image: The uterus comprises the endometrium, myometrium, and perimetrium, among other layers. Damage or infection to the endometrium can result in regenerative disorders such as IUA and TE. Both IUA and TE exhibit a shared characteristic: endometrial fibrosis, which can be visualized through Masson’s trichrome staining (blue: collagen fibers; red: muscle). Existing treatments for endometrial fibrosis primarily encompass hysteroscopic adhesiolysis, barrier methods for adhesion prevention, and high-dose estrogen therapy; however, their effectiveness remains limited.
Credit: ©Science China Press
In a recent review published in Science China Life Sciences, researchers from Nanjing Drum Tower Hospital and the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, have shed light on the promising advancements in regenerative medicine for addressing fibrotic endometrial disorders such as intrauterine adhesion (IUA) and thin endometrium (TE). These conditions, characterized by scar formation and reduced endometrial thickness, respectively, pose significant challenges in human reproduction.
IUA, also known as Asherman's syndrome, occurs when the uterine cavity becomes partially or completely obliterated by fibrous tissue, often due to uterine surgeries or infections. TE, on the other hand, is defined by an endometrial thickness below 7mm, frequently associated with previous uterine manipulations. Both conditions impair the uterus's ability to accept embryo implantation, leading to infertility and other reproductive complications.
The conventional treatments for IUA and TE, including hysteroscopic adhesiolysis, estrogen therapies, and barrier methods, have shown limited success, particularly in severe cases. This has prompted the exploration of innovative regenerative therapies that aim to restore the endometrial function and structure.
The review highlights the therapeutic potential of stem cells, particularly mesenchymal stem cells (MSCs) derived from sources such as bone marrow, adipose tissue, and umbilical cord Wharton's jelly. MSCs possess self-renewal and differentiation capabilities, making them ideal candidates for tissue regeneration. Preclinical and clinical studies have demonstrated that transplanting MSCs into the endometrial compartment can reduce fibrosis, stimulate angiogenesis, and improve pregnancy outcomes.
In addition to stem cells, biomaterials play a crucial supportive role in endometrial regeneration. Collagen scaffolds, for instance, have been shown to provide a conducive microenvironment for stem cell survival, proliferation, and differentiation. By using collagen scaffolds as carriers for MSC transplantation, researchers have been able to achieve long-term endometrial regeneration and functional restoration.
One notable clinical trial reported in the review involved the transplantation of autologous bone marrow stem cells combined with collagen scaffolds in women with severe IUA. The results showed a significantly higher ongoing pregnancy rate in the treatment group compared to the control group. Similarly, trials using umbilical cord-derived MSCs on collagen scaffolds have also demonstrated promising outcomes in both IUA and TE patients.
The review further discusses the importance of understanding the molecular mechanisms underlying IUA and TE in developing effective therapeutic strategies. Advances in single-cell sequencing and other high-throughput technologies have provided insights into the complex interplay between immune cells, stromal cells, and epithelial cells in the endometrial microenvironment.
In conclusion, the review underscores the promise of regenerative medicine in treating fibrotic endometrial disorders. With continued research and optimization of stem cell sources, biomaterials, and delivery methods, the prospect of successful endometrial regeneration and fertility restoration becomes increasingly promising.
About Nanjing Drum Tower Hospital
Nanjing Drum Tower Hospital, affiliated with Nanjing University Medical School, is a leading healthcare institution in China known for its excellence in clinical care, teaching, and research. The hospital's Department of Obstetrics and Gynecology is at the forefront of research and treatment in reproductive medicine, including innovative therapies for infertility and gynecological disorders.
Journal
Science China Life Sciences
Method of Research
Systematic review