BACKGROUND:The therapeutic efficacy of moderate or severe intrauterine adhesions is poor.After synechotomy,the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age,which is an urgent problem to be solved in clinical practice.Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages,and they have received particular attention on the treatment of intrauterine adhesions.OBJECTIVE:To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.METHODS:Search terms were"mesenchymal stem cells,perinatal period,hydrogel,intrauterine adhesions,endometrial injury"in Chinese and English.Relative articles published from 2010 to 2024 were retrieved on PubMed,CNKI,and WanFang databases.As a result,80 articles that met the inclusion criteria were reviewed and analyzed.RESULTS AND CONCLUSION:(1)Similar to other sources of mesenchymal stem cells,perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions,and can meet the needs of autologous and allogeneic transplantation.(2)The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord,amniotic membrane,placenta,and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation,cellular immunity,paracrine,and promoting endometrial regeneration and angiogenesis,immune regulation,anti-endometrial cell apoptosis,inhibition of epithelial-mesenchymal transition,and anti-fibrosis.(3)Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions.On the basis of the effect of mesenchymal stem cells,the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells,promoting cell migration and adhesion,which is helpful to better promote endometrial regeneration and anti-fibrosis.It is beneficial to repair the damaged endometrial,improve endometrial receptivity and fertility,and reduce the recurrence rate.(4)A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions.Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels,and other effects and molecular mechanism of combined treatment of intrauterine adhesions.

BACKGROUND:The therapeutic efficacy of moderate or severe intrauterine adhesions is poor.After synechotomy,the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age,which is an urgent problem to be solved in clinical practice.Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages,and they have received particular attention on the treatment of intrauterine adhesions.OBJECTIVE:To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.METHODS:Search terms were"mesenchymal stem cells,perinatal period,hydrogel,intrauterine adhesions,endometrial injury"in Chinese and English.Relative articles published from 2010 to 2024 were retrieved on PubMed,CNKI,and WanFang databases.As a result,80 articles that met the inclusion criteria were reviewed and analyzed.RESULTS AND CONCLUSION:(1)Similar to other sources of mesenchymal stem cells,perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions,and can meet the needs of autologous and allogeneic transplantation.(2)The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord,amniotic membrane,placenta,and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation,cellular immunity,paracrine,and promoting endometrial regeneration and angiogenesis,immune regulation,anti-endometrial cell apoptosis,inhibition of epithelial-mesenchymal transition,and anti-fibrosis.(3)Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions.On the basis of the effect of mesenchymal stem cells,the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells,promoting cell migration and adhesion,which is helpful to better promote endometrial regeneration and anti-fibrosis.It is beneficial to repair the damaged endometrial,improve endometrial receptivity and fertility,and reduce the recurrence rate.(4)A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions.Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels,and other effects and molecular mechanism of combined treatment of intrauterine adhesions.

Objective:To investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency (POI).Methods:POI mouse was induced by treatment with zona pellucida 3 polypeptide fragment-Freund immune adjuvant. The animals were divided into normal group ( n=10), model group ( n=15) and hAMSCs group ( n=15). hAMSCs (1×10 6 cells/mouse) were transplanted by tail vein single injection. The oestrus cycles were evaluated by vaginal smears. The levels of follicle-stimulating hormone (FSH), estrogen and anti-Müllerian hormone (AMH) in serum were detected by enzyme-linked immunosorbent assay methods. Morphological changes of ovarian and uterus tissues were observed after HE staining. The expressions of homeobox A10 (HOXA10), tumor necrosis factor-α (TNF-α) and FSH receptor (FSHR) proteins in uterine were measured by immunohistochemistry. The endometrial receptivity was comprehensively assessed. Results:After hAMSCs transplanting 6 weeks, the rate of abnormal oestrus cycles in hAMSCs group [40.0% (6/15)] was lower than that in model group [86.7% (13/15), P=0.021]. Compared with the levels of serum FSH [(10.239±1.091) μg/L], estradiol [(103.325±4.952) ng/L] and AMH [(1.133±0.494) μg/L] in model group, the level of FSH in hAMSCs group [(7.664±0.735) μg/L] was significantly decreased ( P<0.001), the levels of estradiol [(126.883±23.370) ng/L] and AMH [(2.204±0.453) μg/L] were significantly increased in hAMSCs group ( P=0.015, P<0.001). Different from model group, the ovarian and uterine index were increased. A large number of healthy follicles at all stages were highly increased, but it was rare to find interstitial fibrosis and atresia follicles. The uterine wall and endometrium were thickened, and the number and volume of the glands were increased. The absorbance ( A) of HOXA10 in hAMSCs group (5.90±1.94) was higher than that in model group (2.79±1.27, P=0.029). The TNF-α A value of hAMSCs (3.83±1.23) group was significantly lower than that of model group (6.26±0.96, P=0.002). Although there was no significant difference on FSHR A value between hAMSCs group (3.61±1.66) and model group (2.74±0.22, P>0.05), the FSHR A value of model group was lower than that of normal group (4.13±0.54, P=0.006). Conclusion:hAMSCs transplantation could restore ovarian function of autoimmune POI mice meanwhile significantly improve uterine receptivity and fertility.

Objective:To investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency (POI).Methods:POI mouse was induced by treatment with zona pellucida 3 polypeptide fragment-Freund immune adjuvant. The animals were divided into normal group ( n=10), model group ( n=15) and hAMSCs group ( n=15). hAMSCs (1×10 6 cells/mouse) were transplanted by tail vein single injection. The oestrus cycles were evaluated by vaginal smears. The levels of follicle-stimulating hormone (FSH), estrogen and anti-Müllerian hormone (AMH) in serum were detected by enzyme-linked immunosorbent assay methods. Morphological changes of ovarian and uterus tissues were observed after HE staining. The expressions of homeobox A10 (HOXA10), tumor necrosis factor-α (TNF-α) and FSH receptor (FSHR) proteins in uterine were measured by immunohistochemistry. The endometrial receptivity was comprehensively assessed. Results:After hAMSCs transplanting 6 weeks, the rate of abnormal oestrus cycles in hAMSCs group [40.0% (6/15)] was lower than that in model group [86.7% (13/15), P=0.021]. Compared with the levels of serum FSH [(10.239±1.091) μg/L], estradiol [(103.325±4.952) ng/L] and AMH [(1.133±0.494) μg/L] in model group, the level of FSH in hAMSCs group [(7.664±0.735) μg/L] was significantly decreased ( P<0.001), the levels of estradiol [(126.883±23.370) ng/L] and AMH [(2.204±0.453) μg/L] were significantly increased in hAMSCs group ( P=0.015, P<0.001). Different from model group, the ovarian and uterine index were increased. A large number of healthy follicles at all stages were highly increased, but it was rare to find interstitial fibrosis and atresia follicles. The uterine wall and endometrium were thickened, and the number and volume of the glands were increased. The absorbance ( A) of HOXA10 in hAMSCs group (5.90±1.94) was higher than that in model group (2.79±1.27, P=0.029). The TNF-α A value of hAMSCs (3.83±1.23) group was significantly lower than that of model group (6.26±0.96, P=0.002). Although there was no significant difference on FSHR A value between hAMSCs group (3.61±1.66) and model group (2.74±0.22, P>0.05), the FSHR A value of model group was lower than that of normal group (4.13±0.54, P=0.006). Conclusion:hAMSCs transplantation could restore ovarian function of autoimmune POI mice meanwhile significantly improve uterine receptivity and fertility.

Cardiovascular Diseases ; Cardiovascular System ; Circadian Clocks/genetics* ; Circadian Rhythm ; Humans

OBJECTIVE: To investigate the evaluation value of preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) on the prognosis of patients with stage III colon cancer undergoing radical resection and postoperative adjuvant chemotherapy. METHODS: Electronic medical record were retrospectively retrived for stage III colon cancer patients who underwent radical surgery at Sun Yat-sen University Cancer Center from December 2007 to December 2013. Inclusion criteria were pathologically comfirmed colon adenocarcinoma, complete clinicopathological data, and postoperative XELOX (oxaliplatin + capecitabine) chemotherapy with follow-up of at least 3 months. Patients with neoadjuvant anti-tumor therapy, infectious disease, other malignant tumors and death of non-tumor causes within 3 months after operation were excluded. A total of 258 patients were included in this retrospective cohort study, including 146 males and 112 females with median age of 55 (22 to 85) years. Tumors of 100(38.8%) patients were located in the right hemicolon, and of 158 (61.2%) in the left hemicolon. Tumors of 194(75.2%) patients were highly and moderately differentiated, and of 64 (24.8%) were poorly differentiated. According to the TNM tumor pathological stage of AJCC 7th edition, 196 (76.0%) patients were stage IIIA to IIIB, and 62(24.0%) patients were stage IIIC. The median preoperative CEA was 3.8 (0.3 to 287.5) μg /L and the median cycle of the adjuvant chemotherapy was 6 (1 to 8). The cut-off value of preoperative LMR in prediction of 3-year overall survival (OS) outcome was determined by receiver operating characteristic (ROC) curve analysis. All patients were divided into low LMR group and high LMR group according to the critical value. Clinicopathological characteristics between the two groups were compared by using chi-square test or Fisher's exact test as appropriate. The 3-year disease-free survival and overall survival rate were estimated with the Kaplan-Meier method, and differences between two groups were assessed with the log-rank test. Univariate and multivariate analyses were performed through Cox regression model. RESULTS: ROC curve showed that the cut-off value of preoperative LMR in predicting 3-year overall survival was 4.29. Then 143 patients were divided into low LMR group (LMR<4.29) and 115 patients into high LMR group (LMR ≥ 4.29). Compared with high LMR group, the low LMR group presented higher proportions of male [62.2%(89/143) vs. 50.4%(58/115), χ²=4.167, P=0.041], right hemicolon cancer [44.8% (64/143) vs. 31.3% (36/115), χ²=4.858, P=0.028], and the largest tumor diameter>4 cm [60.1% (86/143) vs. 33.0% (38/115), χ²=18.748, P<0.001]. During a median follow-up of 46.0 (range, 3.0 to 74.0) months, 3-year disease-free survival rate was 83.8% in high LMR group and 78.9% in low LMR group, which was not significantly different (P=0.210). While 3-year overall survival rate in low LMR group was significant lower than that in high LMR group (86.6% vs. 97.2%, P=0.018). Univariate analysis revealed that preoperative low LMR (HR=2.841, 95%CI: 1.146 to 7.043, P=0.024), right hemicolon cancer (HR=2.865, 95%CI: 1.312 to 6.258, P=0.008) and postoperative adjuvant chemotherapy≥6 cycles (HR=0.420, 95%CI: 0.188 to 0.935, P=0.034) were the risk factors for poor overall survival. Multivariate analysis identified that preoperative low LMR (HR=2.550, 95%CI: 1.024 to 6.347, P=0.004) and right hemicolon cancer (HR=2.611, 95%CI: 1.191 to 5.723, P=0.017) were the independent risk factors for overall survival. CONCLUSIONS Preoperative peripheral blood LMR level represents an effective prognostic predictor for patients with stage III colon cancer receiving radical therapy. Low LMR indicates the poor prognosis and such patients require aggressive postoperative treatment strategy.
Adenocarcinoma ; blood ; drug therapy ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; blood ; drug therapy ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocyte Count ; methods ; Lymphocytes ; Male ; Middle Aged ; Monocytes ; Preoperative Care ; Prognosis ; Retrospective Studies ; Young Adult

Since the release rate of protein in hydrogels is directly dependent upon the size of the protein and the hydrogel, how to deliver low molecular weight protein for prolonged periods has always been a problem. In this article, we present a usage of self-assembling peptide (P3) with the RGD epitope on its N terminus. The concentration of the released insulin-like growth factor 1 (IGF-1) was determined by UV-vis spectroscopy and the release kinetics suggested a notable reduction of the IGF-1 release rate. Cell entrapment experiments revealed that IGF-1 delivery by biotinylated nanofibers could promote the proliferation of the mouse chondrogenic ATDC5 cells when compared with cells embedded within nanofibers with untethered IGF-1.
Animals ; Biotin ; Cell Line ; Delayed-Action Preparations ; Drug Carriers ; chemistry ; Hydrogels ; chemistry ; Insulin-Like Growth Factor I ; pharmacology ; Mice ; Nanofibers ; Oligopeptides ; chemistry

10.3969/j.issn.2095-4344.2013.23.010