunology-based, is therefore destined to become a RM-based discipline.However, the contours of RM remain unclear, mainly due to the lack of a universally accepted definition, the lack of clarity of its potential modalities of application and the unjustified and misleading hype that often follows the reports of clinical application of RM technologies. All this generates excessive and unmet expectations and an erroneous perception of what RM really is and can offer.In this manuscript, we will (i) discuss these aspects of RM and transplant medicine, (ii) propose a definition of RM, and (iii) illustrate the state of the art of the most promising RM-based technologies of transplant interest.

Regenerative medicine, organ bioengineering and transplantation

“…The history of organ transplantation can be split into three phases, or eras ( Fig . 1 ) 7 . The first phase spans from the early days of surgical science (surgery era).…”

“…Possibly the most anticipated and exponential applications of 3D printing are those in tissue engineering, which may collectively be referred to as bioprinting. Biomaterials used for bioprinting constructs compatible with human physiology include both naturally derived polymers (such as alginate, gelatin, collagen, fibrin and hyaluronic acid) and synthetic polymers (for example, polyethylene glycol) 7 . A combination of synthetic and naturally derived polymers produces a functionally superior material that retains both the structural integrity and innate physiological interactions.…”

Emerging technologies in organ preservation, tissue engineering and regenerative medicine: a blessing or curse for transplantation?

“…Ongoing hurdles include the precise positioning of seeded cell types inside the organ or tissue scaffold, providing adequate oxygen and nutrient supply, enabling metabolic waste product removal and minimization of thromboembolic events during recellularization . As well, there is currently a degree of difficulty in achieving adequate lymphatic drainage and vascularization of recellularized organs, something that needs to be addressed to optimize functional outcomes . Nevertheless, other types of scaffolds and ECM generated via decellularization methods are already commercially available.…”

“…This implies that currently, while for some organs interspecies organogenesis is possible, it remains limited by species and organ type. Current research thus focuses on possible modifications of donor iPSCs, better engraftment strategies and enhanced the purity of cellular composition of generated organs .…”

“…Transplant medicine benefits from various aspects of RM, as they offer potential strategies to increase organ utilization, expand the donor pool, generate new organ sources, reduce disparities in and enable fast access to transplantation (‘off‐the‐shelf’), facilitate better matching and lower immunogenicity as well as allow more flexibility and better planning of transplantations . The ultimate goal is the generation of immunosuppression‐free, universally accessible organs‐on‐demand that lack damage from organ preservation and storage .…”