Development of tailor-made cell therapy for implantation failure

在这项研究中，我们试图开发一种新的量身定制的细胞治疗由于各种子宫内膜功能障碍的种植失败。本研究首先建立了小鼠子宫内膜细胞的分离培养方法。这些子宫内膜细胞能够在适当的条件下终末分化，并且在相应的腺病毒感染后还能够高度表达报告标记蛋白，例如绿色荧光蛋白和β-半乳糖苷酶（β-Gal）。然后，我们将这些基因修饰的子宫内膜细胞移植到小鼠子宫中，以检查它们在移植部位的存活率。移植后1周，移植子宫内仍有β-Gal表达细胞，提示我们的策略和方法可用于子宫内膜功能障碍等子宫疾病的细胞治疗。为了验证我们可能的细胞疗法的有效性，应该建立表现出子宫功能障碍的小鼠模型，特别是子宫内膜。为此，我们开发了一种使用超声和微泡的女性生殖道基因转移的新方法，这使我们能够在理论上随时上调和/或下调子宫内膜基因。进一步的研究组合使用我们的上述方法和系统将证实我们的策略，其中定制的细胞疗法可以应用于治疗由于子宫内膜功能障碍引起的着床失败。

In this study, we have attempted to develop a novel tailor-made cell therapy for implantation failure due to various endometrial dysfunctions. We first established the isolation and culture procedures of endometrial cells from the mouse uterus. These endometrial cells were capable to terminally differentiate under the appropriate condition and also to highly express reporter marker proteins such as green fluorescent protein and β-galactosidase (β-Gal) upon infection of the corresponding adenovirus. We then transplanted these genetically-modified endometrial cells into the mouse uterus to examine their survival rates at the transplanted sites. β-Gal-expressing cells were found in the transplanted uterus even one week after transplantation, suggesting that our strategy and methods can be applied as a possible cell therapy for the uterine diseases such as endometrial dysfunction. To validate the effectiveness of our possible cell therapy, a mouse model exhibiting dysfunction of the uterus, in particular, the enodmetrium, should be established. For this purpose, we have developed a novel method of female reproductive tract gene transfer using ultrasound and micro-bubbles, which enables us to up- and/or down-regulate endometrial genes theoretically at any time. Further studies combinatorially using our above-mentioned methods and systems will substantiate our strategy in which a tailor-made cell therapy can be applied to treat implantation failure due to endometrial dysfunction.