Development of tailor-made cell therapy for implantation failure

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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.