Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine

Huang, Danyang; Gibeley, Sarah B.; Xu, Cong; Xiao, Yang; Celik, Ozgenur; Ginsberg, Henry N.; Leong, Kam W.

doi:10.1002/adfm.201909553

Cited by 32 publications

(31 citation statements)

References 259 publications

(263 reference statements)

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“…Further improvements could benefit BALMs. Although coculture of hiHEPs and HUVECs seeded through the PV allowed a better mimicking of the liver environment ( Huang et al., 2020 ), it has been very recently shown that also endothelial and biliary cell types could be derived from human iPSC and co-seeded with iPSC-derived hepatocytes in decellularized livers to form functional mini livers. The latter could be used for auxiliary transplantation in immunocompromised rats and remain functional for 4 days in vivo ( Takeishi et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies

et al. 2020

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Summary Explosion of gene therapy approaches for treating rare monogenic and common liver disorders created an urgent need for disease models able to replicate human liver cellular environment. Available models lack 3D liver structure or are unable to survive in long-term culture. We aimed to generate and test a 3D culture system that allows long-term maintenance of human liver cell characteristics. The in vitro whole-organ “Bioreactor grown Artificial Liver Model” (BALM) employs a custom-designed bioreactor for long-term 3D culture of human induced pluripotent stem cells-derived hepatocyte-like cells (hiHEPs) in a mouse decellularized liver scaffold. Adeno-associated viral (AAV) and lentiviral (LV) vectors were introduced by intravascular injection. Substantial AAV and LV transgene expression in the BALM-grown hiHEPs was detected. Measurement of secreted proteins in the media allowed non-invasive monitoring of the system. We demonstrated that humanized whole-organ BALM is a valuable tool to generate pre-clinical data for investigational medicinal products.

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Section: Discussionmentioning

confidence: 99%

An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies

et al. 2020

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“…Specifically, microgels are fabricated in microfluidic devices by the generation of polymer droplets (i.e., droplet-based microfluidics) through water/oil emulsions followed by physical or chemical crosslinking. The most frequently used geometry configurations to generate the droplets in the devices are T-junction, flow-focusing, and co-flowing (or capillary) laminar streams, which are illustrated in Figure 1C [41][42][43][44]. Microgels are especially attractive as cell carriers, because their large surface-to-volume ratio promotes efficient mass transport and enhances cell-matrix interactions, but it is important to notice that cell microencapsulation requires a polymer network that ensures cell viability during microgel preparation and adequate crosslinking chemistry to form a polymer network [45].…”

Section: Microfluidicsmentioning

confidence: 99%

“…Encapsulation of MSCs in polymeric microgels is an excellent approach to improving cell persistence and immunomodulation [61]. Cell therapies based on MSCs are particularly interesting in ameliorating immune-related diseases and dysregulations, but they are limited due to short in vivo persistence [44,45,61,62]. Mao et al [61] reported the encapsulation of MSCs in alginate-polylysine microgels using a microfluidic device.…”

Section: Figurementioning

confidence: 99%

Emerging Biofabrication Techniques: A Review on Natural Polymers for Biomedical Applications

2021

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Natural polymers have been widely used for biomedical applications in recent decades. They offer the advantages of resembling the extracellular matrix of native tissues and retaining biochemical cues and properties necessary to enhance their biocompatibility, so they usually improve the cellular attachment and behavior and avoid immunological reactions. Moreover, they offer a rapid degradability through natural enzymatic or chemical processes. However, natural polymers present poor mechanical strength, which frequently makes the manipulation processes difficult. Recent advances in biofabrication, 3D printing, microfluidics, and cell-electrospinning allow the manufacturing of complex natural polymer matrixes with biophysical and structural properties similar to those of the extracellular matrix. In addition, these techniques offer the possibility of incorporating different cell lines into the fabrication process, a revolutionary strategy broadly explored in recent years to produce cell-laden scaffolds that can better mimic the properties of functional tissues. In this review, the use of 3D printing, microfluidics, and electrospinning approaches has been extensively investigated for the biofabrication of naturally derived polymer scaffolds with encapsulated cells intended for biomedical applications (e.g., cell therapies, bone and dental grafts, cardiovascular or musculoskeletal tissue regeneration, and wound healing).

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“…12 Several excellent reviews describing biomaterials and advanced techniques, such as 3D printing and microfluidics, for liver disease modeling and treatment are already available. [13][14][15][16] For example, Morais et al 13 systematically summarized a wide range of natural and synthetic biomaterials in various forms such as hydrogels or solid scaffolds for liver regeneration. Meanwhile, different 3D-printing strategies for liver tissue engineering and regeneration have also been discussed in the review.…”

Section: Introductionmentioning

confidence: 99%

Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure

et al. 2021

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Liver failure is a lethal condition with hepatocellular dysfunction, and liver transplantation is presently the only effective treatment. However, due to the limited availability of donors and the potential immune rejection, novel therapeutic strategies are actively sought to restore the normal hepatic architectures and functions, especially for livers with inherited metabolic dysfunctions or chronic diseases. Although the conventional cell therapy has shown promising results, the direct infusion of hepatocytes is hampered by limited hepatocyte sources, poor cell viability, and engraftment. Hence, this review mainly highlights the role of stem cells and progenitors as the alternative cell source and summarizes the potential approaches based on tissue engineering to improve the delivery efficiency of cells. Particularly, the underlying mechanisms for cell therapy using stem cells and progenitors are discussed in two main aspects: paracrine effect and cell differentiation. Moreover, tissue-engineering approaches using cell aggregates and decellularized liver scaffolds for bioengineering of functional hepatic constructs are discussed and compared in terms of the potential to replicate liver physiological structures. In the end, a potentially effective strategy combining the premium advantages of stem cell aggregates and decellularized liver scaffolds is proposed as the future direction of liver tissue engineering and regeneration.

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Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine

Cited by 32 publications

References 259 publications

An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies

An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies

Emerging Biofabrication Techniques: A Review on Natural Polymers for Biomedical Applications

Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure

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