Methods for vascularization and perfusion of tissue organoids

Strobel, Hannah A.; Moss, Sarah M.; Hoying, James B.

doi:10.1007/s00335-022-09951-2

Cited by 11 publications

(7 citation statements)

References 101 publications

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“…The development of 3D in vitro tumor models for medical and pharmaceutical research is currently thriving. [16][17][18] However, these models mostly lack either mature vasculature systems or an appropriate ECM that supports the 3D microenvironment, impeding the effective evaluation of endovascular interventional therapies. Perfusable tumor spheroid/organoid models with large main channel and self-organized capillary-like structures have been reported with enhanced penetrability and substance exchange capability to facilitate 3D tissue regeneration for drug development.…”

Section: Discussionmentioning

confidence: 99%

“…Many vascularized tumor models utilize bottom-up selfassembly approaches to promote angiogenesis or vasculogenesis inside organoids, but the spontaneously formed capillary networks lack mature vascular organizations and functional perfusion capability. [16][17][18] The top-down pre-patterning approaches generally involve the employment of bioprinting or microfabrication techniques to create pre-defined channels in hydrogels, but these approaches face difficulty in reproducing the complex vasculature systems of varying sizes and the surrounding matrix in tumors. [19][20][21] In this regard, organ decellularization followed by recellularization may represent an ideal top-down technique to circumvent this obstacle by providing a three-dimensional (3D) template composed of organspecific vascular structures and an extracellular matrix (ECM) to grow tumors for interventional tests.…”

Section: Introductionmentioning

confidence: 99%

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Engineering orthotopic tumor spheroids with organ-specific vasculatures for local chemoembolization evaluation

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engineering orthotopic tumor spheroids with organ-specific vasculatures for local chemoembolization evaluation

et al. 2023

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“…Current techniques to vascularize organoids mainly depend on in vivo engraftment into an immune-deficient host such as NSG immunodeficient mice model, coculturing with endothelial cells (ECs) or mesodermal progenitor cells (MPCs) or gene editing to manipulate cells in organoids into adopting an endothelial fate [Birey et al, 2017;Mansour et al, 2018;Strobel et al, 2022]. Immune cells are also indispensable when modeling diseases such as cancer, viral infections, and autoimmune diseases.…”

Section: Limitations Of Existing Organoid Technologymentioning

confidence: 99%

Give them vasculature and immune cells – how to fill the gap of organoids

Yip¹,

Wang²,

Sugimura³

2023

Cells Tissues Organs

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Valid and relevant models are critical for research to have biological relevance or proceed in the right path. As well-established 2D cell cultures lack niches and cues and rodent models differ in species, 3D organoids emerged as a powerful platform for research. Cultured in vitro from stem cells, organoids are heterogeneous in cells and closely resemble the in vivo settings. Organoids also recapitulate the unique human features if cultured from a human source and are subject to genetic modification. However, one type of organoid possesses only a limited selection of cells. In particular, the absence of vasculature and immune cells restricts the organoids from nutrition, cues, or critical interactions, undermining the validity of organoids as physiological or pathological models. To fill the current gap, there is an urgent need to provide organoids with vasculature and immune cells. In this paper, we review the methods to generate physiological and pathological organoid models and summarize ways to vascularize or immunize them. Our discussion continues with some advantages and disadvantages of each method and some emerging solutions to current problems.

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“…It may result in atypical physiology of the organoid compared to the organ to be modeled. Advances in different strategies to vascularize organoids are reviewed by Strobel et al, 2022 . Furthermore, using different sources to establish organoid cultures, the heterogeneity of progenitors and differentiated cells may affect organoid formation that not necessarily corresponds to the in vivo counterparts.…”

Section: Modeling Organoids To Understand Organ Formationmentioning

confidence: 99%

Recombinant Limb Assay as in Vivo Organoid Model

García-García

Garay-Pacheco

Marín-Llera

et al. 2022

Front. Cell Dev. Biol.

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Organ formation initiates once cells become committed to one of the three embryonic germ layers. In the early stages of embryogenesis, different gene transcription networks regulate cell fate after each germ layer is established, thereby directing the formation of complex tissues and functional organs. These events can be modeled in vitro by creating organoids from induced pluripotent, embryonic, or adult stem cells to study organ formation. Under these conditions, the induced cells are guided down the developmental pathways as in embryonic development, resulting in an organ of a smaller size that possesses the essential functions of the organ of interest. Although organoids are widely studied, the formation of skeletal elements in an organoid model has not yet been possible. Therefore, we suggest that the formation of skeletal elements using the recombinant limb (RL) assay system can serve as an in vivo organoid model. RLs are formed from undissociated or dissociated-reaggregated undifferentiated mesodermal cells introduced into an ectodermal cover obtained from an early limb bud. Next, this filled ectoderm is grafted into the back of a donor chick embryo. Under these conditions, the cells can receive the nascent embryonic signals and develop complex skeletal elements. We propose that the formation of skeletal elements induced through the RL system may occur from stem cells or other types of progenitors, thus enabling the study of morphogenetic properties in vivo from these cells for the first time.

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Methods for vascularization and perfusion of tissue organoids

Cited by 11 publications

References 101 publications

Engineering orthotopic tumor spheroids with organ-specific vasculatures for local chemoembolization evaluation

Engineering orthotopic tumor spheroids with organ-specific vasculatures for local chemoembolization evaluation

Give them vasculature and immune cells – how to fill the gap of organoids

Recombinant Limb Assay as in Vivo Organoid Model

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