Número de células CD34+ circulantes como predictor de recolección exitosa de progenitores hematopoyéticos por aféresis en trasplante autólogo / Number of circulating CD34+ cells as a predictor of successful collection of hematopoietic progenitors by apheresis in autologous transplantation

RESUMEN Introducción. El trasplante autólogo de células progenitoras hematopoyéticas es una terapia eficaz en neoplasias malignas hematológicas. El número de células que CD34+ en sangre periférica es el mejor predictor del rendimiento de recolección de células progenitoras hematopoyéticas. Objetivo. Determinar el número de células CD34+ en sangre periférica asociado al éxito de recolección de progenitores hematopoyéticos por aféresis en trasplante autólogo. Métodos. Se evaluó retrospectivamente los datos de 236 procedimientos de aféresis de células progenitoras hematopoyéticas para el trasplante autólogo en el Hospital Edgardo Rebagliati Martins (Lima, Perú) de julio del 2020 a julio del 2023. Se utilizó la curva ROC (características operativas del receptor) para determinar el número de células CD34+ en sangre periférica necesario para lograr una recolección por aféresis ≥ 2 x 106 células CD34+/kg. Resultados. El 61% fueron hombres, con mediana de edad de 58 años, el valor de corte fue de 18,38 células CD34+/μL (sensibilidad de 94,1% y especificidad de 96,9%). Conclusión. El número de células CD34+ sangre periférica para una recolección exitosa de células progenitoras hematopoyéticas para el trasplante autólogo fue de 18,38 células CD34+/μL.

ABSTRACT Introduction. Autologous hematopoietic progenitor cell transplantation is an effective therapy in hematological malignancies, the number of CD34+ cells in peripheral blood is the best predictor of hematopoietic progenitor cell harvesting performance. Objective. To determine the number of CD34+ cells in peripheral blood associated with the successful collection of hematopoietic progenitors by apheresis in autologous transplantation. Methods. The data of 236 hematopoietic progenitor cell apheresis procedures for autologous transplantation at the Edgardo Rebagliati Martins Hospital (Lima, Peru) were retrospectively evaluated from July 2020 to July 2023. The ROC (receiver operating characteristics) curve was used to determine the number of CD34+ cells in peripheral blood necessary to achieve an collection by apheresis ≥ 2 x 106 CD34+ cells/kg. Results. 61% were men, with a median age of 58 years, the cut-off value was 18.38 CD34+ cells/μL (sensitivity of 94.1% and specificity of 96.9%). Conclusion. The number of peripheral blood CD34+cells for successful collection of hematopoietic progenitor cells for autologous transplantation was 18.38 CD34+ cells/μL.

Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso / Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Mechanism of Xibining Ⅱ Combined with ADSC-Exos in Improving Knee Osteoarthritis by Regulating Mitochondrial Autophagy / 中国实验方剂学杂志

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.

Application of mesenchymal stem cell therapy in kidney transplantation: a continued story / 器官移植

Immunosuppressant is one of the main preventive measures for rejection after organ transplantation, whereas it may reduce the host response capability to pathogens and increase the risk of infection. In recent years, the application of mesenchymal stem cell (MSC) therapy in the field of solid organ transplantation has attracted widespread attention. Preclinical studies have shown that MSC therapy may prolong the survival time of transplant kidney, induce immune tolerance, accelerate the repair of acute kidney injury and promote the recovery of renal function. Clinical trials have confirmed the safety, tolerance and effectiveness of MSC therapy. Consequently, general characteristics, immunomodulation and tissue repair function of MSC, and the application of MSC in clinical trials of kidney transplantation were reviewed, the unresolved issues were briefly discussed and the prospects for subsequent research were predicted, aiming to provide reference for promoting the application of MSC therapy in clinical kidney transplantation.

Clinical analysis of lung transplantation for lung chronic graft-versus-host disease after hematopoietic stem cell transplantation / 器官移植

<b>Objective</b> To evaluate clinical efficacy of lung transplantation for lung chronic graft-versus-host disease (cGVHD) after hematopoietic stem cell transplantation (HSCT). <b>Methods</b> Clinical data of 12 patients undergoing lung transplantation for lung cGVHD were retrospectively analyzed. Preoperative clinical manifestations and involved organs of patients were analyzed. The lung function before and after lung transplantation was compared, and the survival of patients after lung transplantation was analyzed. <b>Results</b> Eleven patients underwent HSCT due to primary hematological malignancies, including 9 cases of leukemia, 1 case of myelodysplastic syndrome, 1 case of lymphoma. And 1 case underwent HSCT for systemic lupus erythematosus. Among 12 cGVHD patients, skin involvement was found in 8 cases, oral cavity involvement in 5 cases, gastrointestinal tract involvement in 4 cases and liver involvement in 3 cases. All 12 patients developed severe respiratory failure caused by cGVHD before lung transplantation, including 9 cases of typeⅡ respiratory failure and 3 cases of type Ⅰ respiratory failure. Two patients underwent right lung transplantation, 2 cases of left lung transplantation and 8 cases of bilateral lung transplantation. The interval from HSCT to lung transplantation was 75 (19-187) months. Upon the date of submission, postoperative follow-up time was 18 (7-74) months. Ten patients survived, 1 died from severe hepatitis at postoperative 22 months, and 1 died from gastrointestinal bleeding at postoperative 6 months. No recurrence of primary diseases was reported in surviving patients. <b>Conclusions</b> Lung transplantation is an efficacious treatment for lung cGVHD after HSCT, which may prolong the survival time and improve the quality of life of the recipients.

Research progress and existing problems in the industrialization of stem cell drugs / 中国药科大学学报

@#Abstract: Stem cells, which are a type of primitive cells with multipotent differentiation potential and self-renewal ability, have the potential to regenerate various tissues and organs. Stem cell drug development is a frontier research field in life sciences. Extensive clinical trials involving stem cells have been conducted for different complicated diseases. Some stem cells have been approved as drugs for some indications, indicating their broad industrial prospects. This review introduces the progress of stem cell drugs around the world, especially in China, and discusses the main problems in the industrialization of stem cell drugs, such as their effectiveness, quality control and safety, so as to provide some reference and insight for the development and rapid industrialization of stem cell drugs.

Repairment effect of intra-articular adipose stem cell injection on articular cartilage destruction in rabbit model with temporomandibular joint osteoarthritis and its mechanism / 吉林大学学报(医学版)

Objective:To discuss the repairment effect of intra-articular injection of adipose derived stem cells(ADSCs)on articular cartilage destruction in the temporomandibular joint osteoarthritis(TMJOA)model rabbits,and to clarify the possible mechanism.Methods:Twenty-seven rabbits were randomly divided into control group,model group,and ADSCs group.The ADSCs of the rabbits were extracted and cultured.The rabbit TMJOA model was prepared by monosodium-iodoacetate(MIA)injection technique.The temporomandibular joint cavity of the TMJOA model rabbits in ADSCs group was given two continuous intra-articular injections of 1.0×106 mL-1 ADSCs,while the rabbits in control and model group were given sequivalent volume of saline into the temporomandibular joint cavity.After 8 weeks,Micro-CT scan was performed on the temporomandibular joints of the rabbits in various groups;the bone volume fraction(BV/TV),bone surface area/bone volume(BS/BV),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular number(Tb.N)of condyles tissue of the rabbits in various groups were analyzed;HE staining was used to observe the pathomorphology of condyles tissue of the rabbits in various groups;immunohistochemistry was used to detect the localization and expression levels of SRY-related high mobility group box gene 9(SOX9),matrix metalloproteinase-13(MMP-13),and vascular endothelial growth factor(VEGF)proteins in condyles tissue of the rabbits in various groups;Western blotting method was used to detect the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in various groups.Results:The micro-CT scan results showed that compared with control group,the BV/TV,Tb.Th,and Tb.N of condyles tissue of the rabbits in model group were significantly decreased(P<0.05),while the BS/BV and Tb.Sp were significantly increased(P<0.05);compared with model group,the BV/TV,Tb.Th,and Tb.N in condyles tissue of the rabbits in ADSCs group were significantly increased(P<0.05),and the BS/BV and Tb.Sp were significantly decreased(P<0.05).The HE staining results showed that the condylar cartilage surface of the rabbits in control group was smooth with clear layers and intact structure;compared with control group,the surface of condyles tissue of the rabbits in model group was irregular with thickened hypertrophic layer and areas of cell depletion and clustering;compared with model group,the pathological damage of condyles tissue of the rabbits in ADSCs group was significantly decreased.The immunohistochemical staining results showed that compared with control group and ADSCs group,the number of brown granule in condyles tissue of the rabbits in model group was increased,mainly concentrated in the hypertrophic layer,especially in the bone cartilage junction site and the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the number of brown granule in condyles tissue of the rabbits in ADSCs group was significantly decreased,and the expression levels of SOX9,MMP-13,and VEGF proteins were significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in ADSCs group were significantly decreased(P<0.05).Conclusion:Intra-articular injection of ADSCs can effectively repair the cartilage destruction in TMJOA,alleviate the cartilage injury,and mitigate the progression of osteoarthritis.

Effect of culture supernatant of human umbilical cord mesenchymal stem cells on survival,apoptosis and endometrium receptivity of human endometrial stromal cells after treated with mifepristone / 吉林大学学报(医学版)

Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.

Diagnosis and treatment progress of liver injury after allogeneic hematopoietic stem cell transplantation / 白血病·淋巴瘤

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative method for various hematological diseases. With the optimization of transplantation technology, the clinical application of allo-HSCT is more and more mature. Post-transplant liver injury is one of the common postoperative complications, which seriously affects the quality of life and long-term survival of patients. The causes of liver injury after allo-HSCT can be divided into non-infectious and infectious factors, which show similar clinical manifestations and different treatment principles. Timely diagnosis of post-transplant liver injury and the identification of the disease cause will be beneficial for early prevention or targeted treatment, thereby improving patients' prognosis. This review focuses on the etiology, clinical features, and treatment options of liver injury after allo-HSCT, aiming to deepen the understanding of hematologists on liver injury after allo-HSCT.

Clinical analysis of metagenome next-generation sequencing for diagnosing invasive fungal disease in patients with early stage of hematopoietic stem cell transplantation / 陆军军医大学学报

Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

Effects of anti-HLA donor-specific antibodies and desensitization on engraftment of haploidentical hematopoietic stem cell transplantation / 陆军军医大学学报

Objective To investigate the effects of anti-HLA donor-specific antibodies(DSA)and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed.Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies,15(21.4％)patients were DSA positive,including 7(46.7％)cases of strong positive,3(20.0％)cases of moderate positive,and 5(33.3％)cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients(P=0.027).For the 6 patients developed graft failure(GF),4 were DSA+which was statistically higher than the DSA-patients(P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF(HR=9.273,95％CI:1.505～57.124,P=0.016).Among the 10 patients(7 strong positive and 3 moderate positive DSA)received desensitization therapy,4 patients received combination desensitization,with a 100％rate of successful transplantation,and 6 received single desensitization,with 4(66.7％)experiencing GF,so the GF rate was obviously lower in the combination than the single desensitization(P=0.008).Conclusion In haplo-HSCT patients,DSA is an important factor leading to implantation delay and GF.While,single desensitization treatment has limited efficacy.In combined DSA desensitization therapy,the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

Association of intestinal and oral microbiota with acute graft versus host disease of the gastrointestinal tract in patients after allogeneic hematopoietic stem cell transplantation / 陆军军医大学学报

Objective To preliminarily investigate the association between changes in intestinal microbiota and oral microbiota of allogeneic hematopoietic stem cell transplantation(allo-HSCT)patients and early gastrointestinal acute graft versus host disease(aGVHD),and try to explore potentially effective biomarkers and provide theoretical basis for early prediction and intervention of gastrointestinal aGVHD.Methods Ten acute leukemia patients who developed gastrointestinal aGVHD within 1 month after receiving allo-HSCT in Department of Hematology of Sichuan Provincial People's Hospital from September 2021 to June 2023 were enrolled,and their fecal samples and saliva samples before and after the aGVHD were collected.16S rRNA sequencing analysis was applied for the differential changes in intestinal and oral microbiota before and after the development of early gastrointestinal aGVHD.Results ① A decrease in Bacteroides spp.and an increase in Enterococcus spp.and Enterobacteriaceae spp.in the intestinal microbiota were positively correlated with the occurrence of early upper gastrointestinal aGVHD(P＜0.05),whereas no significant difference was observed in the overall microbial diversity of the oral microbiota(P＞0.05).② LEfSe analysis of the intestinal microbiota before and after gastrointestinal aGVHD revealed an increase in Klebsiella spp.and Enterococcus spp.and a decrease in Escherichia coli;In the oral microbiota,LEfSe analysis revealed 10 microbial markers with significant difference,of which Gamma proteobacteria was the most significant.③ The difference in β-diversity of the intestinal microbiota was significant(P=0.03),whereas there was no significant difference in the α-and β-diversity of the oral microbiota.Conclusion Significant differences are found in intestinal microbiota before and after the occurrence of early gastrointestinal aGVHD in patients after Allo-HSCT,and the occurrence may have a correlation with the chang in oral microbiota.

Advances in treatment of acute leukemia and long-term ovarian function in children and adolescents / 国际儿科学杂志

Acute leukemia（AL）is a common hematological malignancy in children and adolescents. Chemotherapy is currently the primary treatment for AL.Alternative therapies，such as hematopoietic stem cell transplantation（HSCT），targeted therapy，and immunotherapy also offer greater hope for the survival of refractory/relapsed patients. Chemotherapeutic drugs，radiotherapy，targeted drugs and immunotherapeutic drugs are well-applied clinically，meanwhile posing threats to non-target systems. The adverse effects on the reproductive system may lead to the dilemma of infertility，thus reducing the long-term quality of life. As the survival rate of AL patients keeps increasing continuously，the influence of different treatments on the gonad function needs to be clarified. With the help of targeted fertility prevention，the patient′s quality of life can be enhanced in parallel with life span. This article aims to review the impact of AL treatment on ovarian function in female children and adolescents and provide ideas for the long-term fertility protection of leukemia patients.

The relationship between serum c-kit mRNA level and myocardial fibrosis,cardiac function and prognosis in patients with dilated cardiomyopathy complicated with heart failure / 国际检验医学杂志

Objective To investigate the relationship between serum stem cell factor receptor(c-kit)and myocardial fibrosis,cardiac function and prognosis in patients with dilated cardiomyopathy(DCM)complicat-ed with heart failure.Methods A total of 77 patients with DCM complicated with heart failure who were trea-ted in 3201 Hospital from May 2020 to June 2022 were enrolled in the study as study group,and 70 DCM pa-tients without heart failure were enrolled as the control group.The levels of serum c-kit mRNA and three my-ocardial fibrosis markers[α-smooth muscle actin(α-SMA),collagen type Ⅰ and collagen type Ⅲ]were detec-ted in the two groups.Cardiac function parameters were obtained by echocardiography.The relationship be-tween serum c-kit mRNA level and myocardial fibrosis and cardiac function was analyzed.According to the oc-currence of major adverse cardiovascular events(MACE),the patients were divided into poor prognosis group and good prognosis group.Multivariate Logistic regression analysis was used to analyze the factors affecting the prognosis of DCM patients complicated with heart failure.Receiver operating characteristic(ROC)curve was used to analyze the efficacy of serum c-kit mRNA level in predicting the prognosis of DCM patients.Results The serum c-kit mRNA level in the study group was lower than that in the control group(P＜0.05).The levels of three myocardial fibrosis indicators in the study group were higher than those in the con-trol group(P＜0.05).The left ventricular ejection fraction(LVEF)in the study group was lower than that in the control group(P＜0.05),and the left ventricular end-diastolic volume(LVEDV)and left ventricular end-systolic volume(LVESV)in the study group were higher than those in the control group(P＜0.05).Pearson correlation analysis showed that serum c-kit mRNA level was positively correlated with LVEF(r=0.677,P＜0.05),while negatively correlated with α-SMA,collagen type Ⅰ,collagen type Ⅲ,LVEDV and LVESV(r=-0.725,-0.748,-0.744,-0.745,-0.662,P＜0.05).Multivariate Logistic regression analysis showed that serum c-kit mRNA level is an independent factor for the prognosis of DCM patients with heart failure.ROC curve analysis showed that serum c-kit mRNA level had a sensitivity of 82.80％,a specificity of 81.80％,and an area under the curve of 0.829(95％CI:0.745-0.912,P＜0.001)for evaluating the progno-sis of DCM patients complicated with heart failure.Conclusion The serum c-kit mRNA level is significantly decreased in patients with DCM complicated with heart failure,and the serum c-kit mRNA level is correlated with myocardial fibrosis and cardiac function.The detection of serum c-kit mRNA level has a high efficacy in evaluating the prognosis of patients with DCM complicated with heart failure.

Effect of MSC-exo,a New Cell Delivery Tool,on Gene Delivery and Proliferation of Pancreatic Cancer / 昆明医科大学学报

Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

Application progress of mesenchymal stem cells in islet transplantation for type 1 diabetes mellitus / 器官移植

Islet transplantation is considered as one of the most effective approach for type 1 diabetes mellitus, although its efficacy is limited by several factors. Anoxia, stress and rejection occurring during the isolation, culturing and transplantation of islets may have impact on the outcome of the islet transplantation. Due to the biological properties such as anti-inflammation, angiogenetic promotion and immune regulation, mesenchymal stem cells (MSCs) are all the way focused by researchers. Additionally, exosome, a derivative of MSC, also plays an import role in regulating anoxia-induced oxidative stress modulation, angiogenetic promotion, and immune regulation. MSC-based islet transplantation may be a useful therapeutic tool in treating type 1 diabetes. Therefore, in this review, the potential effect of MSC prior and posterior to the operation of the islet transplantation, its clinical application as well as its limitations were reviewed, aiming to offer insights into the future application of islet transplantation in treating type 1 diabetes.

BMSCs promote M2 macrophage polarization to attenuate acute radiation-induced lung injury / 中国辐射卫生

Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) for radiation-induced lung injury (RILI) and the underlying mechanism. Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control, model, and BMSCs groups. The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest, while the control group did not receive X-ray irradiation. For the BMSCs group, an injection of 1 × 106 BMSCs cells was administered via the tail vein within 6 h after irradiation. In the 5th week, the lung tissue was taken to observe pathological changes with HE staining; examine the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with immunohistochemical staining; observe the polarization of macrophages with immunofluorescence staining; and measure the expression of the epithelial-mesenchymal transition markers E-cadherin, N-cadherin, and vimentin proteins by Western blot. Results After radiation, the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration, and these changes were markedly reduced in the BMSCs group. The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with significantly increased levels in the model group (P < 0.01, P < 0.05). Treatment with BMSCs significantly increased the polarization of lung macrophages towards the M2 type, while significantly decreasing the abnormally increased N-cadherin and vimentin levels in RILI mice (P < 0.05, P < 0.01). Conclusion BMSCs have therapeutic effects for RILI mice, which may be through promoting macrophage polarization from M1 to M2.

Expert Consensus on Ethical Management and Review of Stem Cell Clinical Research in Beijing Area / 中国医学伦理学

Stem cell clinical research is a hot frontier research. The ethical review of stem cell clinical research is full of challenges. Currently, clinical researches lack specific operational guidelines. Considered the related laws and regulations, and the operability of practical work, experts from the field of stem cells, such as law, ethics and management, will form a consensus on the basis of full discussion and continuous revision. It will provide reference for the operation of the ethics committee of corresponding institutions, and lay a certain foundation for the establishment of national expert consensus in the future, so as to promote the effective guidance of ethical review practice and quality evaluation of stem cell research.

Mechanism of Chir99021 regulating Wnt / β⁃catenin signaling pathway inhibiting osteogenic differentiation of rat dental pulp stem cells / 解剖学报

Objective To explore the effect and mechanism of Chir99021 on osteogenic differentiation of rat dental pulp stem cells. Methods Primary rat dental pulp stem cells were isolated from rat dental pulp and verified by fluorescence immunoassay. Different concentrations of Chir99021 were set, and the cell proliferation was detected by CCK⁃8 to select the optimal concentration. Osteogenic differentiation was detected by alizarin red staining. The expression of osteogenic differentiation related genes and proteins recombinant wingless type MMTV integration site famity member 1 (Wnt1), Wnt3a and Wnt3a β⁃expression of catenin, axis inhibition protein 2(Axin 2), dentin sialophosphoprotein(OCN) and dentin matrix acidic phosphoprotein 1(DMP1) was detected by Real⁃time PCR and Western blotting. Results The positive expression of dentin sialophosphoprotein (DSPP) and vimentin indicated that rat dental pulp stem cells were successfully isolated. After osteogenic induction of rat dental pulp stem cells, calcium deposits significantly increased with the addition of glycogen synthase kinase⁃3β(GSK⁃3β) inhibitor Chir99021, calcium deposits were significanted reduced. After osteogenic differentiation of rat dental pulp stem cells, the expression of Wnt1, Wnt3a, β⁃catenin, Axin2, OCN and DMP1 increased, while the expression of Wnt1, Axin2, OCN and DMP1 decreased with the addition of Chir99021. Conclusion Chir99021 can inhibit the osteogenic differentiation of rat dental pulp stem cells after 7 days of induction.

Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma / 中华内科杂志

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.