Yun-Xia Zhao1, Shao-Rong Chen1, Qiao-Yi Huang1, Wei-Can Chen2, Tian Xia3, Yan-Chuan Shi4,5, Hong-Zhi Gao6, Qi-Yang Shi7, Shu Lin8,9. 1. Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China. 2. Department of Anaesthesiology, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, China. 3. School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, Fujian province, China. 4. Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. 5. Faculty of Medicine, St Vincent's Clinical School, Univeristy of New South Wales, Sydeny, New South Wales, 2052, Australia. 6. Clinical Center for Molecular Diagnosis and Therapy, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China. 7. Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China. wsqy214@163.com. 8. Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. shulin1956@126.com. 9. Centre of Neurological and Metabolic Research, the Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China. shulin1956@126.com.
Abstract
BACKGROUND: The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGel™3D transplantation to activate the BMP7-Smad5 signaling pathway to treat intrauterine adhesions (IUA). METHODS: Autologous ADSCs were isolated and then merged with ShakeGel™3D. The IUA model was established by mechanical injury. The third generation of autologous ADSCs was injected directly into the uterus in combination with ShakeGel™3D. After 7 days of treatment, endometrial morphology, number of endometrial glands, endometrial fibrosis area, and fibrosis biomarker analysis by RT-PCR and IHC were examined. BMP7 and phosphorylation of Smad5 were also detected, and the recovery of infertility function in treated mice was evaluated. RESULTS: Fluorescence-activated cell sorting (FACS) showed that autologous ADSCs expressed CD105 (99.1%), CD29 (99.6%), and CD73 (98.9%). Autologous ADSCs could still maintain a good growth state in ShakeGel™3D. Histological examination revealed that the number of endometrial glands increased significantly, and the area of fibrosis decreased. At the same time, the expression of BMP7 and Smad5 in the ADSCs + Gel group was significantly upregulated, and the final reproductive function of this group was partly recovered. CONCLUSIONS: Autologous ADSCs can be used in combination with ShakeGel™3D to maintain functionality and create a viable three-dimensional growth environment. The combined transplantation of autologous ADSCs and ShakeGel™3D promotes the recovery of damaged endometrial tissue by increasing BMP7-Smad5 signal transduction, resulting in endometrium thickening, increased number of glands, and decreased fibrosis, leading to restoration of partial fertility.
BACKGROUND: The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGel™3D transplantation to activate the BMP7-Smad5 signaling pathway to treat intrauterine adhesions (IUA). METHODS: Autologous ADSCs were isolated and then merged with ShakeGel™3D. The IUA model was established by mechanical injury. The third generation of autologous ADSCs was injected directly into the uterus in combination with ShakeGel™3D. After 7 days of treatment, endometrial morphology, number of endometrial glands, endometrial fibrosis area, and fibrosis biomarker analysis by RT-PCR and IHC were examined. BMP7 and phosphorylation of Smad5 were also detected, and the recovery of infertility function in treated mice was evaluated. RESULTS: Fluorescence-activated cell sorting (FACS) showed that autologous ADSCs expressed CD105 (99.1%), CD29 (99.6%), and CD73 (98.9%). Autologous ADSCs could still maintain a good growth state in ShakeGel™3D. Histological examination revealed that the number of endometrial glands increased significantly, and the area of fibrosis decreased. At the same time, the expression of BMP7 and Smad5 in the ADSCs + Gel group was significantly upregulated, and the final reproductive function of this group was partly recovered. CONCLUSIONS: Autologous ADSCs can be used in combination with ShakeGel™3D to maintain functionality and create a viable three-dimensional growth environment. The combined transplantation of autologous ADSCs and ShakeGel™3D promotes the recovery of damaged endometrial tissue by increasing BMP7-Smad5 signal transduction, resulting in endometrium thickening, increased number of glands, and decreased fibrosis, leading to restoration of partial fertility.