Human fibroblasts facilitate the generation of iPSCs-derived mammary-like organoids.
Human fibroblasts facilitate the generation of iPSCs-derived mammary-like organoids.
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DOI：
10.1186/s13287-022-03023-7
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发表时间：
2022-07-28
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
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乳腺癌是世界范围内女性最常见的恶性肿瘤，其治疗主要依赖于乳房切除术。乳房切除术后的患者遭受残缺的身体形象，自尊和生活质量。乳房切除术后乳房再造可以改善患者的心理社会健康。虽然硅胶和脂肪已被广泛用于乳房再造，但它们具有明显的局限性。我们的研究旨在建立一种改进的人类诱导多能干细胞（iPSCs）乳房重建方法。我们使用两步法从iPSC诱导乳腺样器官（MLO），并应用转录组测序来分析从胚状体（mEB）到MLO发育过程中的基因表达谱。此外，我们评估了成纤维细胞系HFF（人包皮成纤维细胞）对MLO的大小和形态的体外影响，并探讨了HFF对MLO再生率的体内影响。MLO具有与正常乳腺相似的基因表达谱和形态发生。此外，HFF的加入增加了分支比和类器官直径，并促进体外MLO中多细胞层导管样结构的形成。最后，将MLO原位移植到NSG小鼠的透明乳腺fad垫显示HFF增加乳腺样结构的形成。成纤维细胞促进iPSC衍生的MLO在体外和体内条件下产生乳腺样结构。我们的研究结果为利用iPSCs进行乳房重建奠定了基础。在线版本包含补充材料，可通过10.1186/s13287-022-03023-7获得。
Breast cancer is the most common malignancy in women worldwide, and its treatment largely depends on mastectomy. Patients after mastectomy suffer from crippled body image, self-esteem, and quality of life. Post-mastectomy breast reconstruction can improve patients’ psychosocial health. Although silicone and fat have been widely used for breast reconstruction, they have remarkable limitations. Our study aimed to establish an improved method for breast reconstruction from human-induced pluripotent stem cells (iPSCs). We used a two-step procedure to induce mammary-like organoids (MLOs) from iPSCs and applied transcriptome sequencing to analyze the gene expression profiles during the development process from embryoid bodies (mEBs) to MLOs. Moreover, we evaluated the in vitro effect of fibroblasts cell line HFF (human foreskin fibroblasts) on the size and morphology of MLOs and explored the in vivo effect of HFF on regeneration rate of MLOs. MLOs had a similar gene expression profile and morphogenesis as the normal mammary glands. Furthermore, the addition of HFF increases the branching ratio and organoid diameters and facilitates the formation of multiple cell layers duct-like structures in MLOs in vitro. Finally, orthotopical transplantation of the MLOs to cleared mammary gland fad pad of NSG mice showed that HFF increases the formation of mammary gland-like structures. Fibroblasts facilitate iPSC-derived MLOs to generate mammary gland-like structures in both in vitro and in vivo conditions. Our findings lay a foundation for breast reconstruction by using iPSCs. The online version contains supplementary material available at 10.1186/s13287-022-03023-7.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
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作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
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影响因子：
7.2
作者：
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通讯作者：
Streuli, Charles H.
影响因子：
9
作者：
Momoh, Adeyiza O.;Cohen, Wess A.;Matros, Evan
通讯作者：
Matros, Evan