Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids

Willemse, Jorke; Tienderen, Gilles van; Hengel, Eline V. A. van; Schurink, Ivo J.; Ven, Diana L. Van Der; Kan, Yik Y.; Ruiter, Petra E. de; Rosmark, Oskar; G, Gunilla Westergren-Thorsson; Schneeberger, Kerstin; Eerden, Bram van der; Roest, Henk P.; Spee, Bart; Laan, Lijckle van der; Jonge, Jeroen de; Verstegen, Monique M.A.

doi:10.1016/j.biomaterials.2022.121473

Cited by 47 publications

(44 citation statements)

References 70 publications

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“…However, it was also shown that there is a tissue-specific effect of the ECM hydrogels on the organoids [ 37 ]. HLECM can successfully replace BME as a tissue-specific culture substrate for ICO; therefore, we tested this liver ECM extract to augment the Dex-Ta hydrogels [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…HLECM hydrogels were prepared as previously described [ 21 ]. In short, the ECM was lyophilized (Zirbus Technology Sublimator 400) and pulverized (Retsch ZM200).…”

Section: Methodsmentioning

confidence: 99%

“…We have recently shown that BME can be replaced by a hydrogel derived from decellularized human liver ECM [ 21 ]. This hydrogel supports the initiation and culture of cholangiocyte organoids and can unlock direct clinical applications for regenerative medicine purposes [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we report on a microfluidic methodology for the controlled, high-throughput production of intrahepatic cholangiocyte organoids (ICO) and cholangiocarcinoma organoids (CCAO) in hybrid microcapsules containing decellularized liver-derived extracellular matrix [ 21 ]. In order to achieve this, primary human cholangiocyte and cholangiocarcinoma cells are encapsulated in a human liver extracellular matrix-containing dextran-tyramine microcapsules utilizing single-step enzymatic outside-in crosslinking in an off-the-shelf, reusable, flow-focusing microfluidic device.…”

Section: Introductionmentioning

confidence: 99%

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Scalable Production of Size-Controlled Cholangiocyte and Cholangiocarcinoma Organoids within Liver Extracellular Matrix-Containing Microcapsules

Tienderen

Willemse

Loo

et al. 2022

Cells

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Advances in biomaterials, particularly in combination with encapsulation strategies, have provided excellent opportunities to increase reproducibility and standardization for cell culture applications. Herein, hybrid microcapsules are produced in a flow-focusing microfluidic droplet generator combined with enzymatic outside-in crosslinking of dextran-tyramine, enriched with human liver extracellular matrix (ECM). The microcapsules provide a physiologically relevant microenvironment for the culture of intrahepatic cholangiocyte organoids (ICO) and patient-derived cholangiocarcinoma organoids (CCAO). Micro-encapsulation allowed for the scalable and size-standardized production of organoids with sustained proliferation for at least 21 days in vitro. Healthy ICO (n = 5) expressed cholangiocyte markers, including KRT7 and KRT19, similar to standard basement membrane extract cultures. The CCAO microcapsules (n = 3) showed retention of stem cell phenotype and expressed LGR5 and PROM1. Furthermore, ITGB1 was upregulated, indicative of increased cell adhesion to ECM in microcapsules. Encapsulated CCAO were amendable to drug screening assays, showing a dose-response response to the clinically relevant anti-cancer drugs gemcitabine and cisplatin. High-throughput drug testing identified both pan-effective drugs as well as patient-specific resistance patterns. The results described herein show the feasibility of this one-step encapsulation approach to create size-standardized organoids for scalable production. The liver extracellular matrix-containing microcapsules can provide a powerful platform to build mini healthy and tumor tissues for potential future transplantation or personalized medicine applications.

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Section: Resultsmentioning

confidence: 99%

“…HLECM hydrogels were prepared as previously described [ 21 ]. In short, the ECM was lyophilized (Zirbus Technology Sublimator 400) and pulverized (Retsch ZM200).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Scalable Production of Size-Controlled Cholangiocyte and Cholangiocarcinoma Organoids within Liver Extracellular Matrix-Containing Microcapsules

Tienderen

Willemse

Loo

et al. 2022

Cells

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“…Stem cells have the unique ability to differentiate into different tissue types, but they generally require specialized treatments to induce this differentiation into a particular cell type. The specific make-up of the ECM is unique to each tissue type, and the ECM has been shown to have the potential to induce and enhance the differentiation of stem cells towards the phenotype associated with the tissue source of the ECM [ 14 , 56 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ].…”

Section: Structure and Properties Of Ecmmentioning

confidence: 99%

Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering

McInnes

Möser

Chen

2022

JFB

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The multidisciplinary fields of tissue engineering and regenerative medicine have the potential to revolutionize the practise of medicine through the abilities to repair, regenerate, or replace tissues and organs with functional engineered constructs. To this end, tissue engineering combines scaffolding materials with cells and biologically active molecules into constructs with the appropriate structures and properties for tissue/organ regeneration, where scaffolding materials and biomolecules are the keys to mimic the native extracellular matrix (ECM). For this, one emerging way is to decellularize the native ECM into the materials suitable for, directly or in combination with other materials, creating functional constructs. Over the past decade, decellularized ECM (or dECM) has greatly facilitated the advance of tissue engineering and regenerative medicine, while being challenged in many ways. This article reviews the recent development of dECM for tissue engineering and regenerative medicine, with a focus on the preparation of dECM along with its influence on cell culture, the modification of dECM for use as a scaffolding material, and the novel techniques and emerging trends in processing dECM into functional constructs. We highlight the success of dECM and constructs in the in vitro, in vivo, and clinical applications and further identify the key issues and challenges involved, along with a discussion of future research directions.

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Biocompatible Human Placental Extracellular Matrix Derived Hydrogels

Gujjar,

Tyagi,

Sainger

et al. 2023

Advanced Biology

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Solubilizing extracellular matrix (ECM) materials and transforming them into hydrogels has expanded their potential applications both in vitro and in vivo. In this study, hydrogels are prepared by decellularization of human placental tissue using detergent and enzymes and by the subsequent creation of a homogenized acellular placental tissue powder (P‐ECM). A perfusion‐based decellularization approach is employed using detergent and enzymes. The P‐ECM with and without gamma irradiation is then utilized to prepare P‐ECM hydrogels. Physical and biological evaluations are conducted to assess the suitability of the P‐ECM hydrogels for biocompatibility. The decellularized tissue has significantly reduced cellular content and retains the major ECM proteins. Increasing the concentration of P‐ECM leads to improved mechanical properties of the P‐ECM hydrogels. The biocompatibility of the P‐ECM hydrogel is demonstrated through cell proliferation and viability assays. Notably, gamma‐sterilized P‐ECM does not support the formation of a stable hydrogel. Nonetheless, the use of HCl during the digestion process effectively decreases spore growth and bacterial bioburden. The study demonstrates that P‐ECM hydrogels exhibit physical and biological attributes conducive to soft tissue reconstruction. These hydrogels establish a favorable microenvironment for cell growth and the need for investigating innovative sterilization methods.

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Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids

Cited by 47 publications

References 70 publications

Scalable Production of Size-Controlled Cholangiocyte and Cholangiocarcinoma Organoids within Liver Extracellular Matrix-Containing Microcapsules

Scalable Production of Size-Controlled Cholangiocyte and Cholangiocarcinoma Organoids within Liver Extracellular Matrix-Containing Microcapsules

Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering

Biocompatible Human Placental Extracellular Matrix Derived Hydrogels

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