Trophic and immunomodulatory effects of adipose tissue derived stem cells in a preclinical murine model of endometriosis
Toyofumi Hirakawa, Fusanori Yotsumoto, Naoto Shirasu, Chihiro Kiyoshima, Daichi Urushiyama, Kenichi Yoshikawa, Kohei Miyata, Masamitsu Kurakazu, Kaori Koga, Mikiko Aoki, Kazuki Nabeshima, Kaori Koga, Yutaka Osuga, Hiroaki Komatsu, Fuminori Taniguchi, Tasuku Harada, Shin’ichiro Yasunaga, Shingo Miyamoto
Abstract
Endometriosis, which exhibits enigmatic pathological features such as stromal fibrosis and proliferation of ectopic epithelial cells, is known as a refractory disease. Mesenchymal stem cells modulate the fibrosis in stromal tissues through their trophic and immunomodulatory properties. To investigate the potential of stem cells in treating endometriosis, we examined the secondary morphology and molecular alterations in endometriosis-like lesions after the administration of adipose tissue-derived stem cells (ASCs) to an experimental murine model of endometriosis. The infused ASCs were found integrated in the endometriosis-like lesions. Accompanied by the suppression of stromal fibrosis and proliferation of endometriotic epithelial cells, the infusion of ASCs with stemness potential (early passage of ASCs) suppressed the growth of endometriosis-like lesions and inhibited the expression of pro-inflammatory and pro-fibrotic cytokines, whereas no significant attenuation of endometriosis-like lesions occurred after the infusion of ASCs without stemness potential (late passage of ASCs). Accordingly, the trophic and immunomodulatory properties of ASCs may regulate fibrosis in endometriosis-like lesions, suggesting that regenerative medicine could be recognized as an innovative treatment for patients with endometriosis through the accumulation of evidence of preclinical efficacy.