Stem cell‐based therapies for cardiac diseases: The critical role of angiogenic exosomes

BioFactors ◽  
2021 ◽  
Author(s):  
Sara Ghodrat ◽  
Seyed Javad Hoseini ◽  
Shiva Asadpour ◽  
Simin Nazarnezhad ◽  
Fariba Alizadeh Eghtedar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Critical Role ◽  
Cardiac Diseases

scholarly journals Role of HLA in Hematopoietic Stem Cell Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Meerim Park ◽  
Jong Jin Seo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Critical Role ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hematopoietic Stem

The selection of hematopoietic stem cell transplantation (HSCT) donors includes a rigorous assessment of the availability and human leukocyte antigen (HLA) match status of donors. HLA plays a critical role in HSCT, but its involvement in HSCT is constantly in flux because of changing technologies and variations in clinical transplantation results. The increased availability of HSCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of killer-cell immunoglobulin-like receptor (KIR) genes in HSCT. The influence of nongenetic factors on the tolerability of HLA mismatching has recently become evident, demonstrating a need for the integration of both genetic and nongenetic variables in donor selection.

Abstract 13: Plasminogen Is Required for Hematopoietic Stem Cell-Mediated Cardiac Repair After Myocardial Infarction

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Yanqing Gong ◽  
Jane Hoover-Plow ◽  
Ying Li
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Tissue Repair ◽  
Critical Role ◽  
Cardiac Repair ◽  
Internal Diameter ◽  
Hematopoietic Stem

Ischemic heart disease, including myocardial infarction (MI), is the primary cause of death throughout the US. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize hematopoietic progenitor and stem cells (HPSC) to improve cardiac recovery after MI. However, poor-mobilization to G-CSF is observed in 25% of patients and 10-20% of healthy donors. Therefore, a better understanding of the underlying mechanisms regulating G-CSF-induced cardiac repair may offer novel approaches for strengthening stem cell-mediated therapeutics. Our previous studies have identified an essential role of Plg in HPSC mobilization from bone marrow (BM) in response to G-CSF. Here, we investigate the role of Plg in G-CSF-stimulated cardiac repair after MI. Our data show that G-CSF significantly improves cardiac tissue repair including increasing neovascularization in the infarct area, and improving ejection fraction and LV internal diameter by echocardiogram in wild-type mice. No improvement in tissue repair and heart function by G-CSF is observed in Plg -/- mice, indicating that Plg is required for G-CSF-regulated cardiac repair after MI. To investigate whether Plg regulates HPSC recruitment to ischemia area, bone marrow transplantion (BMT) with EGFP-expressing BM cells was performed to visualize BM-derived stem cells in infarcted tissue. Our data show that G-CSF dramatically increases recruitment of GFP+ cells (by 16 fold) in WT mice but not in Plg -/- mice, suggesting that Plg is essential for HPSC recruitment from BM to the lesion sites after MI. In further studies, we investigated the role of Plg in the regulation of SDF-1/CXCR-4 axis, a major regulator for HPSC recruitment. Our results show that G-CSF significantly increases CXCR-4 expression in infarcted area in WT mice. While G-CSF-induced CXCR-4 expression is markedly decreased (80%) in Plg -/- mice, suggesting Plg may regulate CXCR-4 expression during HSPC recruitment to injured heart. Interestingly, Plg does not affect SDF-1 expression in response to G-CSF treatment. Taken together, our findings have identified a critical role of Plg in HSPC recruitment to the lesion site and subsequent tissue repair after MI. Thus, targeting Plg may offer a new therapeutic strategy to improve G-CSF-mediated cardiac repair after MI.

Role of Histopathology in Management of Graft Versus Host Disease (GVHD). A Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4647-4647
Author(s):  
Irene Maria Cavattoni ◽  
Enrico Morello ◽  
Norbert Pescosta ◽  
Marco Casini ◽  
Giovanni Negri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Data ◽  
Predictive Value ◽  
Screening Test ◽  
Chronic Gvhd ◽  
Critical Role ◽  
Histopathological Diagnosis ◽  
Gi Tract ◽  
Asymptomatic Patients

Abstract Abstract 4647 Background and Aims GVHD is a major complication after allogeneic stem cell transplantation (HSCT). The median incidence of grade II-IV acute(a)GVHD is about 40%, depending on several risk factors, whereas chronic(c)GVHD occurs in more than 50% of long term survivors after HSCT.Histopathology has a critical role in obtaining diagnosis and comprehending pathophysiology of GVHD. However, clinical or technical factors may hamper histological interpretation. Aim of the present retrospective study was to optimize the role of histopathology in the management of GVHD. Recommendations of Pathology Working Group (National Institutes of Health Consensus, ASBMT, BBMT 2006) were matched with clinical-laboratory data in order to test histological sensitivity, specificity and positive predictive value (PPV). Patients and Methods One hundred sixty consecutive bioptical samples were performed in 68 adult patients with suggestive signs or symptoms of organ involving a/c GVHD (n=137) or as screening test in asymptomatic patients (n=23),who underwent allogeneic HSCT at our institution between Jul 1999 and Feb 2009.Median age at transplant was 50 ys (range 17-70),with a median follow-up 32 mo (3-111). Diagnoses were 89/160 acute and 16/160 chronic leukemia, 16 lymphomas, and 39 myelomas. Sixteen % of biopsies were taken from MUD transplanted patients. The source of stem cells was bone marrow in 88/160 (median TNC 2.9 × 108/Kg, range 1.11-5.60), and peripheral blood in 72 (median CD34+cells 5.87 × 106/Kg, range 1.17-10.15). The biopsies, were collected from organ presenting clinical signs suggestive of GVHD involvement. If more organs were simultaneously involved,the one with more severe symptoms was selected. The biopsies were performed early at the onset of the clinical manifestations, and before modification of immunosuppressive (IS) therapy. A specific form containing the main clinical data (time from transplant, type of conditioning and possible differential diagnosis) accompanied the specimens. The histopathological diagnosis was guaranteed within 24-48 hours from the collection. The 160 bioptical samples were collected from the skin (n=86), gastrointestinal tract (GI) (oral mucosa n=5, stomach n=40, or colon n=24), liver (n=4), lung (n=1).Median time from HSCT to biopsy was 968 days (range 76-3341).PPV for the following variables was calculated: conditioning therapy (reduced intensity versus standard), source of stem cell (BM versus PB),type of organ involved (skin, versus upper GI tract, versus lower GI tract), time from HSCT to biopsy (<=180 vs >180 dy) and concomitant IS at the time of biopsy. Results Seventy out of 157 biopsies were negative, 9/157 suggestive for GVHD, 48/157 were diagnostic for acute GVHD (33 had histological grade <= 2, 15 > 2), and 30/157 for chronic GVHD. The sensitivity of the histopathological test was 79% in the whole group, whereas the specificity was 80%. PPV was 86%, negative predictive value was 71%. About the analyzed variables,the following had a PPV >=90% :RIC conditioning (90%),PB source (93%),samples collected from GI tract (upper tract 90%, lower 100%),time to biopsy >180 dy(90%) and absence of concomitant IS treatment (90%).The biopsies performed as screening test in asymptomatic patients had a sensitivity of 100% but a specificity of 83%, and the true positive are as frequent as the false positive results. Conclusions: clinical data identified at the time of sampling (RIC conditioning, PBSC transplants, lower GI tract, time to biopsy >180 dy and absence of concomitant IS) may improve the power of histology. Moreover, despite of a low number of specimens, the biopsies performed as screening test seem to have no critical role in decision making. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications

2021 ◽  
Vol 22 (17) ◽  
pp. 9615
Author(s):  
Ji-Yoon Noh
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Transcription Factors ◽  
Blood Cells ◽  
Thrombus Formation ◽  
Critical Role ◽  
Clinical Implications ◽  
Disease Development ◽  
Hematopoietic Stem

Platelets play a critical role in hemostasis and thrombus formation. Platelets are small, anucleate, and short-lived blood cells that are produced by the large, polyploid, and hematopoietic stem cell (HSC)-derived megakaryocytes in bone marrow. Approximately 3000 platelets are released from one megakaryocyte, and thus, it is important to understand the physiologically relevant mechanism of development of mature megakaryocytes. Many genes, including several key transcription factors, have been shown to be crucial for platelet biogenesis. Mutations in these genes can perturb megakaryopoiesis or thrombopoiesis, resulting in thrombocytopenia. Metabolic changes owing to inflammation, ageing, or diseases such as cancer, in which platelets play crucial roles in disease development, can also affect platelet biogenesis. In this review, I describe the characteristics of platelets and megakaryocytes in terms of their differentiation processes. The role of several critical transcription factors have been discussed to better understand the changes in platelet biogenesis that occur during disease or ageing.

scholarly journals Investigating the role of super-enhancer RNAs underlying embryonic stem cell differentiation

BMC Genomics ◽  
2019 ◽  
Vol 20 (S10) ◽  
Author(s):  
Hao-Chun Chang ◽  
Hsuan-Cheng Huang ◽  
Hsueh-Fen Juan ◽  
Chia-Lang Hsu
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Heart Development ◽  
Critical Role ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Regulation Mechanism ◽  
Super Enhancer

Abstract Background Super-enhancer RNAs (seRNAs) are a kind of noncoding RNA transcribed from super-enhancer regions. The regulation mechanism and functional role of seRNAs are still unclear. Although super-enhancers play a critical role in the core transcriptional regulatory circuity of embryonic stem cell (ESC) differentiation, whether seRNAs have similar properties should be further investigated. Results We analyzed cap analysis gene expression sequencing (CAGE-seq) datasets collected during the differentiation of embryonic stem cells (ESCs) to cardiomyocytes to identify the seRNAs. A non-negative matrix factorization algorithm was applied to decompose the seRNA profiles and reveal two hidden stages during the ESC differentiation. We further identified 95 and 78 seRNAs associated with early- and late-stage ESC differentiation, respectively. We found that the binding sites of master regulators of ESC differentiation, including NANOG, FOXA2, and MYC, were significantly observed in the loci of the stage-specific seRNAs. Based on the investigation of genes coexpressed with seRNA, these stage-specific seRNAs might be involved in cardiac-related functions such as myofibril assembly and heart development and act in trans to regulate the co-expressed genes. Conclusions In this study, we used a computational approach to demonstrate the possible role of seRNAs during ESC differentiation.

scholarly journals Unveiling the critical role of REX1 in the regulation of human stem cell pluripotency

Stem Cells ◽  
2013 ◽  
Vol 31 (11) ◽  
pp. 2374-2387 ◽  
Author(s):  
Mi-Young Son ◽  
Hoonsung Choi ◽  
Yong-Mahn Han ◽  
Yee Sook Cho
Keyword(s):  
Stem Cell ◽  
Critical Role ◽  
Human Stem Cell ◽  
Stem Cell Pluripotency
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