bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/396101

Regeneration-Associated Cells Improve Recovery from Myocardial Infarction through Enhanced Vasculogenesis, Anti-inflammation, and Cardiomyogenesis

Salybekov, A. A.·Kawaguchi, A. T.·Masuda, H.·Vorateera, K.·Okada, C.·Asahara, T.
View original source ↗Export metadata ↓

Abstract

BackgroundConsidering the impaired function of regenerative cells in patients with comorbidities and associated risk factors, cell therapy to enhance the regenerative microenvironment was designed using regeneration-associated cells (RACs), including endothelial progenitor cells (EPCs) and anti-inflammatory cells.\n\nMethodsRACs were prepared by quality and quantity control culture of blood mononuclear cells (QQMNCs). The peripheral blood mononuclear cells (PBMNCs) were isolated from Lewis rats and conditioned for 5 days using a medium containing stem cell factors, thrombopoietin, Flt-3 ligand, vascular endothelial growth factor, and interleukin-6 to generate QQMNCs.\n\nResultsIn vitro EPC colony forming assays demonstrated a 5.3-fold increase in the definitive colony-forming EPCs and vasculogenic EPCs, in comparison to naive PBMNCs. Flow cytometry analysis revealed that QQMNCs were enriched with RACs, such as EPCs (28.9-fold, P<0.0019) and M2 macrophages (160.3-fold, P<0.0002). Cell transcriptome analysis revealed that angiogenesis (angpt1, angpt2, and vegfb), stem/progenitor (c-kit and sca-1) and anti-inflammation related (arg-1, erg-2, tgfb, and foxp3) genes were highly expressed in QQMNCs. For in vivo cell transplantation experiments, 1x105 cells were administered via the tail vein into syngeneic rat models of myocardial infarction (MI). Echocardiographic data showed that QQMNCs-transplanted group (QQ-Tx) preserved cardiac function and fraction shortening (45.5{+/-}4.6%) at 28-days post-MI in comparison with PBMNCs-transplanted (PB-Tx) (30.9{+/-}6.4%, P<0.0001) and Control (32.2{+/-}7.7%, P<0.0008) groups. Histological analysis revealed that QQ-Tx showed enhanced angiogenesis and reduced interstitial left ventricular fibrosis, along with a decrease in neutrophils and an increase in M2 macrophages in the acute phase of MI. Cell tracing studies revealed that intravenously administered QQMNCs preferentially homed to ischemic tissues via blood circulation, while PBMNCs did not. QQ-Tx showed markedly upregulated early cardiac transcriptional cofactors (Nkx2-5, 29.8-fold, and Gata-4, 5.2- fold) as well as c-kit (4.5-fold) while these markers were downregulated in PB-Tx. In QQ-Tx animals, de novo blood vessels formed a \"Biological Bypass\" as observed macroscopically and microscopically, while PB-Tx and Control-Tx groups never developed epicardial blood vessels but showed severe fibrotic adhesion to the surrounding tissues.\n\nConclusionQQMNCs, as RACs derived from rat PBMNCs, conferred potent angiogenic and anti-inflammatory properties to the regenerative microenvironment, enhancing myocardiogenesis and functional recovery of rat MI hearts.

Source connections

Explore related subjects

systems biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Salybekov, A. A., Kawaguchi, A. T., Masuda, H., Vorateera, K., Okada, C., Asahara, T.. 2018-08-20. Regeneration-Associated Cells Improve Recovery from Myocardial Infarction through Enhanced Vasculogenesis, Anti-inflammation, and Cardiomyogenesis. https://doi.org/10.1101/396101

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Uncovering disease progression trajectories across multiple timescales with hybrid ODE-mixture models

Biological systems are capable of evolving across multiple timescales, yet most modeling approaches capture either short-term physiological responses or long-term disease progression. Additionally, methods that combine these time scales either struggle with inter-individual variation, or require large volumes of data to work. We present Latent Class Parameter Trajectory Analysis (LCPTA), a hybrid framework that combines mechanistic ordinary differential equation (ODE) modeling of short-term dynamics with latent class trajectory modeling of long-term parameter evolution. To support this approach, we developed TemporalMixtureModels.jl, a Julia package for univariate and multivariate temporal mixture modeling. We evaluated LCPTA in two synthetic longitudinal studies, covering a simulation of a heterogeneous population developing hypertension, as well as a synthetic longitudinal study of 75 virtual individuals followed over 30 years, representing muscle insulin resistance, liver insulin resistance, and healthy trajectories. We compared LCPTA with a conditional neural ODE and a conditional neural network for reconstruction of long-term parameter trajectories and subgroup separation. In both studies LCPTA recovered relevant subgroup structure and trajectory patterns. In the cardiovascular study, the neural approaches were able to distinguish inter-individual differences, but in the insulin sensitivity study, neural approaches failed to represent parameter trajectories faithfully, primarily separating individuals along a single dominant parameter and showing weaker multivariate trajectory reconstruction. In additional experiments with sparse and irregularly sampled unseen individuals, LCPTA maintained strong classification performance. We show that LCPTA is an efficient and interpretable strategy for multiscale modeling of heterogeneous metabolic disease progression, with potential utility for data-efficient digital twin applications.

systems biology↗
bioRxiv2026

The Global Phosphorylation Landscape of Acute Heat Stress in Reef-Building Corals

Warming oceans disrupt the coral-algal symbiosis that sustains reefs, yet the signaling mechanisms initiating bleaching remain poorly understood. Integrating global phosphoproteomics across three reef-building corals with protein structure modeling revealed conservation between coral and human kinases, enabling inference of coral kinase activities and uncovering a shared signaling program induced by acute heat stress. Heat rapidly activated ERK, JNK, and p38 MAP kinases, suppressed cell cycle signaling, and remodeled pathways controlling chromatin, RNA processing, and metabolism. Most strikingly, thermal stress rewired immune receptor signaling networks associated with non-self recognition, suggesting that heat shifts the coral host from tolerance to immune recognition of its algal symbionts. These findings define conserved signaling mechanisms that precede bleaching, revealing actionable molecular targets for enhancing coral resilience.

systems biology↗
bioRxiv2026

Estimating glioblastoma migration-to-proliferation ratio from single time-point MRI data via radial density distribution

Glioblastoma (GBM) tumors with a high migration-to-proliferation ratio (D/k) are associated with treatment resistance, motivating the estimation of D/k from routine pre-treatment magnetic resonance imaging (MRI) data and the investigation of mechanisms underlying its heterogeneity across patients. Unlike previous approaches based on nested spherical approximations of enhancing and non-enhancing tumor volumes, we incorporate the spatial arrangement of the enhancing and non-enhancing tumor regions by deriving a 1D tumor density distribution from their segmentations and fitting a 1D reaction-diffusion model to estimate D/k. We achieved an error of under 5% when comparing our method to synthetic density distributions and found excellent correlation with synthetic tumor segmentations (Pearson correlation coefficient (PCC) = 0.996). We then evaluated associations between patient-specific D/k values and their clinical, transcriptomic, and radiomic features. When applied to 102 pre-treatment MRI scans from the Brain Tumor Segmentation (BraTS) 2017 dataset, elevated D/k significantly correlated with reduced overall survival (log-rank p = 0.01), older age (p = 0.04), and a trend toward lower Karnofsky Performance Status (p = 0.059). In a subset of 91 patients with available microarray data, mesenchymal-like phenotypes consistently exhibited elevated D/k across three established molecular subtype classifications (p = 0.013, p = 0.055, and p = 0.127). Elastic Net regularization followed by overrepresentation analysis revealed an enrichment of glycosylation-related pathways among genes associated with D/k variability (p = 0.0123 and p = 0.0368). Furthermore, Multi-Omic Factor Analysis identified a radiomic factor correlated with D/k (r = 0.57, p = 4x10-9), with the highest-weighted features corresponding to smoothness of the non-enhancing tumor region on T2 and FLAIR.

systems biology↗