RESUMEN
The derivation of mesenchymal progenitors from human embryonic stem cells (hESCs) has recently been reported. We studied the immune characteristics of these hESC-derived mesenchymal progenitors (EMPs) and their interactions with T lymphocytes and natural killer cells (NKs), two populations of lymphocytes with important roles in transplantation immunology. EMPs express a number of bone marrow mesenchymal stromal cell (BMMSC) markers, as well as the hESC marker SSEA-4. Immunologically, EMPs do not express HLA-DR or costimulatory molecules. On the other hand, HLA-G, a nonclassic MHC I protein involved in mediating maternal-fetal tolerance, can be found on the surface of EMPs, and its expression is increased after interferon-gamma stimulation. EMPs can suppress CD4(+) or CD8(+) lymphocyte proliferation, similar to BMMSCs. However, EMPs are more resistant to NK-mediated lysis than BMMSCs and can suppress the cytotoxic effects of activated NKs, as well as downregulating the NK-activating receptors NKp30 and NKp46. With their broad immunosuppressive properties, EMPs may represent a new potential cell source for therapeutic use.
Asunto(s)
Células Madre Embrionarias/citología , Células Asesinas Naturales/inmunología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/patología , Linfocitos T/inmunología , Apoptosis/efectos de los fármacos , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Antígeno CD56/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Línea Celular , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Humanos , Inmunofenotipificación , Interferón gamma/farmacología , Interleucina-15/farmacología , Interleucina-2/farmacología , Linfocitos T/citologíaRESUMEN
BACKGROUND AND PURPOSE: Poorly controlled blood glucose was reported to cause deterioration of acute ischemic stroke. In this study, we investigated whether an elevated admission serum glucose level in the 3-h time window of intravenous thrombolysis for acute ischemic stroke determined poor functional outcomes among Chinese population. METHODS: This was a prospective cohort study. From December 1, 2004 to December 31, 2016, a total of 2370 patients were enrolled and categorized into two cohorts by blood glucose levels of ≥200 and <200â¯mg/dl in the 3â¯h after stroke onset. The primary objective was to determine whether admission hyperglycemia increased major disability and death at 30 and 90â¯days, which was defined by a modified Rankin Scale of 3-6. The secondary objective was to determine whether admission hyperglycemia increased the symptomatic intracranial hemorrhage (SICH) at 90â¯days. The number needed to harm (NNH) and patient expected event rate (PEER) were evaluated for both the primary and secondary objectives. RESULTS: The primary outcome occurred in 216 of 305 patients (70.8%) in the blood glucose ≥200â¯mg/dl cohort and in 951 of 1587 patients (59.9%) in the blood glucose <200â¯mg/dl cohort at 30â¯days, and in 191 of 287 patients (66.6%) in the blood glucose ≥200â¯mg/dl cohort and in 827 of 1517 patients (54.5%) in the blood glucose <200â¯mg/dl cohort at 90â¯days. Patients with admission hyperglycemia had significantly increased major disability and death at 30 (adjusted relative risk (RR): 1.194 [1.073-1.329], pâ¯=â¯0.0012) and 90â¯days (adjusted RR: 1.203 [1.079-1.340], pâ¯=â¯0.0008). Admission hyperglycemia increased the risk of the occurrence of SICH by nearly 2-fold (adjusted RR: 1.891 [0.977-3.657], pâ¯=â¯0.0585 with the SITS-MOST criteria and adjusted RR: 1.884 [1.138-3.121], pâ¯=â¯0.0139 with the NINDS criteria). NNH values of admission hyperglycemia in major disability and death at 30 and 90â¯days were 9 and 10, and NNH values of SICH by the SITS-MOST NINDS criteria were 44 and 34, respectively. CONCLUSIONS: The study evidenced the association and temporal relationship of admission hyperglycemia causing deterioration of functional outcomes and increased SICH among Chinese population with acute ischemic stroke treated with intravenous thrombolysis.
Asunto(s)
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Hiperglucemia/diagnóstico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Administración Intravenosa , Anciano , Biomarcadores/sangre , Glucemia , Isquemia Encefálica/epidemiología , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Hiperglucemia/epidemiología , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.