Modeling Human Organ Development and Diseases With Fetal Tissue–Derived Organoids

Liang, Jianqing; Li, Xinyang; Dong, Yateng; Zhao, Bing

doi:10.1177/09636897221124481

Cited by 8 publications

(5 citation statements)

References 143 publications

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“…Re-epithelialization of the endometrium is an efficient process that provides scar-free healing and repair. The extreme regenerative capacity of the endometrium is based on the presence of progenitors, located in the epithelial and stromal cell compartments of the basalis layer 18 , 19 , 20 . A previous study demonstrated that intrauterine transplantation of EEOs effectively repaired the basal layer of the endometrium in an IUA mice model and conducted the intact endometrium 7 .…”

Section: Discussionmentioning

confidence: 99%

Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration

Xu,

Cai,

Wang

et al. 2023

Cell Transplant

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Asherman’s syndrome is an endometrial regeneration disorder resulting from injury to the endometrial basal layer, causing the formation of scar tissue in the uterus and cervix. This usually leads to uterine infertility, menstrual disorders, and placental abnormalities. While stem cell therapy has shown extensive progress in repairing the damaged endometrium and preventing intrauterine adhesion, issues of low engraftment rates, rapid senescence, and the risk of tumorigenesis remain to be resolved for efficient and effective application of this technology in endometrial repair. This study addressed these challenges by developing a co-culture system to generate multi-lineage endometrial organoids (MLEOs) comprising endometrial epithelium organoids (EEOs) and endometrial mesenchymal stem cells (eMSCs). The efficacy of these MLEOs was investigated by seeding them on a biocompatible scaffold, the human acellular amniotic membrane (HAAM), to create a biological graft patch, which was subsequently transplanted into an injury model of the endometrium in rats. The results indicated that the MLEOs on the HAAM patch facilitated endometrial angiogenesis, regeneration, and improved pregnancy outcomes. The MLEOs on the HAAM patch could serve as a promising strategy for treating endometrial injury and preventing Asherman’s syndrome.

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Section: Discussionmentioning

confidence: 99%

Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration

Xu,

Cai,

Wang

et al. 2023

Cell Transplant

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“…Therefore, PSC‐derived organoids are generally naïve, resembling fetal tissues, which can be considered as excellent models for organogenesis research 53 . ESC‐derived organoids are more mature than iPSC‐derived organoids, which can be used as novel models for studying later phases of organogenesis 54,55 . However, ESCs need to be obtained from the embryo and there are many ethical issues involved (Figure 2).…”

Section: Cell Sources Of Organoidmentioning

confidence: 99%

“… 53 ESC‐derived organoids are more mature than iPSC‐derived organoids, which can be used as novel models for studying later phases of organogenesis. 54 , 55 However, ESCs need to be obtained from the embryo and there are many ethical issues involved (Figure 2 ).…”

Section: Cell Sources Of Organoidmentioning

confidence: 99%

Organoids: The current status and biomedical applications

Yang

Kung

et al. 2023

MedComm

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Organoids are three‐dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long‐term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large‐scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

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“…[35] These structures exhibit high genetic stability and expansion yield, making them excellent candidates for tissue engineering of clinically relevant-sized structures that exhibit highly predictive functions compared to their native counterpart. [23,[36][37][38] The striking cellular organization similarities to native tissues, and the possibility to obtain these cell assemblies from most tissues in the human body have made organoids one of the most promising preclinical model candidates in recent years, with great strides in the understanding of organ development, [36,[39][40][41][42] as well as human genetic and developmental pathologies. [36,38,[40][41][42][43][44][45][46][47][48][49][50] As organoids can also be obtained from primary cells (i.e., obtained from biopsies) these tissue models have also facilitated the advancement of patient specific 1 biomedical research, and enabled further understanding and treatment development of rare diseases.…”

Section: Biofabricated Modelsmentioning

confidence: 99%

“…[23,[36][37][38] The striking cellular organization similarities to native tissues, and the possibility to obtain these cell assemblies from most tissues in the human body have made organoids one of the most promising preclinical model candidates in recent years, with great strides in the understanding of organ development, [36,[39][40][41][42] as well as human genetic and developmental pathologies. [36,38,[40][41][42][43][44][45][46][47][48][49][50] As organoids can also be obtained from primary cells (i.e., obtained from biopsies) these tissue models have also facilitated the advancement of patient specific 1 biomedical research, and enabled further understanding and treatment development of rare diseases. [37,39,51] In combination with genome editing technologies [52][53][54] and other emerging biomedical tools, organoids are sure to bring about a revolution in the biomedical research field and have the potential to shape the next generation of in vitro models.…”

Section: Biofabricated Modelsmentioning

confidence: 99%

Crafting Tissue Complexity

Núñez Bernal

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The global rise in life expectancy is accompanied by an increasing prevalence of chronic diseases, posing economic burdens and impacting patients' well-being. This surge in disease incidence challenges the drug discovery pipeline, calling for the adaptation of its rules and regulations to reduce the ever-increasing failure rates of new drugs. The staggering growth of the pharmaceutical industry in the last decades, and the high expenditure required to bring new drugs to the market is set to become an unsustainable issue in the coming years. Recently, far more attention has been focused on the preclinical phase of the pipeline, where drug evaluation culminates in animal testing, the current gold standard to ensure drug safety and efficacy before human trials. A consensus on the need for more complex and predictive human disease models has emerged and become a priority for scientists and policy makers in the past decade. Biofabrication, an emerging technology-driven field, has gained prominence in biomedical research for developing advanced in vitro models. Biofabrication is “the automated generation of biologically functional products with structural organization from living cells, bioactive molecules, biomaterials, cell aggregates such as micro-tissues, or hybrid cell-material constructs, through Bioprinting or Bioassembly and subsequent tissue maturation processes”. The last decades have seen the rapid development new bioprinting modalities, opening the door to the development of architecturally complex in vitro platforms where multi-cellular and multi-material structures can be more easily created. Considering the need for more complex preclinical models to bridge the translational gap between 2D in vitro models, animal testing and clinical trials, the overarching aim of this thesis was “to develop new biofabrication approaches, encompassing 3D bioprinting technologies, powerful biological building blocks, and smart biomaterials, that facilitate the development of advanced human in vitro models with native tissue-like functionality”. This research has introduced significant advancements within the field of biofabrication for the generation of human in vitro models. Through a comprehensive exploration that tackled challenges related to fundamental bioprinting principles, the biological intricacies, and the biochemical and material property requirements of bioprinted structures to better recapitulate native tissues, the developments described here have expanded the toolkit of biofabrication approaches. By introducing novel technologies, like the pioneering, layerless volumetric bioprinting strategy, and synergizing new and existing printing approaches to harness their unique advantages, this thesis showcases a variety of functional bioprinted tissue models that enable the study of biological processes in vitro. The thorough exploration of volumetric bioprinting, distinguished by its scalability, unparalleled design freedom, compatibility with advanced biological tools, and a growing library of smart materials, charts new paths toward the creation of clinically-relevant testing platforms. The bioprinted, tissue-specific in vitro models presented here offer enhanced physiological accuracy and predictability and hold the potential to incorporate patient-specific elements for personalized medicine. The toolkit developed in here represents a significant stride in bridging the translational gap of tissue-engineered in vitro models, particularly in the context of preclinical testing. All in all, the evolving landscape of biofabricated in vitro models holds promise for innovative approaches in the future.

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Modeling Human Organ Development and Diseases With Fetal Tissue–Derived Organoids

Cited by 8 publications

References 143 publications

Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration

Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration

Organoids: The current status and biomedical applications

Crafting Tissue Complexity

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