Advanced deep learning enables prediction of allogeneic stem cell mobilization success.

a front page story in The New York Times ([22][1]) at the end of March 2001 reported that “the basis of a possible revolution in treating heart attack patients has been laid by three reports of using stem cells from bone marrow to repair heart tissue in animals.” Those three reports ([11][2], [

Journal of HematotherapyVol. 7, No. 2 Not All Healthy Donors Mobilize Hematopoietic Progenitor Cells Sufficiently After G-CSF Administration to Allow for Subsequent CD34 Purification of the Leukapheresis ProductMette Holm and Peter HoklandMette HolmSearch for more papers by this author and Peter HoklandSearch for more papers by this authorPublished Online:27 Mar 2009https://doi.org/10.1089/scd.1.1998.7.111AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byCollecting and Processing of the GraftPBSCs Sphingoling along S1P/S1P1 axisBlood, Vol. 119, No. 3The Plasminogen System in Regulating Stem Cell MobilizationJournal of Biomedicine and Biotechnology, Vol. 2012Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics10 November 2011 | Transfusion, Vol. 51Plasminogen Regulates Stromal Cell–Derived Factor-1/CXCR4–Mediated Hematopoietic Stem Cell Mobilization by Activation of Matrix Metalloproteinase-9Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 31, No. 9Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes; a case of FVIII, FVIIa and G-CSF24 January 2010 | Expert Opinion on Drug Delivery, Vol. 7, No. 2Mobilization of Hematopoietic Cells Prior to Autologous or Allogeneic Transplantation27 November 2009Binding of proteins to PEGylated liposomes and improvement of G-CSF efficacy in mobilization of hematopoietic stem cellsJournal of Controlled Release, Vol. 135, No. 1Peripheral blood stem cell mobilization: new regimens, new cells, where do we standCurrent Opinion in Hematology, Vol. 15, No. 4Granulocyte Colony-Stimulating Factor Increases Hepatic Sinusoidal Perfusion During Liver Regeneration in Mice9 July 2009 | Journal of Investigative Surgery, Vol. 21, No. 2Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF?19 March 2007 | Bone Marrow Transplantation, Vol. 39, No. 10Rapid succession of peripheral blood progenitor cell mobilization cycles in patients with chronic heart failure: effects on the hematopoietic systemTransfusion, Vol. 46, No. 8Circulating Hematopoietic Stem Cell TransplantationNeutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GROβ/CXCL2 and GROβT /CXCL2Δ4Blood, Vol. 103, No. 1It's moving day: factors affecting peripheral blood stem mobilization and strategies for improvement23 July 2003 | British Journal of Haematology, Vol. 122, No. 3The whys and hows of hematopoietic progenitor and stem cell mobilization12 March 2003 | Bone Marrow Transplantation, Vol. 31, No. 5Plasma from poorly mobilizing human subjects inhibits cytokine-induced murine blood stem-cell mobilizationCytotherapy, Vol. 4, No. 4GM-CSF-based mobilization effect in normal healthy donors for allogeneic peripheral blood stem cell transplantation22 July 2002 | Bone Marrow Transplantation, Vol. 30, No. 2Analysis of factors associated with low peripheral blood progenitor cell collection in normal donorsTransfusion, Vol. 42, No. 1Donor age-related differences in PBPC mobilization with rHuG-CSFTransfusion, Vol. 41, No. 2Stem Cell Collection for Hematopoietic Transplantation: Stem Cell Sources, Mobilization Strategies, and Factors that Influence YieldMobilization of blood-derived stem and progenitor cells in normal subjects by granulocyte-macrophage- and granulocyte-colony-stimulating factors19 December 2002 | Transfusion, Vol. 39, No. 1 Volume 7Issue 2Apr 1998 To cite this article:Mette Holm and Peter Hokland.Not All Healthy Donors Mobilize Hematopoietic Progenitor Cells Sufficiently After G-CSF Administration to Allow for Subsequent CD34 Purification of the Leukapheresis Product.Journal of Hematotherapy.Apr 1998.111-113.http://doi.org/10.1089/scd.1.1998.7.111Published in Volume: 7 Issue 2: March 27, 2009PDF download

Osteoclasts Are Involved in Stem Cell Mobilization: Cleavage of SDF-1 by Cathepsin K.

Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 microg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 x 10(6)/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 microg/kg/day group and two patients in the 10 microg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 microg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 microg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3-4.8 x 10(6)/kg, median CFU-GM = 22.1, range = 4.2-102.9 x 10(4)/kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 microg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 microg/kg/day. However, on balance, 10 microg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation.

Diabetes impairs mobilization of stem cells for the treatment of cardiovascular disease

IntroductionExpression of haematopoietic stem and progenitor cells occurs as a result of an inflammatory reaction caused by a damaged organ. Patients undergoing coronary artery bypass surgery (CABG) using cardiopulmonary bypass (CPB) are exposed to an inflammatory reaction, which may be a trigger in the mobilization of regenerative cells.AimTo assess the impact of CPB on stem and progenitor cells mobilization in patients scheduled for CABG.Material and methodsTwenty patients with stable coronary disease, who were scheduled for CABG, were included in the study. Peripheral blood samples were collected perioperatively: 2 h before surgery, before CPB, at CPB weaning, 24 h postoperatively, and on the 6th postoperative day. Analyses of immune-labelled cells were carried out on an ImageStream (IS) system.ResultsThe following cell populations were identified during cardiac surgery: haematopoietic stem cells (HSC), mesenchymal cells (MSC), endothelial progenitors (EPC), and very small embryonic-like cells (VSEL). The profile of cell mobilization coincides with the perioperative inflammatory response. Mobilization of stem and progenitor cells induced by CPB did not occur in any of the isolated cell lines (p > 0.05). The expression profile of stem and progenitor cells was related with the inflammatory reaction associated with traumatic stress in all cell lines. Type 2 diabetes is a disease that is hampering the trend of MSC mobilization.ConclusionsMobilization of haematopoietic stem and progenitor cells was not related with CPB. The inflammatory reaction was associated with perioperative trauma. Cell release was inhibited in patients with diabetes.

Impact of Daratumumab-Containing Induction Therapy on Stem Cell Mobilization in Multiple Myeloma: A Retrospective, Single-Center Analysis

Monocytosis and neutrophilia are well-established risk factors for atherosclerosis and seem to play a causative role in lesion development. Studies in mice with defects in cholesterol efflux pathways have identified novel roles for the ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and apolipoprotein E in suppressing hematopoietic stem cell proliferation, mobilization, and the production of monocytes and neutrophils in the bone marrow. In addition, stem cell mobilization to the spleen initiates extramedullary hematopoiesis, which acts as a monocytic reservoir. Increased monocyte and neutrophil levels drive atherogenesis and its complications. Increasing high-density lipoprotein levels and cholesterol efflux can reverse excessive myelopoiesis and stem cell mobilization, suggesting a novel antiatherogenic effect of some forms of high-density lipoprotein elevation. After a myocardial infarction, splenic Ly-6C(hi) monocyte populations are sustained by a second wave of stem cell mobilization from the bone marrow and continue to enter atheroma, accelerating atherogenesis. Because activation of cholesterol efflux pathways can inhibit stem cell proliferation, mobilization, and monocyte production, this may provide a rationale for boosting high-density lipoprotein levels after a myocardial infarction to prevent reocclusion.

Deep learning algorithms can be used to design systems that report data on patients and deliver warnings to medical applications or electronic health information if there are changes in the patient's health. These systems could be created using deep Learning. This helps verify that patients get the proper effective care at the proper time for each specific patient. A healthcare decision support system was presented using the Internet of Things and deep learning methods. In the proposed system, we examined the capability of integrating deep learning technology into automatic diagnosis and IoT capabilities for faster message exchange over the Internet. We have selected the suitable Neural Network structure (number of best-hidden layers and activation function classes) to construct the e-health system. In addition, the e-health system relied on data from doctors to understand the Neural Network. In the validation method, the total evaluation of the proposed healthcare system for diagnostics provides dependability under various patient conditions. Based on evaluation and simulation findings, a dual hidden layer of feed-forward NN and its neurons store the tanh function more effectively than other NN. To overcome challenges, this study will integrate artificial intelligence with IoT. This study aims to determine the NN's optimal layer counts and activation function variations.

Impact of the Use of Bendamustine Immediately before the Collection of Hematopoietic Stem Cells in Lymphoma. a Study By the Geltamo Group

Sickle cell disease is characterized by chronic anemia and vaso-occlusive crises, which eventually lead to multi-organ damage and premature death. Hematopoietic stem cell transplantation is the only curative treatment but it is limited by toxicity and poor availability of HLA-compatible donors. A gene therapy approach based on the autologous transplantation of lentiviral-corrected hematopoietic stem and progenitor cells was shown to be efficacious in one patient. However, alterations of the bone marrow environment and properties of the red blood cells hamper the harvesting and immunoselection of patients’ stem cells from bone marrow. The use of Filgrastim to mobilize large numbers of hematopoietic stem and progenitor cells into the circulation has been associated with severe adverse events in sickle cell patients. Thus, broader application of the gene therapy approach requires the development of alternative mobilization methods. We set up a phase I/II clinical trial whose primary objective was to assess the safety of a single injection of Plerixafor in sickle cell patients undergoing red blood cell exchange to decrease the hemoglobin S level to below 30%. The secondary objective was to measure the efficiency of mobilization and isolation of hematopoietic stem and progenitor cells. No adverse events were observed. Large numbers of CD34+ cells were mobilized extremely quickly. Importantly, the mobilized cells contained high numbers of hematopoietic stem cells, expressed high levels of stemness genes, and engrafted very efficiently in immunodeficient mice. Thus, Plerixafor can be safely used to mobilize hematopoietic stem cells in sickle cell patients; this finding opens up new avenues for treatment approaches based on gene addition and genome editing. Clinicaltrials.gov identifier: NCT02212535.

ALL Cells Mobilized by AMD3100 Are More Proliferative, and Remain In the Circulation Longer Than Normal HSC, Enhancing the Action of Vincristine

Safety and Risk of Allogeneic Peripheral Blood Stem Cell Donation: The Comprehensive Report of Nation-Wide Consecutively Pre-Registered 3,264 Family Donor Survey In 10years Project by Japan Society for Hematopoietic Cell Transplantation.

Timing of Daratumumab Administered Pre-Mobilization in Multiple Myeloma Impacts Pre-Harvest Peripheral Blood CD34+ Cell Counts and Plerixafor Use

Mobilization of Blood Stem Cells with G-CSF in Systemic Light-Chain Amyloidosis: Dominant Organ Involvement Significantly Affects Stem Cell Collection.