Evidence map›Paper›PMID 41692780›Full record

ReviewStem cell research & therapy2026

Research progress on the effects of M1/M2 macrophages on the differentiation and maturation of stem cell-derived cardiomyocytes: a review.

Xi Wu, Fan Zhou, Junsheng Mu

Abstract readReview
In one paragraph

Review in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Xi WuDepartment of Cardiac Surgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, China.
Fan ZhouDepartment of Ultrasound, The Third Medical Center of People's Liberation Army of China General Hospital, Beijing, 100039, China. zhoufan29@sina.com.
Junsheng MuDepartment of Cardiac Surgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453000, Henan, China. wesleymu@Hotmail.com.

Funding

National natural science foundation 82270255
6 · The paper itself

Abstract

Stem cell-derived cardiomyocytes (SC-CMs) represent a promising cell source for cardiac regenerative medicine, disease modeling, and drug screening. However, their clinical translation faces significant challenges, including functional immaturity, poor long-term survival, and inadequate integration with host tissue following transplantation. The immune microenvironment, particularly the dynamic polarization of macrophages into pro-inflammatory (M1) or reparative (M2) phenotypes, is increasingly recognized as a critical regulator of cardiac repair, yet a systematic understanding of its specific effects on SC-CM fate remains incomplete. This review aims to comprehensively evaluate the dual regulatory roles of M1 and M2 macrophages on the differentiation efficiency, structural and functional maturation, and in vivo transplantation efficacy of SC-CMs. A systematic literature search was conducted in PubMed, Web of Science, Nature, and CNKI for relevant studies published from database inception to July 2025. After screening, 92 articles were included for analysis. The synthesized evidence demonstrates that M1 macrophages and their secreted factors (e.g., TNF-α, IL-1β) impede cardiac differentiation by inhibiting the Wnt/β-catenin pathway, disrupt sarcomeric organization and calcium handling, and maintain SC-CMs in a glycolytic, immature state. In contrast, M2 macrophages enhance SC-CM maturation by providing trophic support (e.g., IGF-1, HGF), promoting electrophysiological maturation and metabolic reprogramming towards oxidative phosphorylation, and facilitating angiogenesis via VEGF. The novelty of this review lies in its integrated perspective on macrophage-driven immunomodulation as a central axis for SC-CM maturation. Furthermore, it discusses emerging therapeutic strategies—such as optimized transplantation timing, co-transplantation with immunomodulatory cells, engineered exosomes, and smart biomaterials—that leverage macrophage polarization to create a favorable microenvironment for SC-CMs. Ultimately, harnessing macrophage-SC-CM crosstalk is a crucial step toward advancing clinically effective and immunologically informed cardiac regeneration therapies.

Indexed as

Cell DifferentiationMacrophagesMyocytes, CardiacAnimalsHumansImmune microenvironmentMacrophage polarizationMaturationStem cell-derived cardiomyocytesTissue regeneration

Identifiers

PMID41692780
PMCPMC13011457

What OpenQuestion 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 OpenQuestion graph.