Regeneration and experimental orthotopic transplantation of a bioengineered kidney
Jeremy Song,Jacques P. Guyette,Sarah E. Gilpin,Gabriel Gonzalez,Joseph P. Vacanti,Harald C. Ott +5 more
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TLDR
To regenerate functional tissue, rat kidney scaffolds are seeded with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor, resulting in grafts that produced rudimentary urine in vitro when perfused through their intrinsic vascular bed.Abstract:
Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo.read more
Citations
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Journal ArticleDOI
Decellularized scaffolds as a platform for bioengineered organs.
Luis F. Tapias,Harald C. Ott +1 more
TL;DR: Many challenges remain on the way to producing an autologous, fully functional organ that can be transplanted similar to a donor organ, and this technology needs to be scaled up to human size to be of clinical relevance.
Journal ArticleDOI
Towards the development of a bioengineered uterus: comparison of different protocols for rat uterus decellularization.
Mats Hellström,R.R. El-Akouri,Carina Sihlbom,Britt-Marie Olsson,J. Lengqvist,Henrik Bäckdahl,Bengt Johansson,Michael Olausson,Suchitra Sumitran-Holgersson,Mats Brännström +9 more
TL;DR: This study shows the first available data on decellularized whole uterus, and creates new opportunities for numerous in vitro and in vivo whole-uterus tissue engineering applications.
Journal ArticleDOI
Engineered composite tissue as a bioartificial limb graft
Bernhard J. Jank,Linjie Xiong,Philipp T. Moser,Jacques P. Guyette,Xi Ren,Curtis L. Cetrulo,David A. Leonard,Leopoldo Fernandez,Shawn P. Fagan,Harald C. Ott +9 more
TL;DR: An autologous, bio-artificial graft based on native extracellular matrix and patient derived cells could be produced on demand and would not require immunosuppression after transplantation.
Journal ArticleDOI
Molecular assessment of collagen denaturation in decellularized tissues using a collagen hybridizing peptide.
Jeongmin Hwang,Boi Hoa San,Neill J. Turner,Lisa J. White,Denver M. Faulk,Stephen F. Badylak,Yang Li,S. Michael Yu +7 more
TL;DR: This work demonstrates the first investigation into the molecular denaturation of collagen in decellularized ECM enabled by a novel Collagen Hybridizing Peptide (CHP) that specifically binds to unfolded collagen chains and shows that SDS and Triton X-100 denature collagen molecules while CHAPS and SD cannot.
Journal ArticleDOI
Decellularized kidney scaffold-mediated renal regeneration.
Yaling Yu,Yingkuan Shao,Yu-Qiang Ding,Kezhi Lin,B. Chen,H.Z. Zhang,Zhao Li Na,Zhibin Wang,Jianse Zhang,Maolin Tang,Jin Mei +10 more
TL;DR: Evidence is provided that decellularized rat kidney scaffolds could be used to promote renal recovery in the treatment of chronic kidney disease by showing significant recovery of renal functions at 6 weeks post-implantation.
References
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Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart
Harald C. Ott,Thomas S Matthiesen,Saik Kia Goh,Lauren D. Black,Stefan M. Kren,Theoden I. Netoff,Doris A. Taylor +6 more
TL;DR: Eight constructs decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent a cellular valves and intact chamber geometry that could generate pump function in a modified working heart preparation.
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Tissue-engineered autologous bladders for patients needing cystoplasty
TL;DR: Engineered bladder tissues, created with autologous cells seeded on collagen-polyglycolic acid scaffolds, and wrapped in omentum after implantation, can be used in patients who need cystoplasty.
Journal ArticleDOI
Regeneration and orthotopic transplantation of a bioartificial lung
Harald C. Ott,Ben Clippinger,Claudius Conrad,Christian Schuetz,Irina Pomerantseva,Laertis Ikonomou,Darrell N. Kotton,Joseph P. Vacanti +7 more
TL;DR: Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange, and regenerated lungs into orthotopic position showed in vivo function.
Journal ArticleDOI
HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression
Tatsuo Kawai,A. Benedict Cosimi,Thomas R. Spitzer,Nina Tolkoff-Rubin,Manikkam Suthanthiran,Susan L. Saidman,Juanita Shaffer,Frederic I. Preffer,Ruchuang Ding,Vijay K. Sharma,Jay A. Fishman,Bimalangshu R. Dey,Dicken S.C. Ko,Martin Hertl,Nelson Goes,Waichi Wong,Winfred W. Williams,Robert B. Colvin,Megan Sykes,David H. Sachs +19 more
TL;DR: Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen, and it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation.
Journal ArticleDOI
Organ engineering based on decellularized matrix scaffolds
Jeremy Song,Harald C. Ott +1 more
TL;DR: A review summarizes achievements to date and discusses the role of native ECM scaffolds in organ regeneration, which provides a promising alternative to synthetic scaffolds and a foundation for regenerative efforts.
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