Published online May 26, 2020. doi: 10.4252/wjsc.v12.i5.368
Peer-review started: February 24, 2020
First decision: March 28, 2020
Revised: April 3, 2020
Accepted: April 23, 2020
Article in press: April 23, 2020
Published online: May 26, 2020
Intrauterine adhesion (IUA) can cause serious damage to women's reproductive health. In our previous studies, we demonstrated that menstrual-derived stromal stem cells (MenSCs), with high proliferative capacity and self-renewal ability, have a powerful therapeutic effect in patients with severe IUA.
Safety assessment of MenSCs transplantation is essential for its further application in patients with severe IUA.
The purpose of this study was to evaluate the short-, medium-, and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA, with a focus on toxicity and tumorigenicity.
MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model, for 3 d, 3 mo, and 6 mo separately, to monitor the corresponding acute, sub-chronic, and chronic effects. Healthy rats of the same age served as negative controls. Toxicity effects were evaluated by body weight, organ weight, histopathology, hematology, and biochemistry tests. Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.
Compared with the same week-old control group, all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight, main organ weight, or blood cell composition during the acute, sub-chronic, and chronic observation periods. At the same time, serum biochemical tests showed no adverse effects on metabolism or liver and kidney function. After 4 wk of subcutaneous injection of MenSCs in Balb/c-nu nude mice, no tumor formation or cell metastasis was observed. Moreover, there was no tumor colony formation of MenSCs during soft agar culture in vitro.
There was no acute, sub-chronic, or chronic poisoning, infection, tumorigenesis, or endometriosis in rats with intrauterine adhesions after MenSC transplantation. The above results suggested that intrauterine transplantation of MenSCs is safe for endometrial treatment.
MenSCs are not only safe but also a promise source of cells for treating IUA and other types of endometrial damage. In addition, it is necessary to conduct longer follow-up studies on patients to fully ensure the safety of MenSC application.