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Although haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) has achieved similar survival to HLA-identical sibling donor (ISD) transplantation, the delayed hematopoietic engraftment as well as higher incidence of graft-versus-host-disease (GVHD), results in prolonged hospitalization, higher costs, and increased morbidity. In this study, a prospective, non-randomized clinical study was designed to evaluate the outcomes of patients who underwent HID HSCT supported by cord blood or ISD HSCT. Between May 2017 and November 2020, 113 patients were enrolled to undergo HID HSCT supported by cord blood (n=88) or ISD HSCT (n=25). The cumulative incidence of neutrophil and platelet engraftment at 30days was comparable in these two groups. Importantly, there was no significant difference in the cumulative incidence of grade II-IV aGVHD at 100days (20.5% [95% confidence interval [CI]: 12.2%–28.8%] versus 12.0% [95% CI: 0.2%–23.8%], P = 0.32) and cGVHD at 1 year (19.5% [95% CI: 11.2%–27.8%] versus 16.6% [[95% CI: 1.3%–31.9%] P = 0.70) between the two groups. Among the HID and ISD groups, the 2-year disease free survival was 76.8 and 80.0% (P = 0.83), the 2-year overall survival was 82.4 and 88.0% (P = 0.66), the 2-year GVHD-free, relapse-free survival was 68.9 and 75.3% (P = 0.62), respectively. Our results indicate that HID transplantation supported by cord blood may offer a good alternative to ISD HSCT for patients with hematopoietic malignancies. Trial registration: Effect of co-infusion third party umbilical cord blood stem cells on haploidentical hematopoietic stem cell transplantation https://www.chictr.org.cn Reg. No. ChiCTR-OIN-17011426. [ABSTRACT FROM AUTHOR]

Previous study indicated that co-infusion of cord blood cells may potentially improve the outcome of haploidentical donor (HID) transplantation. In this study, we analyzed the outcomes of patients who underwent HID transplantation supported by cord blood when compared with HLA-matched unrelated donor (URD) transplantation. Starting in 2015, 40 patients with hematopoietic malignancies underwent HID transplantation and 26 patients underwent URD transplantation. Hematopoietic recovery, the incidences of grade II–IV acute graft-versus-host disease (GVHD) and chronic GVHD was comparable in the two groups. At two year, the relapse risk in HID group was significantly lower than in URD group (RR 4.630; 95%CI, 1.081–19.839; p =.039). Moreover, HID group have prolonged PFS (RR 2.642; 95%CI, 1.046–6.672; p =.040). In conclusion, HID transplantation supported by cord blood results in better outcomes compared with URD transplantation and it might be a favorable alternative to a HLA-matched URD transplantation. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) use multiple mechanisms to constrain both innate and adaptive immune responses to prevent graft-versus-host disease (GVHD). Myeloid-derived suppressor cells (MDSCs), as a heterogeneous population of early myeloid progenitor cells originating from bone marrow, are a naturally occurring immune regulatory population associated with inhibition of ongoing inflammatory responses, indicating their potential for GVHD therapy. There is accumulating evidence that MSCs and MDSCs do not act independently, but rather establish crosstalk. However, the role of MSCs in MDSC expansion and activation in GVHD remains unexplored. In vitro experiments included 2 groups: peripheral blood mononuclear cells (PBMCs) after mobilization and human umbilical cord blood-derived MSCs (UCB-MSCs) co-cultured with PBMCs. The number and functional difference of MDSCs in PBMCs were determined by flow cytometry. The culture supernatants of co-cultured cells were analyzed to identify cytokines involved in MDSC proliferation. The relationship between MSCs and MDSCs was clarified in GVHD and graft-versus-leukemia (GVL) animal models. In vitro experiments confirmed that UCB-MSCs secreted HLA-G protein to promote and maintain the proliferation of MDSCs in peripheral blood after granulocyte colony-stimulating factor mobilization, and UCB-MSCs mediated the function of MDSCs to inhibit the proliferation of T cells and promote the proliferation of regulatory T cells. UCB-MSCs overexpressing HLA-G induced MDSC production in recipient mice, improved the ability of MDSCs to suppress T cells and further reduced acute GVHD (aGVHD) symptoms and survival time without influencing GVL effects. UCB-MSCs expanded MDSCs via HLA-G/Ig-like transcript 4, reducing the severity of aGVHD without affecting GVL. The immunosuppressive potential of MSCs for the treatment of aGVHD significantly affects the development of MDSCs, thereby consolidating the position of MSCs in the prevention and treatment of aGVHD. [ABSTRACT FROM AUTHOR]

Several per- and polyfluoroalkyl substances (PFAS) have been phased out due to their adverse effects, and replaced by the short-chain perfluorobutanesulfonic acid (PFBS). However, the long-term impacts of PFBS on human health are unknown. We aimed to investigate the association between prenatal exposure to PFAS, especially PFBS and childhood adiposity at 5 years of age. We conducted a prospective birth cohort study involving 1,140 pregnant women from 2012 to 2017 in Shanghai. Fetal umbilical cord blood was collected at birth. A total of 404 children (196 girls) completed the adiposity measurements using a bioelectrical impedance analysis method and cord plasma PFAS measurements using LC-MS/MS. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between PFAS and childhood adiposity. The median concentration of PFAS in the cord plasma ranged from 0.05 (PFBS) to 6.74 ng/mL (PFOA). Results of multivariable linear regression found that in girls, PFBS had a significant positive association with waist circumference and waist to height ratio (P -values < 0.05). Girls in the highest tertile of PFBS concentrations had more fat mass, as well as higher body fat percentage, waist circumference, and waist to height ratio compared to those in the lowest tertile. However, girls in the second tertile of PFDoA had lower body fat percentage, waist circumference and fat mass. Adiposity at 5 years of age shows a positive association with prenatal exposure to PFBS in girls. These findings need to be further verified in larger prospective studies. • We conducted a birth cohort study in Shanghai. • Ten PFAS were measured in cord blood to assess prenatal exposure. • A total of 404 children completed both PFAS measurement and adiposity measurement using a bioelectrical impedance analysis method at 5 years old. • High exposure to PFBS may be of concern for childhood adiposity. [ABSTRACT FROM AUTHOR]