JP-2020527710-A5 -

Dates

Publication Date

20221215

Application Date

20180716

Description

As will be understood by those skilled in the art, such assessments are not typically intended to be accurate for 100% of the subjects being diagnosed. However, the term requires that the assessment be accurate for a statistically significant proportion of subjects (e.g., a cohort in a cohort study) . Whether the proportion is statistically significant can be determined without difficulty by those skilled in the art using various well-known statistical assessment tools, such as determining confidence intervals, p-values, Student's t-test, and Mann-Whitney test. Further details can be found in Dowdy and Wearden, Statistics for Research, John Wiley & Sons, New York 1983. Preferred confidence intervals are at least 90%, at least 95%, at least 97%, at least 98%, or at least 99%. Preferred p-values are 0.1, 0.05, 0.01, 0.005, or 0.0001. As used herein, the term "cardiovascular regeneration" includes the regeneration and/ or treatment and/or improvement of diseases related to the cardiovascular system . In another preferred embodiment, the method is used for preoperative prediction of the induction of angiogenic responses and /or responses to tissue repair in cardiovascular diseases such as myocardial infarction, stroke, and peripheral ischemic vascular disease, cardiac diseases, and/or ischemic preconditioning. Such treatments may include treatments using cardiovascular implants or stents, ventricular assist devices (VADs), pacemakers, and/or occluders or appropriate closure devices. Such treatments may also include treatments for diabetes, neoplastic diseases, gluten intolerance, rheumatic diseases, infections, sepsis, and/or hypertension. In particular, the method is used for preoperative prediction of improvement in left ventricular function, for example, after a decrease in left ventricular drive factor (LVEF) following acute ST-elevation myocardial infarction (STEM) and triple coronary artery disease, which are sequentially treated by acute percutaneous coronary intervention (PCI) and secondary coronary artery bypass grafting (CABG) revascularization. In yet another preferred embodiment, a method for predicting cardiac regeneration, particularly the induction of a stem cell therapy and /or angiogenic response and/or a response to tissue repair, under the circumstances of cardiovascular disease, uses a sample taken from a subject suffering from cardiac disease and/or arteriosclerosis. Such a sample may be taken from a subject suffering from angina pectoris, acute myocardial injury, cell necrosis, myocardial hypertrophy, heart failure, preferably ischemic heart failure, non-ischemic heart failure, myocarditis, atrial fibrillation, ventricular fibrillation and/or arteriosclerosis. Further embodiments of the beneficial method include the use of clinical diagnostic parameters. In particular, such parameters are selected from colony-forming unit (CFU) Hill assay, Matrigel Plug assay, body weight and/or left ventricular end-systolic volume (LVESV). Biomarker pre-identification: Distinct hematopoietic and endothelial CD133 + EPC subpopulations and angiogenic potential were tested in a cohort of 39 patients in bone marrow (BM) and peripheral blood (PB) using four-laser flow cytometry (LSR II, Becton Deckinson, Heidelberg, Germany) for co-expression analysis against in vitro CFU-EC, CFU-Hill, and in vivo Matrigel plug assays, as well as co-staining of a panel list of EPCs (co-staining panels CD133, 34, 117, 184, 309, 105, 45) and circulating endothelial cells (CECs) (co-staining panel: CD31, 146, 34, 45, 105, 184, 309). NT-proBNP and viral analyses were performed for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and parvovirus by IgG and antigen analysis in peripheral blood serum. Post-hoc analyses were performed for serum angiogenic factors and cytokines before final data closure. Post-hoc analysis: BM subpopulation analysis and SH2B3 mRNA RT-PCR in peripheral blood (PB): Methods and analysis of biomarkers studied in BM CD133 + and PBMNC samples were performed using cytometry bead array (CBA), enzyme-linked immunosorbent assay (ELISA), and RT-PCR.