BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant.Long term cryopreservation is commonly defined as five years or longer,and limited da...BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant.Long term cryopreservation is commonly defined as five years or longer,and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft.Clinical programs,stem cell banks,and regulatory and accrediting agencies interested in product stability would benefit from such data.Thus,we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2 Rγnull(NSG)mice.AIM To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units.METHODS PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health.These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice,and the pre-freeze and post-thaw characteristics of the units were compared.Progenitor function was assessed using standard colony-forming assays.CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function.RESULTS Ten PBSC units with mean of 17 years in cryopreservation(range 13.6-18.3 years)demonstrated a mean total cell recovery of 88%±12%(range 68%-110%)and post-thaw viability of 69%±17%(range 34%-86%).BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw.Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units.All mice demonstrated long-term engraftment at 12 wk with mean34%±24%human CD45+cells,and differentiation with presence of human CD19+,CD3+and CD33+cells.Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies.CONCLUSION We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice,signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.展开更多
Objective:Patients undergoing hematopoietic stem cell transplant(HSCT)need frequent transfusions,until their red blood cells(RBCs)and platelets start to recover.The safe transfusion for patients who receive ABO-incomp...Objective:Patients undergoing hematopoietic stem cell transplant(HSCT)need frequent transfusions,until their red blood cells(RBCs)and platelets start to recover.The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process.To date,there is no user-friendly tool to choose the right blood product for transfusion treatment,despite the number of guidelines and expert advice on the subject.Methods:R/shiny is a powerful programming language for clinical data analysis and visualization.It can create interactive web applications that work in real-time.The web application named TSR was built using R programming,simplifying blood transfusion practice for ABO-incompatible HSCT witha one-click solution.Results:The TSR is divided into four main tabs.The home tab provides an overview of the application,while RBC,plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category.Unlike traditional methods that rely on treatment guidelines and specialist consensus,TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters,providing an innovative approach to improve transfusion support.Conclusion:The present study highlights that the TSR enables real-time analysis,and promotes transfusion practice byoffering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT.TSR has the potential to become a widely-utilized tool for transfusion services,providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.展开更多
Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients wit...Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days . On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA)by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ventricular beats ,ventricular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4%(10/41), including bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.展开更多
Background: Autologous peripheral blood hematopoietic stem cell transplantation is widely used in the treatment of malignant lymphoma. Patients are prone to infection during the transplantation immune deficiency perio...Background: Autologous peripheral blood hematopoietic stem cell transplantation is widely used in the treatment of malignant lymphoma. Patients are prone to infection during the transplantation immune deficiency period. There has been a lot of clinical research into how to better manage this period of vulnerability. Objective: This study aims to investigate the efficacy of 2% chlorhexidine gluconate (CHG) for skin disinfection in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) and observe any adverse reactions. Methods: A total of 106 patients receiving autologous hematopoietic stem cell transplantation from November 2019 to December 2020 in our district were selected as the control group. From January 2021 to January 2022, 106 patients with autologous hematopoietic stem cells were included in the experimental group. The control group used the immersion bath method. The experimental group was treated with an improved scrub bath method (including 3M 2% chlorhexidine gluconate medical sanitary wipes to wipe the whole skin once). Results: The bacteria-carrying rate of the improved method (37.74%) was significantly better than that of the traditional soaking method (72.64%), and the difference was statistically significant (P Conclusion: The improved bath/wipe method has a significant positive effect on skin disinfection for patients undergoing HSCT.展开更多
BACKGROUND The understanding regarding genetic variation,pathophysiology,and complications associated with pyruvate kinase deficiency(PKD)in red blood cells has been explained largely,and supportive treatment is curre...BACKGROUND The understanding regarding genetic variation,pathophysiology,and complications associated with pyruvate kinase deficiency(PKD)in red blood cells has been explained largely,and supportive treatment is currently the main management strategy.Etiotropic managements,including transplantation and genome editing,supplying for substitute dugs of the pyruvate kinase,are all under research.CASE SUMMARY We herein report a 3-year-old boy with severe transfusion-dependent PKD cured by unrelated identical peripheral blood stem cell transplantation(PBSCT).Hemoglobin was corrected to a normal level by gene correction after PBSCT,with no complication related to the transplantation.CONCLUSION Hematopoietic stem cell transplantation could be a substitute for transfusiondependent PKD.展开更多
Objective To study the toxic effects of 5-amionlevulinic acid-based photodynamic therapy (ALA-PDT) on human peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells (CBMCs) and peripheral blood stem ce...Objective To study the toxic effects of 5-amionlevulinic acid-based photodynamic therapy (ALA-PDT) on human peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells (CBMCs) and peripheral blood stem cells (PBSCs), and furthermore, to understand the possible causes of this response. Methods We used MTT assay to detect the survival rate of PBMCs, CBMCs and PBSCs after treated by ALA-PDT under the optimum experiment conditions with U937 as control; Annexin V-FITC/PI was used to detect the pattern of cell death induced by ALA-PDT. By using flow cytometry, we detected intracellular PpIX fluorescence intensity. Results After ALA-PDT treatment the survival rate of PBMCs had no significant change; however in PBSCs and CBMCs, the survival rate reduced to 70%, and the survival rate of leukemia cell U937 was the lowest, about 30%. After incubation with ALA, except for PBMCs, intracellular PpIX fluorescence intensity of the other two kinds of normal haemocytes and U937 increased obviously. These results combined with the flow cytometry suggested that the main pattern of cell death here was apoptosis. Conclusion Under the optimum experiment conditions, ALA-PDT has a slight effect on normal haemocytes but excellent depletions of leukemia cells. Therefore, it can effectively purify autologous bone marrow or stem cell grafts.展开更多
Comparative studies of the properties of murine haemopoietic stem cells from differentsources revealed that the peripheral haemopoietic stem cell is relatively weaker than the haemo-poietic stem cell from bone marrow ...Comparative studies of the properties of murine haemopoietic stem cells from differentsources revealed that the peripheral haemopoietic stem cell is relatively weaker than the haemo-poietic stem cell from bone marrow in promoting the recovery of hemopoiesis in the irradiatedanimals. This is due to the heterogenity of stem cell population in which some aged cellsub-populations aro co-existing. The modified potential in proliferation and differentiation ofhaemopoietic stem cells in the peripheral blood seems to be irreversible under normal physio-logical conditons.In a preliminary experiment, the use of an anti-thymocyte immunoglob-ulin to eliminate immunocompetent cells proved effective in reducing the severity and incidenceof secondary diseases and in increasing the number of survivors of lethally irradiated semi-isologous mice after transplantation of parental peripheral mononuclear cells.展开更多
BACKGROUND Osteochondritis dissecans(OCD)is a rare disease of unclear cause characterized by subchondral bone damage and overlying cartilage defects.The current report presents the results of subchondral bone as a nov...BACKGROUND Osteochondritis dissecans(OCD)is a rare disease of unclear cause characterized by subchondral bone damage and overlying cartilage defects.The current report presents the results of subchondral bone as a novel target for implantation of peripheral blood stem cells(PBSCs)in the treatment of OCD.CASE SUMMARY A 16-year-old patient diagnosed with OCD underwent subchondral bone implantation of PBSCs.Four months later,the patient's visual analog scale scores,Western Ontario and McMaster University osteoarthritis index,and whole-organ magnetic resonance imaging score improved significantly,and regeneration of cartilage and subchondral bone was observed on magnetic resonance imaging.CONCLUSION This is the first case of OCD treated with subchondral bone as an implantation target of PBSCs,which highlights the importance of subchondral bone for cartilage repair.This treatment could be a potential option for articular cartilage and subchondral bone recovery in OCD.展开更多
基金Supported by a pilot grant from the Indiana University Center of Excellence in Molecular Hematology,NIDDK,No.P30DK090948(to Hege KM and Goebel WS)the NIH/NCI Cancer Center,No.P30CA082709 awarded to the Indiana University Simon Comprehensive Cancer Center(to Sinn A and Pollok KE)。
文摘BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant.Long term cryopreservation is commonly defined as five years or longer,and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft.Clinical programs,stem cell banks,and regulatory and accrediting agencies interested in product stability would benefit from such data.Thus,we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2 Rγnull(NSG)mice.AIM To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units.METHODS PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health.These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice,and the pre-freeze and post-thaw characteristics of the units were compared.Progenitor function was assessed using standard colony-forming assays.CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function.RESULTS Ten PBSC units with mean of 17 years in cryopreservation(range 13.6-18.3 years)demonstrated a mean total cell recovery of 88%±12%(range 68%-110%)and post-thaw viability of 69%±17%(range 34%-86%).BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw.Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units.All mice demonstrated long-term engraftment at 12 wk with mean34%±24%human CD45+cells,and differentiation with presence of human CD19+,CD3+and CD33+cells.Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies.CONCLUSION We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice,signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.
文摘Objective:Patients undergoing hematopoietic stem cell transplant(HSCT)need frequent transfusions,until their red blood cells(RBCs)and platelets start to recover.The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process.To date,there is no user-friendly tool to choose the right blood product for transfusion treatment,despite the number of guidelines and expert advice on the subject.Methods:R/shiny is a powerful programming language for clinical data analysis and visualization.It can create interactive web applications that work in real-time.The web application named TSR was built using R programming,simplifying blood transfusion practice for ABO-incompatible HSCT witha one-click solution.Results:The TSR is divided into four main tabs.The home tab provides an overview of the application,while RBC,plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category.Unlike traditional methods that rely on treatment guidelines and specialist consensus,TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters,providing an innovative approach to improve transfusion support.Conclusion:The present study highlights that the TSR enables real-time analysis,and promotes transfusion practice byoffering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT.TSR has the potential to become a widely-utilized tool for transfusion services,providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.
文摘Objective Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with AMI, but the safety of intracoronory infusion of autologous peripheral blood stem-cell(PBSCs) in patients with AMI is unknown. For this reason, we observe the feasibility and safety of PBSCs transplantation by intracoronory infusion in such patients.Method Fourty one patients with AMI were allocated to receive Granulocyte Colony-Stimulating Factor (G-CSF:Filgrastim,300 μg) with the dose of 300 μg-600 μg/day to mobilize the stem cell, and the duration of applying G-CSF was 5 days . On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then the suspend liquid was infused into the infarct related artery (IRA)by occluding the over the wire balloon and infusing artery through balloon center lumen. In the process of the intracoronary infusion of PBSCs, the complications should be observed, which were arrhythmias including of bradycardia, sinus arrest or atrial ventricular block, premature ventricular beats ,ventricular tachycardia, ventricular fibrillation; and hypotention, etc. Results There were total 10 cases with complications during the intracoronary infusion of PBSCs. The incidence of complications was 24.4%(10/41), including bradycardia is 2.4 %(1/41), sinus arrest or atrial ventricular block is 4.9%(2/41), ventricular fibrillation is 2.4 %( 1/41), hypotention is14.6 % (6 /41).Conclusions In patients with AMI, intracoronary infusion of PBSCs is feasible and safe.
文摘Background: Autologous peripheral blood hematopoietic stem cell transplantation is widely used in the treatment of malignant lymphoma. Patients are prone to infection during the transplantation immune deficiency period. There has been a lot of clinical research into how to better manage this period of vulnerability. Objective: This study aims to investigate the efficacy of 2% chlorhexidine gluconate (CHG) for skin disinfection in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) and observe any adverse reactions. Methods: A total of 106 patients receiving autologous hematopoietic stem cell transplantation from November 2019 to December 2020 in our district were selected as the control group. From January 2021 to January 2022, 106 patients with autologous hematopoietic stem cells were included in the experimental group. The control group used the immersion bath method. The experimental group was treated with an improved scrub bath method (including 3M 2% chlorhexidine gluconate medical sanitary wipes to wipe the whole skin once). Results: The bacteria-carrying rate of the improved method (37.74%) was significantly better than that of the traditional soaking method (72.64%), and the difference was statistically significant (P Conclusion: The improved bath/wipe method has a significant positive effect on skin disinfection for patients undergoing HSCT.
文摘BACKGROUND The understanding regarding genetic variation,pathophysiology,and complications associated with pyruvate kinase deficiency(PKD)in red blood cells has been explained largely,and supportive treatment is currently the main management strategy.Etiotropic managements,including transplantation and genome editing,supplying for substitute dugs of the pyruvate kinase,are all under research.CASE SUMMARY We herein report a 3-year-old boy with severe transfusion-dependent PKD cured by unrelated identical peripheral blood stem cell transplantation(PBSCT).Hemoglobin was corrected to a normal level by gene correction after PBSCT,with no complication related to the transplantation.CONCLUSION Hematopoietic stem cell transplantation could be a substitute for transfusiondependent PKD.
基金supported by the National Natural Science Foundation of China (No.60178034)Doctor Thesis Founda-tion of Xi an Jiaotong University (No. DFXJTU2002-2) .
文摘Objective To study the toxic effects of 5-amionlevulinic acid-based photodynamic therapy (ALA-PDT) on human peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells (CBMCs) and peripheral blood stem cells (PBSCs), and furthermore, to understand the possible causes of this response. Methods We used MTT assay to detect the survival rate of PBMCs, CBMCs and PBSCs after treated by ALA-PDT under the optimum experiment conditions with U937 as control; Annexin V-FITC/PI was used to detect the pattern of cell death induced by ALA-PDT. By using flow cytometry, we detected intracellular PpIX fluorescence intensity. Results After ALA-PDT treatment the survival rate of PBMCs had no significant change; however in PBSCs and CBMCs, the survival rate reduced to 70%, and the survival rate of leukemia cell U937 was the lowest, about 30%. After incubation with ALA, except for PBMCs, intracellular PpIX fluorescence intensity of the other two kinds of normal haemocytes and U937 increased obviously. These results combined with the flow cytometry suggested that the main pattern of cell death here was apoptosis. Conclusion Under the optimum experiment conditions, ALA-PDT has a slight effect on normal haemocytes but excellent depletions of leukemia cells. Therefore, it can effectively purify autologous bone marrow or stem cell grafts.
文摘Comparative studies of the properties of murine haemopoietic stem cells from differentsources revealed that the peripheral haemopoietic stem cell is relatively weaker than the haemo-poietic stem cell from bone marrow in promoting the recovery of hemopoiesis in the irradiatedanimals. This is due to the heterogenity of stem cell population in which some aged cellsub-populations aro co-existing. The modified potential in proliferation and differentiation ofhaemopoietic stem cells in the peripheral blood seems to be irreversible under normal physio-logical conditons.In a preliminary experiment, the use of an anti-thymocyte immunoglob-ulin to eliminate immunocompetent cells proved effective in reducing the severity and incidenceof secondary diseases and in increasing the number of survivors of lethally irradiated semi-isologous mice after transplantation of parental peripheral mononuclear cells.
文摘BACKGROUND Osteochondritis dissecans(OCD)is a rare disease of unclear cause characterized by subchondral bone damage and overlying cartilage defects.The current report presents the results of subchondral bone as a novel target for implantation of peripheral blood stem cells(PBSCs)in the treatment of OCD.CASE SUMMARY A 16-year-old patient diagnosed with OCD underwent subchondral bone implantation of PBSCs.Four months later,the patient's visual analog scale scores,Western Ontario and McMaster University osteoarthritis index,and whole-organ magnetic resonance imaging score improved significantly,and regeneration of cartilage and subchondral bone was observed on magnetic resonance imaging.CONCLUSION This is the first case of OCD treated with subchondral bone as an implantation target of PBSCs,which highlights the importance of subchondral bone for cartilage repair.This treatment could be a potential option for articular cartilage and subchondral bone recovery in OCD.