Organoid and organoid extracellular vesicles for osteoporotic fractures therapy: Current status and future perspectives

Liu, Han; Su, Jiacan

doi:10.1002/inmd.20230011

Cited by 20 publications

(5 citation statements)

References 52 publications

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“…The organoid technology has revolutionized approaches for tumor studies as well as personalized medicine. , Heterogeneity in tumor involves complicated effects coming not only from multiple types of cells but also from noncellular ECM elements, which collectively shape tumor progression. Various biomaterials have been utilized to develop in vitro 3D tumor organoid models, although there has been still no gold standard formulation of mimicking ECM optimally.…”

Section: Discussionmentioning

confidence: 99%

Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment

Xu,

Li,

Wang

et al. 2024

ACS Appl. Mater. Interfaces

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The current research models of breast cancer are usually limited in their capacity to recapitulate the tumor microenvironment in vitro. The lack of an extracellular matrix (ECM) oversimplifies cell−cell or cell−ECM cross-talks. Moreover, the lack of tumor-associated macrophages (TAMs), that can comprise up to 50% of some solid neoplasms, poses a major problem for recognizing various hallmarks of cancer. To address these concerns, a type of direct breast cancer cells (BCCs)−TAMs coculture organoid model was well developed by a sequential culture method in this study. Alginate cryogels were fabricated with appropriate physical and mechanical properties to serve as an alternative ECM. Then, our previous experience was leveraged to polarize TAMs inside of the cryogels for creating an in vitro immune microenvironment. The direct coculture significantly enhanced BCCs organoid growth and cancer aggressive phenotypes, including the stemness, migration, ECM remodeling, and cytokine secretion. Furthermore, transcriptomic analysis and protein−protein interaction networks implied certain pathways (PI3K-Akt pathway, MAPK signaling pathway, etc.) and targets (TNF, PPARG, TLR2, etc.) during breast cancer progression in a TAM-leading immune microenvironment. Future studies to advance treatment strategies for BCC patients may benefit from using this facile model to reveal and target the interactions between cancer signaling and the immune microenvironment.

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Section: Discussionmentioning

confidence: 99%

Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment

Xu,

Li,

Wang

et al. 2024

ACS Appl. Mater. Interfaces

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“…Currently, EVs can be divided into BEVs, MEVs, and EVs from plants (Cong et al., 2022). We have also defined organoid‐derived EVs as OEVs, a type of three‐dimensionally cultured MEVs, and proposed the concept of a third‐generation gut‐bone axis, which could regulate bone metabolism based on intestinal OEVs (Liu et al., 2023, Liu & Su, 2023). In addition, PEVs have also begun to be applied to the regulation of bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

Synthetic biology‐based bacterial extracellular vesicles displaying BMP‐2 and CXCR4 to ameliorate osteoporosis

Liu,

Song,

Zhang

et al. 2024

J of Extracellular Vesicle

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Osteoporosis (OP) is a systematic bone disease characterized by low bone mass and fragile bone microarchitecture. Conventional treatment for OP has limited efficacy and long‐term toxicity. Synthetic biology makes bacterial extracellular vesicle (BEVs)‐based therapeutic strategies a promising alternative for the treatment of OP. Here, we constructed a recombinant probiotics Escherichia coli Nissle 1917‐pET28a‐ClyA‐BMP‐2‐CXCR4 (ECN‐pClyA‐BMP‐2‐CXCR4), in which BMP‐2 and CXCR4 were overexpressed in fusion with BEVs surface protein ClyA. Subsequently, we isolated engineered BEVs‐BMP‐2‐CXCR4 (BEVs‐BC) for OP therapy. The engineered BEVs‐BC exhibited great bone targeting in vivo. In addition, BEVs‐BC had good biocompatibility and remarkable ability to promote osteogenic differentiation of BMSCs. Finally, the synthetic biology‐based BEVs‐BC significantly prevented the OP in an ovariectomized (OVX) mouse model. In conclusion, we constructed BEVs‐BC with both bone‐targeting and bone‐forming in one‐step using synthetic biology, which provides an effective strategy for OP and has great potential for industrialization.

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“…Bone organoids have some specific functions of bone, which can be used for bone biological mechanism research, 49 , 50 drug screening and bone tissue regeneration and repair. 51 , 52 From the perspective of differentiation regulation, bone formation has a long‐range nature, and the cells are not exactly the same in different time profiles.…”

Section: Introductionmentioning

confidence: 99%

Organoid assessment technologies

Gu,

Zhang,

et al. 2023

Clinical & Translational Med

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Despite enormous advances in the generation of organoids, robust and stable protocols of organoids are still a major challenge to researchers. Research for assessing structures of organoids and the evaluations of their functions on in vitro or in vivo is often limited by precision strategies. A growing interest in assessing organoids has arisen, aimed at standardizing the process of obtaining organoids to accurately resemble human‐derived tissue. The complex microenvironment of organoids, intricate cellular crosstalk, organ‐specific architectures and further complicate functions urgently quest for high‐through schemes. By utilizing multi‐omics analysis and single‐cell analysis, cell‐cell interaction mechanisms can be deciphered, and their structures can be investigated in a detailed view by histological analysis. In this review, we will conclude the novel approaches to study the molecular mechanism and cell heterogeneity of organoids and discuss the histological and morphological similarity of organoids in comparison to the human body. Future perspectives on functional analysis will be developed and the organoids will become mature models.

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Organoid and organoid extracellular vesicles for osteoporotic fractures therapy: Current status and future perspectives

Cited by 20 publications

References 52 publications

Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment

Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment

Synthetic biology‐based bacterial extracellular vesicles displaying BMP‐2 and CXCR4 to ameliorate osteoporosis

Organoid assessment technologies

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