Cell and organ bioengineering technology as applied to gastrointestinal diseases

Orlando, Giuseppe; Bendala, Juan Domínguez; Shupe, Thomas; Bergman, Christopher R.; Bitar, Khalil N.; Booth, Christopher; Carbone, Marco; Koch, Kenneth L.; Lerut, Jan; Neuberger, James; Petersen, Bryon E.; Ricordi, Camillo; Atala, Anthony; Stratta, Robert J.; Söker, Shay

doi:10.1136/gutjnl-2011-301111

Cited by 41 publications

(32 citation statements)

References 137 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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“…The pancreas serves key endocrine and exocrine functions within the human body; however, the endocrine component (which represents \2 % of the total cell mass of the organ) is the most vital for life and not easily managed medically [37]. The transplantation of islet cells for the management of type 1 diabetes mellitus is already a clinical reality [38,39].…”

Section: Pancreasmentioning

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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“…If isolated and expanded, these could be potentially used for b-cell differentiation either at the foregut endoderm-equivalent or the pancreatic endoderm-equivalent level (d). Last, reprogramming techniques previously developed for iPS cell generation have also been successfully used to transdifferentiate (or laterally reprogram) either liver or pancreatic acinar tissue (e) directly into insulin-producing b-cells (adapted from Orlando et al [137], with permission).…”

Section: Adult Stem Cellsmentioning

confidence: 99%

Cell Replacement Strategies Aimed at Reconstitution of the β-Cell Compartment in Type 1 Diabetes

et al. 2014

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Emerging technologies in regenerative medicine have the potential to restore the b-cell compartment in diabetic patients, thereby overcoming the inadequacies of current treatment strategies and organ supply. Novel approaches include: 1) Encapsulation technology that protects islet transplants from host immune surveillance; 2) stem cell therapies and cellular reprogramming, which seek to regenerate the depleted b-cell compartment; and 3) whole-organ bioengineering, which capitalizes on the innate properties of the pancreas extracellular matrix to drive cellular repopulation. Collaborative efforts across these subfields of regenerative medicine seek to ultimately produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes.Regenerative medicine promises to contribute to the advancement of b-cell replacement strategies through the development and implementation of microencapsulation technology, the production of insulin-producing cells either by regeneration from endogenous cells or reprogramming from nonendocrine adult cell sources, and, more recently, the exploitation of bioengineered microenvironments (1). Considering the shortage of available pancreata, the search for alternative cell sources has recently been categorized within one of the following three "Rs" of pancreatic b-cell replenishment: replacement (from stem cells or xenoislets), regeneration (from endogenous progenitor cells), and reprogramming (from nonendocrine adult cell sources) (2).The purpose of this article is to comprehensively and critically review the main regenerative medicine2based strategies that are currently being developed to treat type 1 diabetes. The first part of the article will illustrate and discuss islet encapsulation technology, which has been extensively investigated over the past 40 years (3) and represents one of the most promising regenerative medicine2based approaches to achieve immunoisolation of transplantable organs. The second part will focus on cell bioengineering, where different types of progenitor and differentiated cell sources are manipulated to ultimately yield insulin-producing cells. The last part of the article will summarize the most recent advancements in the study of the pancreatic extracellular matrix (ECM) as a platform for endocrine pancreas bioengineering. ISLET ENCAPSULATION TECHNOLOGYEncapsulation technology has been used to protect islets from the host immune system. This strategy holds the promise to allow implantation of islets without immunosuppression not only across genetically different individuals from the same species, but also across species barriers. MicroencapsulationThe first approach to immunoisolate cells consists of the microencapsulation of one to three islets per semipermeable immunoprotective capsule. The spherical configuration of these microcapsules results in a higher surface-tovolume ratio and a higher diffusion rate (4). Furthermore, microcapsules can be injected in large numbers, are durable, and are difficult to disrup...

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Cell and organ bioengineering technology as applied to gastrointestinal diseases

Cited by 41 publications

References 137 publications

Renal Bioengineering with Scaffolds Generated from Human Kidneys

Renal Bioengineering with Scaffolds Generated from Human Kidneys

Whole-Organ Tissue Engineering: No Longer Just a Dream

Cell Replacement Strategies Aimed at Reconstitution of the β-Cell Compartment in Type 1 Diabetes

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