Patch grafting, strategies for transplantation of organoids into solid organs such as liver

Zhang, Wencheng; Lanzoni, Giacomo; Hani, Homayoun; Overi, Diletta; Cardinale, Vincenzo; Simpson, Sean; Pitman, Wendy A.; Allen, Amanda; Yi, Xin; Wang, Xicheng; Gerber, David A.; Prestwich, Glenn D.; Lozoya, Oswaldo A.; Gaudio, Eugenio; Alvaro, Domenico; Tokaz, Debra; Domínguez‐Bendala, Juan; Adin, Christopher A.; Piedrahita, Jorge; Mathews, Kyle G.; Sethupathy, Praveen; Carpino, Guido; He, Zhiying; Wauthier, Eliane; Reíd, Lola M.

doi:10.1016/j.biomaterials.2021.121067

Cited by 23 publications

(29 citation statements)

References 62 publications

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“…The in vivo data revealed that engrafted organoids strongly correlated with matrix-metalloproteinases (MMPs), especially MMP2 (secreted isoforms). This novel patch strategy for liver organoids provides great hope for stem-cell-derived organoid construction for solid organs [ 68 ]. A study developed an innovative strategy for one-step synthesis of composite hydrogel capsules (CHCs, composed of a fibrin hydrogel core and an alginate-chitosan composite shell), which boosted hiPSCs-derived liver organoids using an oil-free droplet microfluidic system.…”

Section: Discussionmentioning

confidence: 99%

Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review

Yue

Liu

et al. 2022

Gels

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Organoids are novel in vitro cell culture models that enable stem cells (including pluripotent stem cells and adult stem cells) to grow and undergo self-organization within a three-dimensional microenvironment during the process of differentiation into target tissues. Such miniature structures not only recapitulate the histological and genetic characteristics of organs in vivo, but also form tissues with the capacity for self-renewal and further differentiation. Recent advances in biomaterial technology, particularly hydrogels, have provided opportunities to improve organoid cultures; by closely integrating the mechanical and chemical properties of the extracellular matrix microenvironment, with novel synthetic materials and stem cell biology. This systematic review critically examines recent advances in various strategies and techniques utilized for stem-cell-derived organoid culture, with particular emphasis on the application potential of hydrogel technology in organoid culture. We hope this will give a better understanding of organoid cultures for modelling diseases and tissue engineering applications.

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Section: Discussionmentioning

confidence: 99%

Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review

Yue

Liu

et al. 2022

Gels

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“…These include cell sheet engineering technologies that involve attachment of a cell sheet prepared ex vivo to the surface of the liver and able to provide some functions to overcome deficits ( Kikuchi and Okano, 2005 ; Tatsumi and Okano, 2017 ). The more powerful approach has been use of biomaterials supportive of stemness traits of the donor cells ( Lozoya et al, 2011 ) in conjunction with injection grafting ( Turner et al, 2013 ) or patch grafting ( Zhang et al, 2021 ), strategies that enable transplantation of large numbers of cells or of organoids that can correct major disease states. Moreover, they have proven successful for engraftment even in normal liver conditions, thus enabling avoidance of the requirements for a cellular vacuum created by a genetic condition or drug.…”

Section: Mouse Models For Studying Liver Cell Transplantation In Trea...mentioning

confidence: 99%

Mouse Models of Liver Parenchyma Injuries and Regeneration

Zhang

Qiu

et al. 2022

Front. Cell Dev. Biol.

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Mice have genetic and physiological similarities with humans and a well-characterized genetic background that is easy to manipulate. Murine models have become the most favored, robust mammalian systems for experimental analyses of biological processes and disease conditions due to their low cost, rapid reproduction, a wealth of mouse strains with defined genetic conditions (both native ones as well as ones established experimentally), and high reproducibility with respect to that which can be done in experimental studies. In this review, we focus on murine models for liver, an organ with renown regenerative capacity and the organ most central to systemic, complex metabolic and physiological functions for mammalian hosts. Establishment of murine models has been achieved for all aspects of studies of normal liver, liver diseases, liver injuries, and regenerative repair mechanisms. We summarize key information on current mouse systems that partially model facets of clinical scenarios, particularly those associated with drug-induced acute or chronic liver injuries, dietary related, non-alcoholic liver disease (NAFLD), hepatitis virus infectious chronic liver diseases, and autoimmune hepatitis (AIH). In addition, we also include mouse models that are suitable for studying liver cancers (e.g., hepatocellular carcinomas), the aging process (senescence, apoptosis), and various types of liver injuries and regenerative processes associated with them.

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“…We isolated pBTSCs from porcine biliary trees and generated organoids by protocols established previously for human stem/progenitors 45 . The cells were maintained in serum-free Kubota's Medium supplemented with 0.1% hyaluronans, conditions proven successful for ex vivo maintenance of stem/progenitor traits in BTSCs, HpSCs, and HBs 43 .…”

Section: Ex Vivo Evidence Of Multipotency Of Pbtsc Stem/progenitorsmentioning

confidence: 99%

“…To confirm further the multipotent differentiation potential of pBTSCs, we used patch grafting methods described previously to transplant organoids prepared from GFP+ transgenic pigs onto the liver versus pancreas of wild type pigs 45 . Patch grafting, a novel form of transplantation of cells to solid organs, resulted in engraftment of donor cells throughout much of the liver (or pancreas) within a week 45 . It occurred in two phases: a remodeling phase in the 7-10 days post-transplantation, followed by a differentiation phase in the next 1-2 weeks of donor cells transitioning into mature cells.…”

Section: In Vivo Studies Providing Evidence Of Multipotency Of Porcin...mentioning

confidence: 99%

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A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs versus humans

Reíd¹,

Zhang²,

Lanzoni³

et al. 2022

Preprint

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A network of co-hepato/pancreatic stem/progenitors exists postnatally in the intrahepatic, extrahepatic and intrapancreatic biliary trees of pigs and humans and found to support hepatic and pancreatic regeneration throughout life. The stem/progenitors have genetic signatures in liver/pancreas-related RNA-seq data based on Correlation, hierarchical clustering, KEGG and Short Time-series Expression Miner (STEM) analyses. Representative phenotypic traits are expression of pluripotency genes (SOX2, OCT4, KLF4), endodermal transcription factors (SOX9, SOX17, PDX1, NGN3), other stem cell traits (NCAM, EpCAM, BMI-1, CD44), and proliferation biomarkers (Ki67). Stem/progenitor niches in vivo are in peribiliary glands (PBGs) throughout the intrahepatic and extrahepatic biliary tree, in duodenal submucosal glands (Brunner’s Glands), and in pancreatic duct glands (PDGs). The highest numbers of niches in humans are in PBGs in the hepato/pancreatic common duct, a duct missing in pigs; by contrast, the highest numbers in pigs are in Brunner’s Glands and in a subset of PDGS, those nearest to the duodenum. Elsewhere in PDGs in the porcine pancreas, and in all PDGs in the human pancreas, are found only committed unipotent and bipotent progenitors. Multipotentiality of the stem/progenitors was indicated by their ability to yield hepatic versus pancreatic fates under distinct ex vivo conditions or in vivo when organoids of them were transplanted onto liver versus pancreas using patch grafting strategies. The findings establish pigs as logical hosts for translational/preclinical studies assessing grafts of organoids of the biliary tree’s co-hepato/pancreatic stem cells as cell therapies for diseases and dysfunctions in liver and pancreas both for humans and for veterinary animals.

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Patch grafting, strategies for transplantation of organoids into solid organs such as liver

Cited by 23 publications

References 62 publications

Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review

Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review

Mouse Models of Liver Parenchyma Injuries and Regeneration

A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs versus humans

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