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BACKGROUND@#A protocol for using human endometrium derived induced pluripotent stem cells (iPSCs) to derive hematopoietic and erythroid lineages will be elaborated, through a two-phase culture system. @*METHODS@#Discarded endometrial tissues were obtained from women receiving hysterectomy in their 4th to 5th decade due to benign uterine conditions. pCE-Sox2, Oct4, Klf4, L-Myc and Lin28 episomal vectors were used to electrotransfect the endometrial stromal cells. The first 8 days involves commitment to hematopoietic stem cells through embryoid body with robust expansion on murine bone marrow stromal cells. The second phase involves feeder free conditions with hydrocortisone, stem cell factor, interleukin-3, and recombinant EPO. After 22 days of feeder free culture, the expression profiles of CD235a+ , CD34+ , CD43+ and CD 71+ were analyzed by flow cytometry and Wright-Giemsa staining for differential counting. The oxygen carrying capacity of cultured RBCs was measured using a hemoxanalyser. @*RESULTS@#As a result of inducing these cells via co-culture with murine stromal fibroblasts, all endometrium derived iPSCs were differentiated into erythroblasts with a stable yield of approximately 80% for polychromatic and orthochromatic normoblasts. The protocol for complete induction of erythroid lineage cells starting from human endometrial tissue via iPS cells has been optimized. @*CONCLUSION@#Successful directed erythroid differentiation has occurred from human endometrium-derived iPS cells. A comprehensive process of actually deriving iPS cells using discarded surgical hysterectomy specimens to the erythroid fate has significance in that the scope of using human iPSC cell lines for tissue regeneration could be expanded in the future.
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Purpose@#We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). @*Materials and Methods@#Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. @*Results@#Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. @*Conclusion@#CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.
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Purpose@#Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. @*Materials and Methods@#This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or lifethreatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. @*Results@#Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002).No transfusion-related side effects were observed. @*Conclusion@#CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.
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Background@#Human adipose-derived mesenchymal stem cells (AMSCs) are an attractive resource for wound healing because their regenerative capacity improves injury repair. Recently, stem cell-derived exosomes have been shown to play a positive role in stem cell-based therapies. However, the effects of exosomes derived from AMSCs (AEXOs) on wound healing are unclear. In this study, we aimed to examine the role of AEXOs in attenuating inflammation and explore their effects in normal wound healing. @*Methods@#We isolated exosomes from AMSCs and established a cellular model of inflammation by treatment with the inflammatory cytokines, interferon gamma and tumor necrosis factor alpha, to determine whether AEXOs can inhibit inflammation. We examined the wound healing effects of AEXOs in in vitro wound healing models and performed a miRNA array to understand the role of AEXOs in inflammation and wound healing. @*Results@#A significant difference was observed in wound closure and the expression of anti-inflammatory and wound-healing-related factors between control and AEXO-treated cells. @*Conclusion@#Our results showed that besides alleviating the inflammation response, AEXOs also promote wound healing. Thus, AEXOs represent a novel, stem-cell-based, therapeutic strategy for wound healing.
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Purpose@#Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. @*Materials and Methods@#This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or lifethreatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. @*Results@#Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002).No transfusion-related side effects were observed. @*Conclusion@#CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.
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Background@#Human adipose-derived mesenchymal stem cells (AMSCs) are an attractive resource for wound healing because their regenerative capacity improves injury repair. Recently, stem cell-derived exosomes have been shown to play a positive role in stem cell-based therapies. However, the effects of exosomes derived from AMSCs (AEXOs) on wound healing are unclear. In this study, we aimed to examine the role of AEXOs in attenuating inflammation and explore their effects in normal wound healing. @*Methods@#We isolated exosomes from AMSCs and established a cellular model of inflammation by treatment with the inflammatory cytokines, interferon gamma and tumor necrosis factor alpha, to determine whether AEXOs can inhibit inflammation. We examined the wound healing effects of AEXOs in in vitro wound healing models and performed a miRNA array to understand the role of AEXOs in inflammation and wound healing. @*Results@#A significant difference was observed in wound closure and the expression of anti-inflammatory and wound-healing-related factors between control and AEXO-treated cells. @*Conclusion@#Our results showed that besides alleviating the inflammation response, AEXOs also promote wound healing. Thus, AEXOs represent a novel, stem-cell-based, therapeutic strategy for wound healing.
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Subject(s)
Female , Humans , Young Adult , Anemia , Antibodies , Blood Transfusion , Erythrocytes , Intellectual Disability , Iron , Isoantibodies , Korea , Mass Screening , P Blood-Group System , Phenotype , Polymerase Chain Reaction , Prevalence , Rehabilitation , Serologic TestsABSTRACT
Convalescent plasma therapy has been used to achieve passive immunization against diverse infectious agents by administering pathogen-specific antibodies. Coronavirus disease 19 (COVID-19), which originated in Wuhan, China, has recently become a major concern all over the world. There are no specific treatment recommendations for COVID-19 because of the lack of knowledge and evidence about this virus. Convalescent plasma therapy can be used as an empirical and investigational treatment for COVID-19, and so we briefly describe the main issues related to convalescent plasma therapy from the perspective of transfusion medicine.
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Purpose@#Presently, Korea is facing new challenges associated with an imbalance in blood supply and demand. The purpose ofthis study was to examine trends in blood supply and demand in Korea over the past 10 years through 2018 and to propose whatto prepare in the future. @*Materials and Methods@#Age demographics in Korea were analyzed using data from the Statistics Korea. Blood donation andblood supply data were analyzed using Blood Services Statistics 2018 by the Korean Red Cross. Blood transfusion data from hospitalsin 2018 were obtained from the Health Insurance Review and Assessment Service. @*Results@#In 2018, 2883270 whole blood and apheresis units were collected in Korea. The Korean Red Cross supplied 4277762 bloodcomponents to 2491 hospitals. The overall blood donation rate was 5.6%, and the most frequent donors were young male donors.Leukoreduced red blood cells (RBCs) constituted 25% of all RBCs used, and 40% of all platelets were supplied by single-donorplatelets. The self-sufficiency rate of domestic plasma with which to produce plasma-derived medicinal products was 68.7% in2018. Blood use was the most frequent among patients aged 70–79 years. @*Conclusion@#Blood management in Korea is changing rapidly due to a low birth rate, rapid aging, and an increase in severely illpatients who require most of the blood supply. Therefore, future plans to promote donation at a national level and optimal use ofblood in hospitals is necessary.
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.
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A 22-year old female patient with systemic lupus erythematosus presenting microangiopathic hemolytic anemia was treated with therapeutic plasma exchange 23 times. The patient's condition and laboratory findings (aspartate aminotransferase, alanine aminotransferase, ferritin, total bilirubin, and lactate dehydrogenase) did not improve despite the initial 18 therapeutic plasma exchange treatments. Thrombotic thrombocytopenic purpura was ruled out due to normal ADAMTS-13 activity test result; hemophagocytic lymphohistiocytosis was diagnosed based on fever, splenomegaly, pancytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis in bone marrow aspiration. The patient's condition improved rapidly upon treatment with a combination of immunosuppressants and cytotoxic agents, and more therapeutic plasma exchanges were performed five consecutive times with prolonged intervals in between. We observed that therapeutic plasma exchange treatment alone was not effective enough to treat hemophagocytic lymphohistiocytosis, unlike thrombotic thrombocytopenic purpura. Therefore, it is necessary to determine and start drug administration promptly in the treatment of hemophagocytic lymphohistiocytosis with thrombotic microangiopathy.
Subject(s)
Female , Humans , Alanine Transaminase , Anemia, Hemolytic , Bilirubin , Bone Marrow , Cytotoxins , Ferritins , Fever , Hypertriglyceridemia , Immunosuppressive Agents , Lactic Acid , Lupus Erythematosus, Systemic , Lymphohistiocytosis, Hemophagocytic , Pancytopenia , Plasma Exchange , Plasma , Purpura, Thrombotic Thrombocytopenic , Splenomegaly , Thrombotic MicroangiopathiesABSTRACT
Antibodies to high-incidence red blood cell antigens should be considered if panagglutination reactions are noted in all panel cells, and negative reactions to autologous red blood cells are detected on antibody screening and identification tests. In Korea, most of those antibodies are identified through international reference laboratories. To prevent a hemolytic transfusion reaction, antigen-negative red cells should be provided for those patients who have antibodies to red cell antigens. However, this is nearly impossible when the antibody has specificity to high-incidence red cell antigen. In those cases, transfusion of autologous blood, cryopreserved rare blood and the least incompatible blood components can be considered. In the case of surgery, acute normovolemic hemodilution or intraoperative blood salvage can also be considered. For the patients who have antibodies to high-incidence red cell antigens, it should be discussed to set up a national reference laboratory to quickly identify antibody specificities, and to consider establishing rare blood donor registry and frozen rare blood storage/supply system. This article reviews characteristics of antibodies to high-incidence antigens found in Koreans and also the transfusion experiences of those patients based on literature.
Subject(s)
Humans , Antibodies , Antibody Specificity , Blood Donors , Erythrocytes , Hemodilution , Isoantibodies , Korea , Mass Screening , Operative Blood Salvage , Sensitivity and Specificity , Transfusion ReactionABSTRACT
Transfusion-associated circulatory overload (TACO) is recently becoming more important than transfusion-related acute lung injury (TRALI) in terms of the number of patients with definite diagnosis as well as its prognosis. In order to diagnose TACO, it is helpful to recognize early the symptoms suspicious of transfusion reaction through electronic medical record system and computer network, and this will be of help for obtaining samples for brain natriuretic peptide (BNP) measurement before and after the onset of transfusion reaction. We report a case in which a transfusion reaction was diagnosed as TACO. A 62-year-old woman was admitted to the emergency room due to bleeding tendency. Two fresh frozen plasma units and one unit of leukocyte-reduced red blood cells were transfused. Blood pressure increased during transfusion, and the chest X-ray showed findings suggestive of newly developed pulmonary edema. N-terminal prohormone of BNP (NT-proBNP) test was carried out using the specimens in refrigerated storage. Compared with the NT-proBNP level measured 12 hours before the transfusion, that measured 6 hours after the transfusion was markedly increased (>48 fold of pre-transfusion level). As a result, this case was diagnosed with TACO.
Subject(s)
Female , Humans , Middle Aged , Acute Lung Injury , Blood Pressure , Diagnosis , Electronic Health Records , Emergency Service, Hospital , Erythrocytes , Hemorrhage , Natriuretic Peptide, Brain , Plasma , Prognosis , Pulmonary Edema , Thorax , Transfusion ReactionABSTRACT
BACKGROUND@#Transfusion-related acute lung injury (TRALI) is defined as acute respiratory distress syndrome with non-cardiogenic pulmonary edema caused by transfusion. It occurs only rarely but could result in patient mortality. TRALI has been declining since the successful adoption of TRALI risk mitigation strategies in several countries. The new diagnostic criteria were suggested in 2019 based on the knowledge and experience gained throughout the last decade. This article integrated a series of TRALI cases diagnosed in a tertiary hospital while reviewing each case based upon the new diagnostic criteria.@*METHODS@#Among the reported transfusion adverse reactions that occurred from March 2013 to June 2019, seven TRALI cases were recruited for this study. Each case was retrospectively reexamined with its clinical condition and transfusion history. The diagnosed cases were classified into TRALI subtypes newly suggested in the 2019 version.@*RESULTS@#The mean time interval to adverse reaction was 117 minutes (range: 7~370 minutes) and all satisfied the condition of hypoxemia and bilateral pulmonary infiltrations. The transfused blood components were apheresis platelets in three cases, platelet concentrates in one case, red blood cells in one case and combinations of different products in two cases. Five cases were diagnosed as possible TRALI, and all five cases were diagnosed as TRALI type 2 (2019 criteria).@*CONCLUSION@#In our center, seven patients were diagnosed TRALI during the last 6 years. Screening more TRALI patients according to the new criteria, along with investigating the patients' clinical characteristics, transfused blood components, treatments and integrated research, will facilitate Korean research on this field of medicine.
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BACKGROUND/AIMS: Although several studies have suggested that tooth loss is associated with the risk of gastric cancer, the association between oral health and gastric cancer remains a controversial issue. Thus, we investigated whether oral health is associated with the risk of gastric neoplastic lesions. MATERIALS AND METHODS: We retrospectively evaluated 391 patients who underwent upper gastrointestinal endoscopic examination between March 2010 and February 2013. The tooth number and the age-related periodontal bone loss score (ArB score) were investigated as parameters of oral health. Gastric neoplastic lesions included adenomas and cancer detected on biopsy examination. RESULTS: We identified 10 patients (2.6%) with neoplastic lesions. Older age, a higher body mass index, and the presence of Helicobacter pylori infection were significantly associated with neoplastic lesions. However, there was no significant correlation about Kimura-Takemoto classification, ArB score, and tooth number. Multivariate analyses showed that age was significantly associated with neoplastic lesions. CONCLUSIONS: Our findings demonstrate that oral health (assessed using parameters such as tooth number and ArB score) may not be significantly associated with gastric neoplastic lesions.
Subject(s)
Humans , Adenoma , Alveolar Bone Loss , Biopsy , Body Mass Index , Classification , Helicobacter pylori , Multivariate Analysis , Oral Health , Retrospective Studies , Stomach Neoplasms , Tooth , Tooth LossABSTRACT
In this study, we report a case of anti-Gerbich (Ge) alloantibody to a high-prevalence Ge antigen in a donor with Fy(a−b−) phenotype. The alloantibody was detected in an Emirati boy who was admitted to a Korean tertiary hospital for marrow hematopoietic progenitor cell donation. He did not have a history of transfusion. His blood type was A, RhD+, and findings from the antibody screening and identification test showed 2+ reactivity in all panel cells except autologous cells. We concluded that it would be very difficult to find compatible blood components for the donor and requested further tests from external laboratories. Anti-Ge2 was identified by additional tests in a foreign reference laboratory, and the Duffy genotype of the donor was FY*02/FY*02N.01 based on the Korean Rare Blood Program. Although the donor was not a Korean, as the number of foreign patients visiting Korea increases annually, there is growing interest in patients with rare blood types in the Korean population. However, there has been very little research on rare or high prevalence blood type antigen and antibody in the Korean population. Therefore, additional research in Korea is needed on rare blood group antibodies and antigens, including Ge cases.
Subject(s)
Humans , Male , Antibodies , Bone Marrow , Genotype , Hematopoietic Stem Cells , Korea , Mass Screening , Phenotype , Prevalence , Tertiary Care Centers , Tissue DonorsABSTRACT
A 72-year-old man with general weakness visited the outpatient clinic of the hematology department. The patient had been treated under the diagnosis of autoimmune hemolytic anemia for 2 years. His hemoglobin level at the time of the visit was 6.3 g/dL, and a blood transfusion was requested to treat his anemia. The patient's blood type was A, RhD positive. Antibody screening and identification test showed agglutination in all reagent cells with a positive reaction to autologous red blood cells (RBCs). He had a prior transfusion history with three least incompatible RBCs. The patient returned home after receiving one unit of leukoreduced filtered RBC, which was the least incompatible blood in the crossmatching test. After approximately five hours, however, fever, chills, dyspnea, abdominal pain, and hematuria appeared and the patient returned to the emergency room next day after the transfusion. The anti-Fy(a) antibody, which was masked by the autoantibody, was identified after autoadsorption using polyethylene glycol. He was diagnosed with an acute hemolytic transfusion reaction due to anti-Fy(a) that had not been detected before the transfusion. In this setting, it is necessary to consider the identification of coexisting alloantibodies in patients with autoantibodies and to become more familiar with the method of autoantibody adsorption.
Subject(s)
Aged , Humans , Abdominal Pain , Adsorption , Agglutination , Ambulatory Care Facilities , Anemia , Anemia, Hemolytic, Autoimmune , Autoantibodies , Blood Transfusion , Chills , Diagnosis , Dyspnea , Emergency Service, Hospital , Erythrocytes , Fever , Hematology , Hematuria , Isoantibodies , Masks , Mass Screening , Methods , Polyethylene Glycols , Transfusion ReactionABSTRACT
Here, we report two cases of identified anti-Di(b) antibodies with rare Di(a+b−) blood types from two different hospitals in Korea. Di(b) mismatched transfusion could cause a hemolytic transfusion reaction. However, it is extremely difficult to find compatible blood for patients with such a rare blood type. In this regard, we concluded that national level rare donor registry program, wherein rare blood types are indexed, needs to be established. Moreover, laboratory medicine specialists at each hospital should encourage donor registration and family testing through education for helping patients with rare blood types. These efforts will help establish a system that guarantees safe blood transfusion for patients.
Subject(s)
Humans , Antibodies , Blood Donors , Blood Transfusion , Education , Korea , Phenotype , Specialization , Tissue Donors , Transfusion ReactionABSTRACT
BACKGROUND: Grafts survive despite blood group antigens on the transplant being continuously exposed to antibodies in the blood of recipients in ABO-incompatible kidney transplantation (ABOi KT), owing to the mechanism of accommodation. We analyzed the immunodynamics of soluble ABH antigens in allografts from secretor donors and the influence of such immunodynamics on accommodation and subsequent graft survival in ABOi KT. METHODS: The genotype of a known human β-galactoside α-1,2-fucosyltransferase gene (FUT2), which determines soluble ABH antigen secretor status, was established in 32 donors for ABOi KT at the Severance Hospital, from June 2010 to July 2015. Clinical outcomes of recipients, such as anti-A/B antibody titer change, renal function, and graft survival, were evaluated. RESULTS: Twenty-five donors were secretors (78.1%), and seven were nonsecretors (21.9%). The frequency of anti-A/B IgG or IgM antibody titer elevation or reduction post-transplantation was not significantly related to donor secretor status. However, IgM titer was rapidly reduced in recipients transplanted from nonsecretor donors (P=0.01), which could be explained by the lack of absorption effect of soluble antigens, enhancing the binding of antibodies to antigens in the allografts. Interestingly, soluble ABH antigens did not affect rejection-free graft survival, which may be due to the nature of β-galactoside α-1,2-fucosyltransferase. CONCLUSIONS: Soluble ABH antigens produced by transplanted kidneys from secretor donors played a role in inducing accommodation within three months of KT through neutralization; however, major graft outcomes were not affected.