Abstract
BackgroundThe 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).MethodsAutologous 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.ResultsFluorescence-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.ConclusionsAutologous 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.
Highlights
The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGelTM3D transplantation to activate the Bone morphogenetic protein 7 (BMP7)-Smad5 signaling pathway to treat intrauterine adhesions (IUA)
Autologous ADSCs can be used in combination with ShakeGelTM3D to maintain functionality and create a viable three-dimensional growth environment
We evaluated the therapeutic effects of a complex of mouse autologous ADSCs loaded on ShakeGelTM3D in an IUA mouse model by activating the BMP7-Smad5 signaling pathway, which increased local perseverance and stem cells activity
Summary
The objective was to explore the therapeutic effect of autologous adipose-derived stem cells (ADSCs) combined with ShakeGelTM3D transplantation to activate the BMP7-Smad signaling pathway to treat intrauterine adhesions (IUA). Intrauterine adhesions (IUA), the most common cause of uterine infertility, partially or completely block the uterine cavity and/or cervical canal and are caused by endometrial basal layer injury. There are several hypotheses about the pathogenesis of IUA, including the fibrosis hyperplasia theory, the neural reflex theory, abnormal differentiation of stem cells, changes in the uterine microenvironment and fibrosis, abnormal regulation of signaling pathways, and inflammatory response caused by adherent fibroblasts. Some shortcomings and deficiencies of these antiadhesion strategies, such as resistance to secondary surgery, limited isolation area, induction of intrauterine inflammatory response, and difficulty in endometrial regeneration, have forced researchers to continue to explore new treatment options
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