Trophic and immunomodulatory effects of adipose tissue derived stem cells in a preclinical murine model of endometriosis

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.

Interferon Signaling in the Endometrium and in Endometriosis

“…The transfer of MSCs derived from normal adipose tissue leads to decreases in the size of ectopic endometrial lesions in rats with endometriosis due to the downregulation of proinflammatory cytokines, including IFN and TNFα, in peritoneal macrophages and ectopic endometrial lesions that are required for endometriosis progression [ 96 ]. In the murine model of endometriosis, intravenous administrated adipose tissue-derived MSC (Ad-MSC) directly migrates to endometriosis lesions and inhibits the growth of endometriosis lesions, by suppressing the expressions of proinflammatory cytokines, including monocyte chemotactic protein-1 ( MCP1 ), interleukin-6 ( IL6 ), and leukemia inhibitory factor ( LIF ) and pro-fibrotic cytokine such as tumor growth factor-β1 ( IGFB1 ) [ 97 ]. However, the efficacy of MSC therapy for endometriosis is still controversial.…”

Transwell Culture with Adipose Tissue-Derived Stem Cells and Fertilized Eggs Mimics the In Vivo Development of Fertilized Eggs to Blastocysts in the Fallopian Tube: An Animal Study

“…ASC isolation was conducted in accordance with a previously documented protocol [ 36 ]. In brief, subcutaneous adipose tissue specimens were obtained from ICR mice to procure adipose-derived regenerative cells (ADRCs).…”

“…Flow cytometric analyses of ASCs were performed according to a previously reported protocol [ 36 ]. In brief, ASCs were suspended in a staining buffer (R&D Systems, Minneapolis, MN, USA).…”

Impact of administering umbilical cord‐derived mesenchymal stem cells to cynomolgus monkeys with endometriosis

“…Umbilical cord (UC)‐derived MSCs (UC‐MSCs) inhibit endometriotic cell proliferation in vitro 5,6 . In rodent models, adipose tissue‐derived stem cells inhibited the growth of endometriosis‐like lesions 7,8 . In contrast, Abomaray et al demonstrated that MSCs derived from ectopic and eutopic endometrial tissues are pluripotent and support the growth of endometriotic lesions through immunosuppressive effects 9 .…”

“…5,6 In rodent models, adipose tissue-derived stem cells inhibited the growth of endometriosis-like lesions. 7,8 In contrast, Abomaray et al demonstrated that MSCs derived from ectopic and eutopic endometrial tissues are pluripotent and support the growth of endometriotic lesions through immunosuppressive effects. 9 The same authors also concluded that the use of adipose tissue-derived MSCs should not be considered a potential therapy for endometriosis.…”