Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies.Umbilical cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders.This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP.The research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion phase.Adverse events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period.Ultimately,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,respectively.Thirteen patients(13/18,72.2%)experienced one or more treatment emergent adverse events.Serious adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion phase.The overall response rate was 44.4%(8/18)among all enrolled patients.To sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(ClinicalTrials.gov ID:NCT04014166).

Applicability of cosmic-ray neutron sensor for measuring soil moisture at the agricultural-pastoral ecotone in northwest China

Accurate monitoring of soil moisture is crucial in hydrological and ecological studies.Cosmic-ray neutron sensors(CRNS)measure area-average soil moisture at field scale,filling a spatial scale gap between in-situ observations and remote sensing measurements.However,its applicability has not been assessed in the agricultural-pastoral ecotone,a data scarce semiarid and arid region in Northwest China(APENC).In this study,we calibrated and assessed the CRNS(the standard N0 method)estimates of soil moisture.Results show that Pearson correlation coefficient,RP,and the root mean square error(RMSE)between the CRNS soil moisture and the gravimetric soil moisture are 0.904 and less than 0.016 m3 m–3,respectively,indicating that the CRNS is able to estimate the area-average soil moisture well at our study site.Compared with the in-situ sensor network measurements(ECH2O sensors),the CRNS is more sensitive to the changes in moisture in its footprint,which overestimates and underestimates the soil moisture under precipitation and dry conditions,respectively.The three shape parameters a0,a1,a2 in the standard calibration equation(N0 method)are not well suited to the study area.The calibrated parameters improved the accuracy of the CRNS soil moisture estimates.Due to the lack of low gravimetric soil moisture data,performance of the calibrated N0 function is still poor in the extremely dry conditions.Moreover,aboveground biomass including vegetation biomass,canopy interception and widely developed biological soil crusts adds to the uncertainty of the CRNS soil moisture estimates.Such biomass impacts need to be taken into consideration to further improve the accuracy of soil moisture estimation by the CRNS in the data scarce areas such as agricultural-pastoral ecotone in Northwest China.

Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes:a pilot study

Mesenchymal stem cells(MSC)have been used in clinical trials for severe diabetes,a chronic disease with high morbidity and mortality.Bone marrow is the traditional source of human MSC,but human term placenta appears to be an alternative and more readily available source.Here,the therapeutic effect of human placenta-derived MSC(PD-MSC)was studied in type 2 diabetes patients with longer duration,islet cell dysfunction,high insulin doses as well as poor glycemic control in order to evaluate the safety,efficacy and feasibility of PD-MSC treatment in type 2 diabetes(T2D).Ten patients with T2D received three intravenous infusions of PDSC,with one month interval of infusion.The total number of PDSC for each patient was(1.22–1.51)×10^(6)/kg,with an average of 1.35×10^(6)/kg.All of the patients were followed up after therapy for at least 3 months.A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU(P<0.01),and the C-peptide level was increased from 4.1±3.7 ng/mL to 5.6±3.8 ng/mL(P<0.05)respectively after therapy.In 4 of 10 responders their insulin doses reduced more than 50%after infusion.The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment(P<0.05).No fever,chills,liver damage and other side effects were reported.The renal function and cardiac function were improved after infusion.The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple,safe and effective therapeutic approach for T2D patients with islet cell dysfunction.Further large-scale,randomized and well-controlled clinical studies will be required to substantiate these observations.