Xenografted tissue models for the study of human endometrial biology

Kuokkanen, Satu; Zhu, Liyin; Pollard, Jeffrey W.

doi:10.1016/j.diff.2017.11.004

Cited by 9 publications

(5 citation statements)

References 58 publications

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“…The xenograft mouse model provides an alternative model for the study of menstrual physiology and pathology (extensively reviewed in Kuokkanen et al 2017). Human functional endometrium is transplanted into immunodeficient mice (Fig.…”

Section: Xenograft Mouse Modelmentioning

confidence: 99%

HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium

et al. 2021

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The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.

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Section: Xenograft Mouse Modelmentioning

confidence: 99%

HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium

et al. 2021

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“…In the surface, the mucosa is made up of several layers of epithelial cells overlying a fibrocollagenous stroma called the stratum functionalis [43]. This stromal layer contains various cell types, such as fibroblasts, glandular epithelial cells, and immune cells [44]. Underneath the stromal layer is the stratum basale, which is adjacent to the myometrium; endometrial stem cells are located within the stratum basale, which remains in place after menstrual shedding [45].…”

Section: Discussionmentioning

confidence: 99%

3D stem cell-laden artificial endometrium: successful endometrial regeneration and pregnancy

Park

Kim

et al. 2021

Biofabrication

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Thin endometrium lining or severe endometrial injury which may occur during artificial abortion can cause defective endometrial receptivity and subsequent infertility. Therefore, much effort has been devoted toward regenerating thin or damaged endometrial lining by applying multiple types of stem cells. Even though there are some positive preliminary outcomes, repairing the injured endometrium with stem cells is considerably challenging, due to the lack of an adequate microenvironment for the administrated stem cells within the tissues and subsequent poor therapeutic efficiency. In this context, as an alternative, we fabricated a 3D stem cell-laden artificial endometrium by incorporating several biodegradable biomaterials (collagen and hyaluronic acid) and multiple cellular components of endometrium (endometrial stem cells, stromal cells, and vessel cells) to properly recapitulate the multicellular microenvironment and multilayered structure. Agarose was used as an inert filler substrate to enhance the mechanical integrity of the three-layered artificial endometrium. Various mechanical characteristics, such as morphology, compression properties, swelling, and viscosity, have been evaluated. Various biological features, such as steroid hormone responsiveness, specific endometrial cell-surface marker expressions, and the secretion of multiple growth factors and steroid hormones, as well as the viability of encapsulated endometrial cells are relatively well maintained within the artificial endometrium. More importantly, severe tissue injuries were significantly relieved by transplanting our 3D artificial endometrium into endometrial ablation mice. Remarkably, artificial endometrium transplantation resulted in a successful pregnancy with subsequent live birth without any morphological or chromosomal abnormalities.

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“…More importantly, most conventional in vitro culture models for female reproductive organs fail to mimic in vivo physiological conditions, including their multicellular complexity of the tissues. For example, the endometrial layer contains multiple cell types, such as fibroblasts, vascular epithelial cells, immune cells, and endometrial stem cells [46]. In this context, we overcame the limitations of existing in vitro models for the female reproductive tract by establishing an endometrial chamber that integrated multiple cellular components of the human endometrium, such as endometrial stem cells, stromal cells, and vascular endothelial cells, with several biodegradable natural polymers (agarose, collagen, agarose and hyaluronic acid) (figures 2(A)-(D)).…”

Section: Discussionmentioning

confidence: 99%

Development of a novel dual reproductive organ on a chip: recapitulating bidirectional endocrine crosstalk between the uterine endometrium and the ovary

Park¹,

Kim²,

Lee³

et al. 2020

Biofabrication

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Conventional 2D or even 3D in vitro culture models for human reproductive organs cannot properly recapitulate the bidirectional endocrine crosstalk between the uterine endometrium and the ovary. This crosstalk is essential for maintaining the various physiological features and functions of each tissue. Moreover, most in vitro models for the female reproductive tract also fail to mimic its multicellular structure. We therefore developed a novel ‘dual reproductive organ on a chip’ that reflects the bidirectional endocrine cross-talk and the complex multicellular structures by integrating various cellular components of both the human uterine endometrium and the ovary with several biodegradable natural polymers. Indeed, the bidirectional endocrine crosstalk between these two tissues is achieved through media sharing between channels, and it can markedly improve the viability of loaded cells within each chamber of the chip platform. In addition, we also identified a reliable reproductive toxicity marker, SERPINB2, which is significantly increased in response to various toxic exposures in both endometrial and ovarian follicular cells. Based on these findings, we next established a SERPINB2 luciferase reporter system that was specifically designed for detecting and quantifying the toxicity of certain substances. By introducing this SERPINB2 luciferase reporter system into the loaded cells within the chip platform, we ultimately developed an effective ‘dual reproductive organ-on-chip’ that was successfully used to predict the reproductive toxicity of various hazardous materials.

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Xenografted tissue models for the study of human endometrial biology

Cited by 9 publications

References 58 publications

HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium

HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium

3D stem cell-laden artificial endometrium: successful endometrial regeneration and pregnancy

Development of a novel dual reproductive organ on a chip: recapitulating bidirectional endocrine crosstalk between the uterine endometrium and the ovary

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