scholarly journals Whole Organ Engineering: Approaches, Challenges, and Future Directions

2020 ◽  
Vol 10 (12) ◽  
pp. 4277
Author(s):  
Sogu Sohn ◽  
Maxwell Van Buskirk ◽  
Michael J. Buckenmeyer ◽  
Ricardo Londono ◽  
Denver Faulk

End-stage organ failure remains a leading cause of morbidity and mortality across the globe. The only curative treatment option currently available for patients diagnosed with end-stage organ failure is organ transplantation. However, due to a critical shortage of organs, only a fraction of these patients are able to receive a viable organ transplantation. Those patients fortunate enough to receive a transplant must then be subjected to a lifelong regimen of immunosuppressant drugs. The concept of whole organ engineering offers a promising alternative to organ transplantation that overcomes these limitations. Organ engineering is a discipline that merges developmental biology, anatomy, physiology, and cellular interactions with enabling technologies such as advanced biomaterials and biofabrication to create bioartificial organs that recapitulate native organs in vivo. There have been numerous developments in bioengineering of whole organs over the past two decades. Key technological advancements include (1) methods of whole organ decellularization and recellularization, (2) three-dimensional bioprinting, (3) advanced stem cell technologies, and (4) the ability to genetically modify tissues and cells. These advancements give hope that organ engineering will become a commercial reality in the next decade. In this review article, we describe the foundational principles of whole organ engineering, discuss key technological advances, and provide an overview of current limitations and future directions.

2016 ◽  
Vol 38 (4) ◽  
pp. 20-23
Author(s):  
Michelle E. Scarritt ◽  
Stephen F. Badylak

The only curative treatment option for patients with end-stage organ failure is transplantation. Organ engineering offers an alternative to traditional transplantation that may address the critical shortage of donor organs and eliminate the need for recipient immunosuppression. Organ engineering may be accomplished through the use of scaffold – support structures that contain the architecture of an organ. As organs are exceedingly complex, creating an organ scaffold is a difficult task; however, organ scaffolds can be derived through a process known as decellularization, which is the mechanical, chemical and/or enzymatic removal of cells from a tissue or organ. Through decellularization of xenogenic (animal) organs, biocompatible extracellular matrix (ECM) scaffolds can be produced that retain the complex macroscopic and microscopic structure and composition of the native organ ECM. These 3D ECM scaffolds are ideal for engineering human organs.


2018 ◽  
Vol 159 (46) ◽  
pp. 1948-1956
Author(s):  
Antal Dezsőfi ◽  
György Reusz ◽  
Lajos Kovács ◽  
Dolóresz Szabó ◽  
Kata Kelen ◽  
...  

Abstract: Paediatric organ transplantation today is considered and accepted and widely available therapy in children with end-stage organ failure. It is important to know that in childhood, diseases leading to end-stage organ failure differ from those in adults. Beside this, in children there are different surgical and paediatric challenges before and after transplantation (size differences of the patient and donor organ, special and paediatric infections, different pharmacokinetics and pharmacodynamics of immunosuppressive drugs, noncompliance). However, paediatric organ transplantation in the last decades became a success story of the Hungarian health care owing to several working groups in Hungary and outside the country. Orv Hetil. 2018; 159(46): 1948–1956.


Nutrients ◽  
2013 ◽  
Vol 5 (7) ◽  
pp. 2352-2371 ◽  
Author(s):  
Ursula Thiem ◽  
Bartosz Olbramski ◽  
Kyra Borchhardt

2017 ◽  
Vol 40 (4) ◽  
pp. 150-158 ◽  
Author(s):  
Michele Fedecostante ◽  
Oana G. Onciu ◽  
Koen G.C. Westphal ◽  
Rosalinde Masereeuw

Patients with end-stage renal disease often undergo dialysis as a partial substitute for kidney function while waiting for their only treatment option: a kidney transplant. Several research directions emerged for alternatives in support of the ever-growing numbers of patients. Recent years brought big steps forward in the field, with researchers questioning and improving the current dialysis devices as well as moving towards the design of a bioengineered kidney. Whole-organ engineering is also being explored as a possibility, making use of animal or human kidney scaffolds for engineering a transplantable organ. While this is not a new strategy, having been applied so far for thin tissues, it is a novel approach for complex organs such as the kidneys. Kidneys can be decellularized and the remaining scaffold consisting of an extracellular matrix can be repopulated with (autologous) cells, aiming at growing ex vivo a fully transplantable organ. In a broader view, such organs might also be used for a better understanding of fundamental biological concepts and disease mechanisms, drug screening and toxicological investigations, opening new pathways in the treatment of kidney disease. Decellularization of whole organs has been widely explored and described; therefore, this manuscript only briefly reviews some important considerations with an emphasis on scaffold decontamination, but focuses further on recellularization strategies. Critical aspects, including cell types and sources that can be used for recellularization, seeding strategies and possible applications beyond renal replacement are discussed.


TECHNOLOGY ◽  
2018 ◽  
Vol 06 (03n04) ◽  
pp. 118-134
Author(s):  
Saik-Kia Goh ◽  
Suzanne Bertera ◽  
Vimal Vaidya ◽  
Sam Dumpe ◽  
Sierra Barner ◽  
...  

Whole organ engineering has emerged as a promising alternative avenue to fill the gap of donor organ shortage in organ transplantation. Recent breakthroughs in the decellularization of solid organs and repopulation with desired cell populations have generated neo-organ constructs with promising functional outcomes. The realization of this goal requires engineering advancement in the perfusion-based bioreactors to (i) efficiently deliver decellularization agents, followed by (ii) its reconstruction with relevant cell types and (iii) maintenance of viability and function of the repopulated organ. In this study, we report the development and assembly of a perfusion bioreactor with the potential to enable regenerative reconstruction of pancreas. The assembled bioreactor is versatile to efficiently decellularize multiple organs, as demonstrated by complete decellularization of pancreas, liver and heart in the same set-up. Further, the same system is amenable to support organ repopulation with diverse cell types. Using our in-house bioreactor system, we demonstrate pancreas repopulation with both immortalized MIN-6 beta cells and differentiating human pluripotent stem cells. Importantly, we show the significant advantage of perfusion culture over static culture in enhancing cell engraftment, viability and phenotypic maintenance of the repopulated pancreas. In addition, this study is a significant step forward for whole organ engineering as it will facilitate cost-effective and easy assembly of perfusion bioreactors to enable rapid advancement in regenerative organ reconstruction.


2020 ◽  
Vol 26 (28) ◽  
pp. 3497-3506
Author(s):  
Raymund R. Razonable

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
G Valdi ◽  
G Varadi ◽  
A Panzera ◽  
M Parpinel ◽  
R Peressutti

Abstract Problem When WHO declared COVID-19 “international”, it was important not to damage some critical patients who need emergency procedures like organ transplantation, due to end stage organ disease. In 2003 SARS outbreak demonstrated the vulnerability of organ transplantation services o network. Descritption If transplantation is required as a life-saving procedure, it can be conducted with appropriate risk infection assessment. It is crucial during these emergencies to assess donor pool, as it is expected to decrease. A crucial point is to organize and evaluate the surge capacity, in terms of understaffing and lack of supplies, especially in ICU. The research methods were literature review using Pub Med, CDC, ECDC, WHO, TTS, searching as key words “SARS-CoV-2”, “COVID-19”, “transplantation”, “preparedness”. The analysis has been conducted between Feb 26th 2020 and March 5th 2020. Results As happened during SARS breakout in 2003, it is essential to establish a task force for crisis, currently updated and skilled for this particular management. Preparedness should regard especially the adoption of donor safety assessment procedures, ICU capability, the availability of covid-19 test for all the donors, and the adoption of specific post-transplant care. It is essential in this case establish preparedness in several points: education and training of the staff, practice drills, inspection of supplies, evaluation of surge capacity, relocation of patients. Lessons SARS-CoV-2 imposed in public health to establish new protocols and guidelines, which should be regularly updated to be useful in other epidemics outbreaks or other emergency situation. These protocols should focus on donor pool and ICU capability in order to carry on transplantation activities. Key messages This outbreak has tested the resilience of the whole system by day-by-day updating for transplantation teams and preparedness of the staff involved in transplantation management. During outbreak, seems to be useful a task force for crisis in order to support organ transplantation services.


2008 ◽  
Vol 36 (4) ◽  
pp. 760-765 ◽  
Author(s):  
Christopher James Doig ◽  
David A. Zygun

“I think there’s a big strong belief in [...] the community … and maybe it’s in the world at large that somehow the doctors are more concerned about harvesting the organs than what’s best for the patient.”1 In the past 45 years, organ and tissue recovery and transplantation have moved from the occasional and experimental to a standard of care for end-stage organ failure; receiving an organ transplant is for many the only opportunity for increased quantity and/or quality of life. The increasing prevalence of diseases such as viral hepatitis, diabetes, and hypertension has significantly increased the incidence of end-organ failure. Additionally, surgical advances have permitted less stringent qualification criteria, so that people of advanced age or patients who may be in a physiologically fragile state are now eligible to be organ recipients. These changes have created a significant demand for organs.


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