PXD044560

PXD044560 is an original dataset announced via ProteomeXchange.

Title	LC-MS/MS of conditioned media from vascularized cardiac tissue with and without primitive macrophages
Description	Primitive macrophages enhance a perivascular niche to enable vascular perfusion in human cardiac tissue The intricate anatomical structure and high cellular density of the myocardium significantly complicate the bioengineering of vascular networks within cardiac tissues, creating challenges in establishing a perfusable and stable vasculature within these tissues. Emerging evidence from murine in vivo studies underscores the significant role of resident cardiac macrophages in facilitating cardiac regeneration post-injury, specifically their role in enhancing angiogenesis. Here, for the first time, we integrate human pluripotent stem cell derived macrophages, resembling primitive yolk-sac derived macrophages, within human in vitro vascularized heart-on-chip platforms. The incorporation of primitive macrophages had a profound impact on the long term functionality of microvascularized cardiac tissue, particularly in enabling formation of perfusable vasculature with a stable barrier function that persisted for two weeks in culture. These effects were contingent on physical cell-cell interactions and significantly diminished in transwell culture. The inclusion of primitive macrophages mitigated tissue cytotoxicity and curtailed the release of cell-free mitochondrial-DNA, underscoring their indispensable role for mitigating cell damage in bioengineered tissues. Furthermore, their incorporation upregulated the secretion of pro-angiogenic, matrix remodeling and cardioprotective cytokines such as MMP-12, MMP-2, Angiopoietin-like 1, NRG-3, SIGIRR and Adiponectin. RNA sequencing disclosed upregulation of cardiac maturation (TTNI3, SCN5A, MYL2, and RYR2), and endothelial cells genes (PDGF-B, PECAM-1 and CDH5) as well as enhancement of angiogenic signaling, Wnt and PDGF pathways. Collectively, our results offer valuable insights into the integral role of primitive macrophages in directing long-term functional vascularization of cardiac tissues, paving the way for novel therapeutic strategies and advancing heart-on-a-chip systems.
HostingRepository	PRIDE
AnnounceDate	2025-08-04
AnnouncementXML	Submission_2025-08-03_16:07:38.342.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Saikali
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-14 05:55:37	ID requested
⏵ 1	2025-08-03 16:07:39	announced

10.1016/j.stem.2024.05.011;

Landau S, Zhao Y, Hamidzada H, Kent GM, Okhovatian S, Lu RXZ, Liu C, Wagner KT, Cheung K, Shawky SA, Vosoughi D, Beroncal EL, Fernandes I, Cummins CL, Andreazza AC, Keller GM, Epelman S, Radisic M, Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms. Cell Stem Cell, 31(8):1222-1238.e10(2024) [pubmed]

submitter keyword: vascularization, cardiomyocyte,myocardium, resident macrophage, pluripotent stem cell, conditioned media

Carolyn L. Cummins
contact affiliation	Lelie Dan Faulty of Pharmacy, Univerity of Toronto
contact email	caroyn.cummins@utoronto.ca
lab head
Michael Saikali
contact affiliation	University of Toronto
contact email	michael.saikali@mail.utoronto.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD044560

PRIDE project URI

• PRIDE
  1. PXD044560
     1. Label: PRIDE project
     2. Name: LC-MS/MS of conditioned media from vascularized cardiac tissue with and without primitive macrophages