Evidence map›Paper›PMID 41369369›Full record

ArticleCells2025

A Macrophage-Derived Factor on Human iPSC-Derived Cardiomyocyte Function: The Role of Osteopontin.

Lei Hao, Eun Jung Lee

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Lei HaoDepartment of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Eun Jung LeeDepartment of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.ORCID 0000-0003-2257-9319

Funding

NIH HHS NIH R15 HL145726NSF NSF CAREER 1653464
6 · The paper itself

Abstract

Following MI, massive cardiomyocytes are lost, and inflammatory cells such as monocytes and macrophages migrate into the damaged region to remove dead cells and tissue. While cardiac macrophages are abundant in the injured heart post-MI, the role of inflammation in cardiovascular disease has been under-appreciated in the past. Consequently, the contribution of specific macrophage subsets or macrophage-derived factors on cardiac cells is not well known. Thus, this study investigated the paracrine signaling between human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and macrophages, with the focus on the effects of macrophage-derived osteopontin (OPN) on hiPSC-CM function. HiPSC-CM were first co-cultured with unpolarized (M0), pro-inflammatory (M1), or anti-inflammatory (M2) macrophages. The co-culture of hiPSC-CM with M2 macrophages specifically led to notable changes in the electrophysiological properties of hiPSC-CM, including prolonged contraction time (RT90), action potential duration (APD90), and calcium decay time (CSD RT90). Moreover, a significant upregulation of action potential-related genes such as CACNA1C and SCN5A was demonstrated, which coincided with the elevated OPN level in the hiPSC-CM with M2 macrophages co-culture. These functional changes were not observed in the hiPSC-CM-M0 and M1 co-culture groups, likely due to the OPN level remaining below the threshold required to induce detectable changes in hiPSC-CM. Subsequent experiments involving exogenous OPN supplementation and inhibition in hiPSC-CM culture yielded concordant results, further confirming the direct role of OPN in modulating hiPSC-CM gene expression. This study highlights the differential effect of specific macrophage subtypes on hiPSC-CM, as well as the potent bioactivity of OPN and its ability to directly modulate cardiomyocyte behavior, even in the absence of direct cell-cell interactions within a co-culture system. These findings further suggest that OPN could be a novel target for therapeutic intervention in cardiac diseases.

Indexed as

Induced Pluripotent Stem CellsMacrophagesMyocytes, CardiacOsteopontinAction PotentialsCell DifferentiationCoculture TechniquesHumansOsteopontincardiac remodelinghuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)inflammationmacrophagesmyocardial infarctionosteopontin

Identifiers

PMID41369369
PMCPMC12691140

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.