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August 28, 2026Nature CommunicationsOpen Access

Transplanting bone marrow MSCs from HF mice drives inflammatory macrophage accumulation and worsens cardiac remodeling.

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Why the study?

Heart failure induces innate immune memory in hematopoietic stem and progenitor cells, but the role of the bone marrow microenvironment in this memory remains poorly understood.

Population

Mice with heart failure and human bone marrow

Design

Preclinical experimental study

Key result

Transplanting bone marrow mesenchymal stromal cells from mice with heart failure caused inflammatory macrophages to accumulate in the heart and worsened cardiac remodeling.

Authors

KGKohsaku GotoYNYukiteru NakayamaJSJunichi Sugita

Discussion

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Key expert perspectives

Captured external expert commentary on this paper, strongest first. Original sources are linked where available.

DHDr. Hideki KatagiriProject Manager

“This project has made the early detection of heart failure, a complication of diabetes, and its prevention and treatment a major pillar of its work. This achievement develops the same group's original discovery that the occurrence of heart failure is memorized by bone marrow cells and is related to its recurrence and multiple diseases, and advances the elucidation of the mechanism, including the molecular mechanism and the cell types involved. By elucidating the target cells and molecules, it is believed that this will form the basis of a strategy for the prevention and treatment of heart failure and related multiple diseases, which is revolutionary and considered to be a very significant achievement for this project.”

Japan Science and Technology Agency (JST) Moonshot Research and Development Program

Overview

Leptin receptor+ stromal cells may mediate HF immune memory; hypothesis-generating for niche-targeted interventions, no clinical implications yet.

Key Points

  • To determine how the bone marrow microenvironment and stromal cells regulate innate immune memory in hematopoietic progenitors during heart failure.
  • Transplanted leptin receptor-positive bone marrow mesenchymal stromal cells from mice with heart failure alongside healthy hematopoietic stem and progenitor cells.
  • Assessed growth factor signaling, stromal subpopulation dynamics, and macrophage accumulation in mouse cardiac tissue.
  • Analyzed human bone marrow samples to evaluate corresponding stromal subpopulations and marrow adiposity during heart failure.
  • Transplantation of heart failure-primed stromal cells led to cardiac accumulation of inflammatory macrophages and worsened adverse cardiac remodeling.
  • Heart failure depleted a stromal subpopulation producing heparin-binding epidermal growth factor, suppressed hematopoietic growth factor signaling, and activated a fat-forming stromal program.
  • Identified an equivalent stromal subpopulation and demonstrated increased bone marrow fat in humans with heart failure.

Structured PICO

P
Population
Male LEPR-tdTomato mice (generated by crossing Lepr-cre mice with reporter mice) subjected to transverse aortic constriction (TAC) to induce heart failure or sham operation, and irradiated male recipient mice.
I
Intervention
Co-transplantation of bone marrow mesenchymal stromal cells (MSCs) from mice with heart failure (T-MSCs) together with healthy hematopoietic stem and progenitor cells (HSPCs).
C
Comparator
Co-transplantation of bone marrow mesenchymal stromal cells (MSCs) from sham-operated control mice (C-MSCs) together with healthy hematopoietic stem and progenitor cells (HSPCs).
O
Outcome
Cardiac contractile function, chamber dilation, and cardiac fibrosis at 6 months after co-transplantation.surrogate

Heart failure induces innate immune memory in bone marrow mesenchymal stromal cells, which subsequently alters hematopoietic stem cells to promote pro-inflammatory macrophage accumulation and worsen cardiac dysfunction.

Cite This Study

Goto et al. (2026) studied Heart failure. Transplanting bone marrow mesenchymal stromal cells from mice with heart failure was evaluated on Inflammatory macrophage accumulation and cardiac remodeling. Transplanting bone marrow mesenchymal stromal cells from mice with heart failure caused inflammatory macrophages to accumulate in the heart and worsened cardiac remodeling.

synapsesocial.com/papers/6a9145ead15324a1df3a92f4https://doi.org/10.1038/s41467-026-76178-z
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Heart failure promotes multimorbidity through innate immune memory2024 · 41 citations
  2. 2Heart Failure Impairs Bone Marrow Hematopoietic Stem Cell Function and Responses to Injury2023 · 12 citations
  3. 3Transcriptional changes in bone marrow stromal cells of patients with heart failure2014 · 3 citations
  4. 4Distinct Cardiometabolic Stressors Differentially Regulate Bone Marrow Myeloid Progenitors2026
  5. 5Myeloid Fatty Acid Metabolism Activates Neighboring Hematopoietic Stem Cells to Promote Heart Failure With Preserved Ejection Fraction2025 · 19 citations