Bio-engineered endocrine pancreas based on decellularized pancreatic matrix and mesenchymal stem cell/islet cell coculture

Conrad, Claudius; Schuetz, Christian; Clippinger, Benjamin; Vacanti, Joseph P.; Markmann, James F.; Ott, Harald C.

doi:10.1016/j.jamcollsurg.2010.06.161

Cited by 23 publications

(14 citation statements)

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“…The novel concept of whole organ perfusion decellularization has been described recently to generate native ECM scaffolds from complex organs such as heart [16–19], liver [20–23], lung [24–29], kidney [30–32] and more recently pancreas [33–36]. Whole organ acellular matrices provide an attractive scaffold for the repopulation with cells for an engineered tissue/organ because of the physiological resemblance of the original tissue, including intact 3D anatomical architecture, preserved spatial array of ECM components, vascular network, and biomechanical properties.…”

Section: Introductionmentioning

confidence: 99%

Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

et al. 2013

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Approximately 285 million people worldwide suffer from diabetes, with insulin supplementation as the most common treatment measure. Regenerative medicine approaches such as a bioengineered pancreas has been proposed as potential therapeutic alternatives. A bioengineered pancreas will benefit from the development of a bioscaffold that supports and enhances cellular function and tissue development. Perfusion-decellularized organs are a likely candidate for use in such scaffolds since they mimic compositional, architectural and biomechanical nature of a native organ. In this study, we investigate perfusion-decellularization of whole pancreas and the feasibility to recellularize the whole pancreas scaffold with pancreatic cell types. Our result demonstrates that perfusion-decellularization of whole pancreas effectively removes cellular and nuclear material while retaining intricate three-dimensional microarchitecture with perfusable vasculature and ductal network and crucial extracellular matrix (ECM) components. To mimic pancreatic cell composition, we recellularized the whole pancreas scaffold with acinar and beta cell lines and cultured up to 5 days. Our result shows successful cellular engraftment within the decellularized pancreas, and the resulting graft gave rise to strong up-regulation of insulin gene expression. These findings support biological utility of whole pancreas ECM as a biomaterials scaffold for supporting and enhancing pancreatic cell functionality and represent a step toward bioengineered pancreas using regenerative medicine approaches.

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Section: Introductionmentioning

confidence: 99%

Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

et al. 2013

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“…Even though great advances have been made in small animal models, the field is still far from achieving the regeneration of a solid organ with a function similar to cadaveric organs. The same concepts used to bioengineer the organs mentioned above could be applied to produce other organs or tissues such as the esophagus [61-63], small bowel [63-65], pancreas [66,67], trachea [68], muscle or composite tissue grafts. Research efforts in the coming years should focus on specific goals (Table 1) to standardize the decellularization process, manipulate stem cells as desired, preserve scaffolds and organs, evaluate the immune response and reach the next mile-stone: the transplantation of bioengineered organs in a large animal model.…”

Section: Discussionmentioning

confidence: 99%

Decellularized scaffolds as a platform for bioengineered organs

Tapias

Ott

2014

Current Opinion in Organ Transplantation

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112

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PURPOSE OF REVIEW Patients suffering from end-stage organ failure requiring organ transplantation face donor organ shortage and adverse effect of chronic immunosuppression. Recent progress in the field of organ bioengineering based on decellularized organ scaffolds and patient derived cells holds great promise to address these issues. RECENT FINDINGS Perfusion-decellularization is the most consistent method to obtain decellularized whole-organ scaffolds to serve as a platform for organ bioengineering. Important advances have occurred in organ bioengineering using decellularized scaffolds in small animal models. However, the function exhibited by bioengineered organs has been rudimentary. Pluripotent stem cells seem hold promise as the ideal regenerative cells to be used with this approach but the techniques to effectively and reliably manipulate their fate are still to be discovered. Finally, this technology needs to be scaled up to human size to be of clinical relevance. SUMMARY The search for alternatives to allogeneic organ transplantation continues. Important milestones have been achieved in organ bioengineering with the use of decellularized scaffolds. However, many challenges remain on the way to producing an autologous, fully functional organ that can be transplanted similar to a donor organ.

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“…To our knowledge, in the same year, Ott's lab proposed for the first time a rat pancreatic whole pancreas scaffold (obtained via detergent perfusion) afterwards seeded with human islets and supporting human MSCs. Results were very fascinating showing effective tridimensional growth of cells on the matrix with good response to glucose stimula [121]. Both these studies have shown important starting lines for the use of this technology to produce a functional bioengineered pancreas.…”

Section: Cell-on-scaffold Technology Toward Bioartificial Pancreas: Smentioning

confidence: 99%

Bioengineering the Pancreas: Cell-on-Scaffold Technology

Peloso¹,

Citro²,

Oldani³

et al. 2017

Scaffolds in Tissue Engineering - Materials, Technologies and Clinical Applications

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Nowadays, type I diabetes mellitus is a pathology afflicting millions of people globally with a dramatic assessment in the next future. Current treatments including exogenous insulin, pancreas transplantation and islets transplantation, are not free from important lifelong side effects. In the last decade, tissue engineering and regenerative medicine have shown encouraging results about the possibility to produce a functional bioengineered pancreas. Among many technologies, decellularization offers the opportunity to produce an organ-specific acellular matrix that could subsequently repopulate with endocrine cellular population. Herein, we aim to review the state-of-art and this technology highlighting the diabetes burden for the healthcare system and the major achievements toward the manufacturing of a bioengineered pancreas obtained by cell-on-scaffold technology.

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Bio-engineered endocrine pancreas based on decellularized pancreatic matrix and mesenchymal stem cell/islet cell coculture

Cited by 23 publications

References 0 publications

Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering

Decellularized scaffolds as a platform for bioengineered organs

Bioengineering the Pancreas: Cell-on-Scaffold Technology

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