Sisyphus, the Giffen's paradox and the Holy Grail: time for organ transplantation to transition toward a regenerative medicine-focused type of research

Peloso, Andréa; Katari, Ravi; Zambon, João Paulo; Orlando, Giuseppe

doi:10.1586/1744666x.2013.828887

Cited by 9 publications

(5 citation statements)

References 13 publications

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“…Cell-scaffold technology provides the possibility to recapture some of those eliminations and thus gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis. Combined with its potential to contribute to the quest for an immunosuppression-free state, the potential for organ bioengineering to provide a theoretically inexhaustible source of transplantable organs justifies dedicated financial investments and research efforts in this direction [20,21,22,23,24,25]. …”

Section: Resultsmentioning

confidence: 99%

Renal Bioengineering with Scaffolds Generated from Human Kidneys

Katari

Peloso

Zambon

et al. 2014

Nephron Exp Nephrol

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Background: In 2012, about 16,487 people received kidney transplants in the USA whereas 95,022 candidates were on the waiting list at the end of the year. Moreover, more than 2,600 kidneys procured annually for transplantation are discarded for a variety of reasons. We hypothesize that this pool of discarded kidneys could in part meet the growing, urgent need for transplantable kidneys using current methods for organ bioengineering and regeneration and surgical transplantation. The recellularization of extracellular matrix (ECM) scaffolds has the potential to meet the uniquely ambitious engineering challenges posed by complex solid organs such as the kidney. Summary: Attempts to manufacture and implant simpler, hollow structures such as bladders, vessels, urethras, and segments of the upper airways have been successful in the short and mid terms. However, the bioengineering of complex solid organs such as the kidney is a more challenging task that requires a different approach. In previous studies, we showed that decellularized porcine kidneys yield renal ECM scaffolds that preserve their basic architecture and structural components, support cell growth in vivo and in vitro, and maintain a patent vasculature capable of sustaining physiological blood pressure. In a subsequent report, using the same methods, we found that detergent-based decellularization of discarded human renal kidneys preserved their innate ECM framework, biochemical properties, and angiogenic capacity and - importantly - a patent vascular network. Furthermore, the process resulted in the clearance of immunogenic antigens, which has monumental implications for clinical outcomes in the long term in terms of graft rejection. Consequently, these kidneys show promise in bioengineering and transplantation. We refer to this avenue of research and development as ‘cell-scaffold technology'. Key Messages: In 2011, more than 4,700 patients died while on the waiting list for a kidney transplant. In this context, we believe that cell-scaffold technology has the potential to form a bridge between regenerative medicine and transplantation surgery. These methods, in theory, could provide a potentially inexhaustible source of transplantable organs. Unfortunately, current investigations are still in their very early stages and clinical translation is not immediately available in the short term. Thus, identifying the most important obstacles confronting cell-scaffold technology and focusing research efforts in this direction will be important for advancing the state of the art and meeting the clinical needs. We believe that cell-scaffold technology research and development would benefit greatly from a deeper understanding of the physiological mechanisms underlying the natural organogenesis, regeneration, and repair that characterize embryonic humans and simpler organisms. Furthermore, the importance of vascularization - the fundamental caveat of modern surgery - cannot be overstated, especially when discussing the implantation of de novo organs.

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Section: Resultsmentioning

confidence: 99%

Renal Bioengineering with Scaffolds Generated from Human Kidneys

Katari

Peloso

Zambon

et al. 2014

Nephron Exp Nephrol

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“…Despite the road to the ultimate objective appears long, winding and difficult (Figure 2), the different RM technologies are still immature and several questions will have to be answered before translation may occur (Table 1), the days when success will be the usual outcome are ahead of us and closer are the days when TM, a discipline that traditionally has been immunology-based [134,135], will realize that RM should become its major research core. If we agree on this, then TM should allocate more funds to RM-inspired research, transplant societies should twin with RM societies and established RM community of practices and committees, transplant journals and conferences should grant the due consideration and visibility to RM manuscripts.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…Further, this research has allowed us to learn more about the structure and function of the organs, and thus confers many indirect benefits as well [71]. For many, organ bioengineering represents the 'Holy Grail' of transplantation, and represents the best hope to achieve organ transplantation with an immunosuppression-free state [14,100]. While there remain substantial challenges ahead before the field becomes a commonplace clinical treatment modality, continuing advances suggest that it is a matter of when, and not if, this field steps further into the mainstream of modern medicine and yields tangible therapeutic benefit.…”

Section: Discussionmentioning

confidence: 99%

“…In most cases, this was performed by seeding the patient's cells onto a scaffold and then surgically implanting the scaffold without subsequent need for postoperative immunosuppression [14].…”

Section: Historymentioning

confidence: 99%

Whole-Organ Tissue Engineering: No Longer Just a Dream

Wrenn

Weiss

2016

Curr Pathobiol Rep

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Purpose of Review The true potential of the field of transplant surgery remains limited due to shortages of available transplantable allografts and, following transplantation, acute and chronic rejection with need for lifelong immune suppression. An alternative approach is to bioengineer organs to be utilized in vivo, replacing diseased or malfunctioning human organs. This revolutionary step in medicine could have virtually unlimited therapeutic potential. Recent Findings Multiple strategies have been used to replicate functional transplantable organs without deleterious host immune response. Common approaches include the use of decellularized tissue scaffolds and of 3D bioprinting. Continuing challenges include engraftment and maturation of recipient cells, and long-term tissue viability and function. Summary We will review in brief the history of the field and the progress to date with multiple organ systems, highlighting our personal experience in lung regeneration. Finally, we will discuss the challenges that lie ahead to reach the dream of fully functional and transplantable bioengineered organs.

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Sisyphus, the Giffen's paradox and the Holy Grail: time for organ transplantation to transition toward a regenerative medicine-focused type of research

Cited by 9 publications

References 13 publications

Renal Bioengineering with Scaffolds Generated from Human Kidneys

Renal Bioengineering with Scaffolds Generated from Human Kidneys

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

Whole-Organ Tissue Engineering: No Longer Just a Dream

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