Kidney transplantation, bioengineering and regeneration: an originally immunology-based discipline destined to transition towards ad hoc organ manufacturing and repair

ABSTRACT

Kidney transplantation (KT), as a modality of renal replacement therapy (RRT), has been shown to be both economically and functionally superior to dialysis for the treatment of end-stage renal disease (ESRD). Progress in KT is limited by two major barriers: a) a chronic and burgeoning shortage of transplantable organs and b) the need for chronic immunosuppression following transplantation. Although ground-breaking advances in transplant immunology have improved patient survival and graft durability, a new pathway of innovation is needed in order to overcome current obstacles. Regenerative medicine (RM) holds the potential to shift the paradigm in RRT, through organ bioengineering. Manufactured organs represent a potentially inexhaustible source of transplantable grafts that would bypass the need for immunosuppressive drugs by using autologous cells to repopulate extracellular matrix (ECM) scaffolds. This overview discusses the current status of renal transplantation while reviewing the most promising innovations in RM therapy as applied to RRT.

KEYWORDS:

• Kidney transplantation
• bioengineering
• regenerative medicine
• extracellular matrix
• decellularization

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Key issues

• Advances in immunology and surgical techniques have paved the way for the evolution of modern KT as the most effective modality of RRT.

• The current organ pool largely consists of living donors, deceased donors and suboptimal grafts that meet the definition of “expanded criteria” set forth to expand the supply.

• The existing supply of transplantable organs falls woefully short of the much larger demand for them, resulting in a burgeoning kidney waiting list that has surpassed >101,000 candidates.

• The dilemma of chronic kidney disease is exacerbated by graft rejection and failure resulting in five-year graft survival rates of 68–80%.

• The major problems facing KT, namely organ shortage and the lifelong commitment to immunosuppressive medications, are no longer amenable to immunology-based innovation.

• Recent developments in RM and developmental biology offer definitive solutions to contemporary problems of chronic kidney disease and KT. The most promising strategy is ad hoc manufacture of transplantable organs via extracellular matrix (ECM)-based scaffold recellularization.

• ECM is widely recognized to be a crucial mediator of cellular differentiation, migration, adhesion, morphology and function in vivo and in vitro.

• The seeding of ECM scaffolds with autologous stem cells has the potential to generate viable kidney organoids that may alleviate the organ shortage while bypassing antigenic rejection and the need for immunosuppressive drugs.

• The supply of grafts manufactured ad hoc via advanced methods in bioengineering is theoretically inexhaustible, further underscoring its allure as a possible alternative and even paradigm shift in the treatment of chronic kidney disease.