Engraftment of self-renewing endometrial epithelial organoids promotes endometrial regeneration by differentiating into functional glands in rats

植入自我更新的子宫内膜上皮类器官可通过分化为大鼠功能性腺体促进子宫内膜再生

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作者:Yana Ma, Jingjing Qian, Xin Xu, Cheng Wei, Minyuan Wang, Peipei Zhang, Sijia Chen, Lingyan Zhang, Yanling Zhang, Yanpeng Wang, Wenzhi Xu, Mengying Liu #, Xiaona Lin #

Discussion

EEOs offer a transformative approach to address the challenges of endometrial trauma. Their remarkable regenerative potential holds promise for the restoration of damaged endometrium. As we venture into the future, the concept of utilizing patient-specific EEOs for transplantation emerges as a tantalizing prospect. However, the EEOs in our experiments were mainly cultured in Matrigel, which has barriers to clinical translation as a biomaterial, a new biomaterial to be explored. Secondly, our experiments have been successful only in rat models, and more efforts need to be made before clinical translation.

Methods

We developed rat EEOs (rEEOs) mimicking the features of the rat endometrium. Subsequently, we created a rat model of endometrial injury to compare the effects of rEEOs and rat BMSCs (rBMSCs) on endometrial regeneration and reproductive recovery. Bulk RNA-sequencing analysis was conducted to further investigate the capacity of rEEOs for endometrial regeneration and to identify discrepancies between rEEOs and rBMSCs. Additionally, to track the fate of the transplanted cells in vivo, we transplanted green fluorescent protein (GFP) -labelled rEEOs or red fluorescent protein (RFP) -labelled rBMSCs.

Results

In a rat model of endometrial injury, we observed that fertility recovery in rats transplanted with rEEOs was more comparable to that of normal rats than in those treated with rBMSC. rEEOs possess a high concentration of endometrial epithelial stem/progenitor cells and secrete vascular endothelial growth factor (VEGF)-A to promote endometrial neovascularization. Significantly, we observed that cells from GFP-labelled rEEOs could integrate and differentiate into functional glands within the injured endometrium of recipient rats.

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