uterine adhesion, also known as Asherman syndrome, is a common endometrial injury disease and has become the second leading cause of secondary infertility in women. Recently, a review published in "Stem Cell Research & Therapy" proposed that [1] and cell therapy can treat many diseases including thin endometrial and uterine adhesions; especially umbilical cord mesenchymal stem cell , which has the advantages of easy access, rapid self-renewal, and low immunogenicity. Innovative therapies based on the combination of stem cell and biomaterial are considered an ideal choice for regenerating endometrium.
Uterine cavity adhesion is caused by various factors to damage the intrauterine cavity and the basal endometrium of the cervical canal, and the adhesion between the uterine cavity myocardium and the cervical canal is formed. Due to the increase in invasive uterine cavity operations such as artificial abortion, the incidence of uterine cavity adhesions is also increasing. At present, treatment methods for uterine adhesions include surgically loosening the adhesion insulator, placing biological materials to prevent and treat readhesions, and using estrogen, aspirin, etc. to promote endometrial repair. However, these treatments are either incurable or have various side effects. Therefore, there is an urgent need to develop new treatment options.
stem cells, as a cell with multidirectional differentiation potential and secretion of multiple functional factors, are considered to be applicable to the treatment of infertility -related diseases. The mechanism of stem cells to treat infertility caused by uterine adhesions is mainly through the induction of cytokine and the production of growth factor to promote the repair and regeneration of inner membrane ; and through the immunomodulatory characteristics, the reduction of natural killer cell activity, the decrease of Th17 and Th1, and the increase of Treg cells and Th2.
pictures are from literature [1]
Case sharing: Stem cells treat uterine adhesions
In recent years, under the premise of certain results in theoretical research and preclinical trials, domestic and foreign researchers have successively carried out a number of clinical studies on stem cells for the treatment of uterine adhesions. The results show that stem cells treat infertility caused by uterine adhesions, and are expected to bring light to infertile patients [3-5]. Stem cells have been used in clinical studies to treat uterine adhesions for many years, and the accumulated successful cases are also increasing year by year.
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# 8 patients fulfilled their "child dream"
A prospective, non-controlled phase I clinical trial conducted by Gulou Hospital of Nanjing University [3] evaluated the safety and effectiveness of umbilical cord mesenchymal stem cells in the treatment of uterine adhesions. The relevant results were published in "Stem Cell Research & Therapy".
Research results show that umbilical cord mesenchymal stem cells may be a potential treatment for uterine adhesions. In this study, 26 patients with recurrent uterine adhesions caused infertility were included. 1×10^7 umbilical cord mesenchymal stem cells (UC-MSCs) were loaded onto the collagen scaffold, and transplanted into the patient's uterine cavity after the uterine adhesion was loosened. Then, 3 months of follow-up was conducted to evaluate the changes in the patients' endometrial thickness, uterine adhesion score and endometrial proliferation and differentiation-related molecules.
pictures are from literature [3]
follow-up results found that [3], no serious adverse events related to treatment occurred after UC-MSCs transplantation; 3 months after surgery, the average endometrial thickness of the patients increased significantly compared with before treatment, and the uterine adhesion score was lower than before. In addition, histology studies have shown that the proliferation, differentiation and neovascularization of the endometrium after treatment have improved. By the end of the 30-month follow-up period, 10 of the 26 patients were pregnant, and 8 had given birth without obvious birth defects and placental complications.
Figure shows ultrasound comparison before and after treatment. Pictures are from literature [3]
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#7 patients had obvious recovery of the endometrium and were successfully conceived
A study conducted by Shengjing Hospital of China Medical University in China [4] used autologous menstrual blood mesenchymal stem cells (MB-MSC) to treat 7 patients with severe Asherman syndrome. They all had no effect on traditional treatment methods.After enrollment, they received MB-MSC transplantation and then hormone therapy. After stem cell transplantation, the endometrial thickness of 5 patients increased significantly, reaching 7 mm, 1 patient became pregnant naturally, and 2 were conceived through assisted reproductive technology.
Pictures from literature [4]
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#5 patients recovered from menstrual cycle
Another study [5] patients with refractory uterine adhesions failed to receive standard treatment and received single nucleated cell cells (MNCs) transplantation, implanted sub-endometrium, and oral exogenous estrogen therapy. They were tested for endometrial thickness after 3, 6 and 9 months of treatment, respectively. The results showed that after was treated with cell transplantation, the endometrial thickness of 6 patients was significantly higher than before treatment, and 5 of them resumed their menstrual cycles and the endometrial regeneration was good. This study once again shows that autologous cell transplantation is a very promising treatment for uterine adhesions.
Pictures from literature [5]
Domestic innovative therapies for uterine cavity adhesions recruitment
Uterine cavity adhesions have caused many couples to suffer from infertility and cannot conceive the next generation normally. Its traditional treatment methods have limited efficacy. In recent years, scientific research has confirmed that stem cell-based regenerative medical methods can effectively repair the endometrium of patients with uterine adhesions and improve fertility.
At present, multiple domestic research teams are carrying out innovative therapies for uterine adhesions, in order to provide a new, safe and effective treatment plan for the clinical treatment of refractory uterine adhesions.
At the same time, there are also a number of registration projects related to stem cells in the treatment of endometrial injury or uterine adhesions in China. The clinical development of
stem cells has brought a breakthrough in the treatment of uterine adhesions and has successfully helped some infertile patients realize their desire to give birth. At present, a large amount of research is underway at home and abroad. Boya is providing stem cell technical support for clinical treatment of uterine adhesions. I believe that in the future, stem cells will make greater progress in the treatment of uterine adhesions.
Written by: Fujian Medical University YANG
Expert review: Jiangsu University Affiliated Hospital Professor Li Jing
References:
[1] Gharibeh N, Aghebati-Maleki L, Madani J, Pourakbari R, Yousefi M, Ahmadian Heris J. Cell-based therapy in thin endometrium and Asherman syndrome. Stem Cell Res Ther. 2022;13(1):33. Published 2022 Jan 28.
https://pubmed.ncbi.nlm.nih.gov/35090547/
[2] Chen Fang, Sui Long. Research progress of stem cells in uterine adhesion treatment [J]. International Journal of Obstetrics and Gynecology, 2014, 41(06):632-635.
https://kns.cnki.net/kcms/detail/detail.aspx?dbcode=CJFD&dbname=CJ FDLAST2015&filename=GWVC201406019&uniplatform=NZKPT&v=wCoHWLYEMXQk3pUEWubmEfB_03B8w5g7Q9fKQdekbY-cXdSYAcD69eGcs4K2EOqG
[3] Cao Y, Sun H, Zhu H, Zhu X, Tang X, Yan G, Wang J, Bai D, Wang J, Wang L, Zhou Q, Wang H, Dai C, Ding L, Xu B, Zhou Y, Hao J, Dai J, Hu Y. Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uteterine adhesion: a phase I clinical trial. Stem Cell Res Ther. 2018 Jul 11;9(1):192.
https://pubmed.ncbi.nlm.nih.gov/29996892/
[4] Tan J, Li P, Wang Q, Li Y, Li X, Zhao D, Xu X, Kong L. Autologous menstrual blood-derived stromal cells translation for severe Asherman's syndrome. Hum Reprod. 2016 Dec;31(12):2723-2729.
https://pubmed.ncbi.nlm.nih.gov/27664218/
[5] Singh N, Mohanty S, Seth T, Shankar M, Bhaskaran S, Dharmendra S. Autologous stem cell transplantation in refractory Asherman's syndrome: A novel cell based therapy. J Hum Reprod Sci. 2014 Apr;7(2):93-8.
https://pubmed.ncbi.nlm.nih.gov/25191021/
