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使用诱导多能干细胞衍生细胞制备用于临床相关应用的个性化骨类器官。

Personalized bone organoid using iPSC-derived cells for clinically relevant applications.

作者信息

Gao Qi, Teissier Victoria, Zhu Wenjuan, Makarcyzk Meagan J, Shinohara Issei, Murayama Masatoshi, Susuki Yosuke, Chow Simon Kwoon-Ho, Bunnell Bruce A, Wu Joy, Lin Hang, Goodman Stuart B

机构信息

Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94304, USA.

Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

出版信息

Res Sq. 2024 Dec 13:rs.3.rs-5349885. doi: 10.21203/rs.3.rs-5349885/v1.

Abstract

Patient-specific induced pluripotent stem cells (iPSCs)-based modeling potentially recapitulates the pathology and mechanisms more faithfully than cell line models and general animal models. Utilizing iPSC-derived cells for personalized bone formation research offers a powerful tool to better understand the role of individual differences in bone health and disease and provide more precise information for personalized bone regeneration therapies. Here we generated iPSC-derived mesenchymal progenitor cells (iMPCs), endothelial cells (iECs), and macrophages (iMØ), from different donors. Cellular markers, pluripotency properties, and immune regulatory properties were investigated. To replicate bone regeneration, we utilize different iPSC models and co-cultured three distinct cell types (iMPCs, iECs, and iMØ) in a 3D in vitro model derived from the same donor. Cells from different donors exhibited patient-specific characteristics and different regenerative capacities. Our study suggests that cells differentiated from iPSCs can be used to anticipate the effectiveness of cell-based therapies for personalized tissue regeneration.

摘要

基于患者特异性诱导多能干细胞(iPSC)的模型可能比细胞系模型和一般动物模型更忠实地重现病理和机制。利用iPSC衍生细胞进行个性化骨形成研究,为更好地理解个体差异在骨骼健康和疾病中的作用提供了一个强大的工具,并为个性化骨再生治疗提供更精确的信息。在这里,我们从不同供体中生成了iPSC衍生的间充质祖细胞(iMPC)、内皮细胞(iEC)和巨噬细胞(iMØ)。研究了细胞标志物、多能性特性和免疫调节特性。为了复制骨再生,我们利用不同的iPSC模型,并在来自同一供体的3D体外模型中共培养三种不同的细胞类型(iMPC、iEC和iMØ)。来自不同供体的细胞表现出患者特异性特征和不同的再生能力。我们的研究表明,从iPSC分化而来的细胞可用于预测基于细胞的个性化组织再生疗法的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edaa/11661298/96b3e9f39a3a/nihpp-rs5349885v1-f0001.jpg

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