The restorative effects of adipose derived mesenchymal stem cells (A-MSCs) on damaged ovaries

ObjectiveThe aim of present study is to address whether A-MSCs are capable to restore ovarian function by their local transplantation into anti-cancer drug administrated damaged ovaries.DesignExperimental study using animal models.Materials and MethodsCyclophosphamide (CTX) was administrated intraperitoneally into rats (Wistar-Imamichi, 8 weeks old) at 50mg/kg followed by 8mg/kg for 13 consecutive days to induce ovarian failure. Then, 2x106 cells of A-MSCs or tail fibroblast (TF) cells were transplanted into left side of ovaries (right side: non-injected control). Rats were euthanized 8 weeks after transplantation and cell or sham (saline) transplanted ovaries were sectioned to count the follicle number and immunostained with CD34 antibody. Quantitative (q)RT-PCR was performed to quantify VEGF and StAR mRNA expression in ovaries.ResultsThe mean total number of total follicles and corpus lutea were significantly decreased in CTX treated ovaries (25.5±1.8 vs 34.4±2.4; control), therefore ovarian failure was successfully induced. The number of CD34 positive cells per 1mm2 of corpus lutea in A-MSC transplanted ovaries was increased significantly (319±43.0 vs 171.8±31.7; saline and 178.8±47.0; TF). The ratio of total follicle number in A-MSC transplanted ovaries to non transplanted ovaries was relatively higher in A-MSC transplanted ovaries (1.30±0.10 vs 1.03±0.10; saline and 0.96±1.8; TF). The ratio of mRNA expression of VEGF (V) and StAR (S) in cell transplanted ovaries to non transplanted ovaries was significantly higher in A-MSC transplanted ovaries (1.86±0.01 (V), 2.89±0.27 (S) vs 1.01±0.02 (V), 1.05±0.07 (S); saline and 0.86±0.05 (V), 0.88±0.03 (S); TF).ConclusionOur results showed that A-MSC transplantation into ovaries promoted angiogenesis and restored ovarian function. Our finding suggests the future therapeutic potential for patients with ovarian failure to improve their ovarian function by A-MSC transplantation. ObjectiveThe aim of present study is to address whether A-MSCs are capable to restore ovarian function by their local transplantation into anti-cancer drug administrated damaged ovaries. The aim of present study is to address whether A-MSCs are capable to restore ovarian function by their local transplantation into anti-cancer drug administrated damaged ovaries. DesignExperimental study using animal models. Experimental study using animal models. Materials and MethodsCyclophosphamide (CTX) was administrated intraperitoneally into rats (Wistar-Imamichi, 8 weeks old) at 50mg/kg followed by 8mg/kg for 13 consecutive days to induce ovarian failure. Then, 2x106 cells of A-MSCs or tail fibroblast (TF) cells were transplanted into left side of ovaries (right side: non-injected control). Rats were euthanized 8 weeks after transplantation and cell or sham (saline) transplanted ovaries were sectioned to count the follicle number and immunostained with CD34 antibody. Quantitative (q)RT-PCR was performed to quantify VEGF and StAR mRNA expression in ovaries. Cyclophosphamide (CTX) was administrated intraperitoneally into rats (Wistar-Imamichi, 8 weeks old) at 50mg/kg followed by 8mg/kg for 13 consecutive days to induce ovarian failure. Then, 2x106 cells of A-MSCs or tail fibroblast (TF) cells were transplanted into left side of ovaries (right side: non-injected control). Rats were euthanized 8 weeks after transplantation and cell or sham (saline) transplanted ovaries were sectioned to count the follicle number and immunostained with CD34 antibody. Quantitative (q)RT-PCR was performed to quantify VEGF and StAR mRNA expression in ovaries. ResultsThe mean total number of total follicles and corpus lutea were significantly decreased in CTX treated ovaries (25.5±1.8 vs 34.4±2.4; control), therefore ovarian failure was successfully induced. The number of CD34 positive cells per 1mm2 of corpus lutea in A-MSC transplanted ovaries was increased significantly (319±43.0 vs 171.8±31.7; saline and 178.8±47.0; TF). The ratio of total follicle number in A-MSC transplanted ovaries to non transplanted ovaries was relatively higher in A-MSC transplanted ovaries (1.30±0.10 vs 1.03±0.10; saline and 0.96±1.8; TF). The ratio of mRNA expression of VEGF (V) and StAR (S) in cell transplanted ovaries to non transplanted ovaries was significantly higher in A-MSC transplanted ovaries (1.86±0.01 (V), 2.89±0.27 (S) vs 1.01±0.02 (V), 1.05±0.07 (S); saline and 0.86±0.05 (V), 0.88±0.03 (S); TF). The mean total number of total follicles and corpus lutea were significantly decreased in CTX treated ovaries (25.5±1.8 vs 34.4±2.4; control), therefore ovarian failure was successfully induced. The number of CD34 positive cells per 1mm2 of corpus lutea in A-MSC transplanted ovaries was increased significantly (319±43.0 vs 171.8±31.7; saline and 178.8±47.0; TF). The ratio of total follicle number in A-MSC transplanted ovaries to non transplanted ovaries was relatively higher in A-MSC transplanted ovaries (1.30±0.10 vs 1.03±0.10; saline and 0.96±1.8; TF). The ratio of mRNA expression of VEGF (V) and StAR (S) in cell transplanted ovaries to non transplanted ovaries was significantly higher in A-MSC transplanted ovaries (1.86±0.01 (V), 2.89±0.27 (S) vs 1.01±0.02 (V), 1.05±0.07 (S); saline and 0.86±0.05 (V), 0.88±0.03 (S); TF). ConclusionOur results showed that A-MSC transplantation into ovaries promoted angiogenesis and restored ovarian function. Our finding suggests the future therapeutic potential for patients with ovarian failure to improve their ovarian function by A-MSC transplantation. Our results showed that A-MSC transplantation into ovaries promoted angiogenesis and restored ovarian function. Our finding suggests the future therapeutic potential for patients with ovarian failure to improve their ovarian function by A-MSC transplantation.