Cardiogenic Shock Classification and Associated Mortality Risk.

The Society for Cardiovascular Angiography and Interventions (SCAI) Shock Classification was developed to create standardized language describing the severity of cardiogenic shock (CS). The purposes of this review were to evaluate short-term and long-term mortality rates at each SCAI shock stage for patients with or at risk for CS, which has not been studied previously, and to propose using the SCAI Shock Classification to develop algorithms for clinical status monitoring. A detailed literature search was conducted for articles published from 2019 through 2022 in which the SCAI shock stages were used to assess the mortality risk. In total, 30 articles were reviewed. The SCAI Shock Classification at hospital admission revealed a consistent and reproducible graded association between shock severity and mortality risk. Furthermore, shock severity correlated incrementally with mortality risk even after patients were stratified for diagnosis, treatment modalities, risk modifiers, shock phenotype, and underlying cause. The SCAI Shock Classification system can be used to evaluate mortality across populations of patients with or at risk for CS including those with different causes, shock phenotypes, and comorbid conditions. We propose an algorithm that uses clinical parameters incorporating the SCAI Shock Classification into the electronic health record to continually reassess and reclassify the presence and severity of CS across time throughout hospitalization. The algorithm has the potential to alert the care team and a CS team, leading to earlier recognition and stabilization of the patient, and may facilitate the use of treatment algorithms and prevent CS deterioration, leading to improved outcomes.

A fibrin patch-based enhanced delivery of human embryonic stem cell-derived vascular cell transplantation in a porcine model of postinfarction left ventricular remodeling.

It is unknown how to use human embryonic stem cell (hESC) to effectively treat hearts with postinfarction left ventricular (LV) remodeling. Using a porcine model of postinfarction LV remodeling, this study examined the functional improvement of enhanced delivery of combined transplantation of hESC-derived endothelial cells (ECs) and hESC-derived smooth muscle cells (SMCs) with a fibrin three-dimensional (3D) porous scaffold biomatrix. To facilitate tracking the transplanted cells, the hESCs were genetically modified to stably express green fluorescent protein and luciferase (GFP/Luc). Myocardial infarction (MI) was created by ligating the first diagonal coronary artery for 60 minutes followed by reperfusion. Two million each of GFP/Luc hESC-derived ECs and SMCs were seeded in the 3D porous biomatrix patch and applied to the region of ischemia/reperfusion for cell group (MI+P+C, n = 6), whereas biomatrix without cell (MI+P, n = 5), or saline only (MI, n = 5) were applied to control group hearts with same coronary artery ligation. Functional outcome (1 and 4 weeks follow-up) of stem cell transplantation was assessed by cardiac magnetic resonance imaging. The transplantation of hESC-derived vascular cells resulted in significant LV functional improvement. Significant engraftment of hESC-derived cells was confirmed by both in vivo and ex vivo bioluminescent imaging. The mechanism underlying the functional beneficial effects of cardiac progenitor transplantation is attributed to the increased neovascularization. These findings demonstrate a promising therapeutic potential of using these hESC-derived vascular cell types and the mode of patch delivery.

Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells.

Mesenchymal stem/stromal cells (MSCs) have been isolated from various tissues and utilized for an expanding number of therapies. The developmental pathways involved in producing MSCs and the phenotypic precursor/progenitor cells that give rise to human MSCs remain poorly defined. Human embryonic stem cells (hESCs) have the capability to generate functional hemato-endothelial cells and other mesoderm lineage cells. hESC-derived CD73(+) cells have been isolated and found to have similar phenotypic and functional characteristics as adult MSCs. Here we demonstrate hESC-derived CD34(+)CD73(-) cells can serve as MSC progenitor cells with the ability to differentiate into adipocytes, osteoblasts and chondrocytes. Additionally, gene array analysis of hESC-derived MSCs show substantially different gene expression compared to bone marrow (BM)-derived MSCs, especially with increased expression of pluripotent and multipotent stem cell and endothelial cell-associated genes. The isolation of functional MSCs from hESC-derived CD34(+)CD73(-) cells provides improved understanding of MSC development and utilization of pluripotent stem cells to produce MSCs suited for novel regenerative therapies.

Human embryonic stem cell-derived vascular progenitor cells capable of endothelial and smooth muscle cell function.

OBJECTIVE: Previous studies have demonstrated development of endothelial cells (ECs) and smooth muscle cells (SMCs) as separate cell lineages derived from human embryonic stem cells (hESCs). We demonstrate CD34(+) cells isolated from differentiated hESCs function as vascular progenitor cells capable of producing both ECs and SMCs. These studies better define the developmental origin and reveal the relationship between these two cell types, as well as provide a more complete biological characterization. MATERIALS AND METHODS: hESCs are cocultured on M2-10B4 stromal cells or Wnt1-expressing M2-10B4 for 13 to 15 days to generate a CD34(+) cell population. These cells are isolated using a magnetic antibody separation kit and cultured on fibronectin-coated dishes in EC medium. To induce SMC differentiation, culture medium is changed and a morphological and phenotypic change occurs within 24 to 48 hours. RESULTS: CD34(+) vascular progenitor cells give rise to ECs and SMCs. The two populations express respective cell-specific transcripts and proteins, exhibit intracellular calcium in response to various agonists, and form robust tube-like structures when cocultured in Matrigel. Human umbilical vein endothelial cells cultured under SMC conditions do not exhibit a change in phenotype or genotype. Wnt1-overexpressing stromal cells produced an increased number of progenitor cells. CONCLUSIONS: The ability to generate large numbers of ECs and SMCs from a single vascular progenitor cell population is promising for therapeutic use to treat a variety of diseased and ischemic conditions. The stepwise differentiation outlined here is an efficient, reproducible method with potential for large-scale cultures suitable for clinical applications.

Hematopoietic differentiation of human embryonic stem cells by cocultivation with stromal layers.

Human embryonic stem (hES) cells are of remarkable interest both for the utility of these cells for studying basic human developmental biology and as a potential source for novel therapeutics. Here, we provide detailed methodologies of one of the first systems used to mediate differentiation of hES cells--stromal cell coculture. Use of stromal cells adds the ability to manipulate aspects of the developmental niche that support differentiation into a defined lineage. These methods will allow efficient and reproducible development of hematopoietic progenitor cells, as well as potentially mature hematopoietic cells that are suitable for subsequent in vitro and in vivo studies.