Related Experiment Video
Updated: Jul 18, 2025
Transplantation of Neonatal Mouse Cardiac Macrophages into Adult Mice
Published on: March 20, 2021
Targeted heart repair by Tβ4-loaded cardiac-resident macrophage-derived extracellular vesicles modified with monocyte
Peier Chen1, Yuxuan Pan1, Xiaodong Ning1
1Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China.
Insights
Modified extracellular vesicles (MmEVs) loaded with thymosin β4 (Tβ4) show promise for heart repair after myocardial infarction (MI). These Tβ4-MmEVs enhance cardiac cell proliferation and reduce fibrosis, offering a new therapeutic avenue for MI adjuvant therapy.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Nanotechnology
Background:
- Cardiac-resident macrophages (cMacs) are crucial for heart health, but their levels decrease post-myocardial infarction (MI).
- Circulating monocyte-derived macrophages do not adequately replace cMacs after MI, and cMac transplantation has limitations.
- Extracellular vesicle (EV) therapy presents a promising alternative for cardiac repair.
Purpose of the Study:
- To develop cell membrane-modified extracellular vesicles (MmEVs) for enhanced cardiac repair post-MI.
- To improve the therapeutic efficacy of MmEVs by loading them with thymosin β4 (Tβ4), creating Tβ4-MmEVs.
- To evaluate the immune evasion, targeted localization, and therapeutic potential of Tβ4-MmEVs in vitro and in vivo.
Main Methods:
- Monocyte membranes were used to modify cardiac-resident macrophage-derived extracellular vesicles (mEVs) to create MmEVs, incorporating CD47 for immune evasion and CCL2 affinity for targeted localization.
- Thymosin β4 (Tβ4) was loaded into MmEVs to create Tβ4-MmEVs for enhanced therapeutic effects.
- In vitro assays assessed cardiomyocyte proliferation and endothelial cell migration, while in vivo studies in MI mice evaluated myocardial fibrosis and vascular density.
Main Results:
- MmEVs and Tβ4-MmEVs demonstrated the ability to promote cardiomyocyte proliferation and endothelial cell migration in vitro.
- MI mice treated with MmEVs and Tβ4-MmEVs showed reduced myocardial fibrosis compared to control groups.
- Treatment with MmEVs and Tβ4-MmEVs led to increased vascular density in the hearts of MI mice.
Conclusions:
- Targeted nanoparticles, specifically Tβ4-MmEVs, hold significant potential as an adjuvant therapy for myocardial infarction.
- These engineered extracellular vesicles offer a feasible and safe alternative for cardiac repair and regeneration.
- The development of therapeutically membrane-modified nanoparticles from homologous origins provides a valuable reference for clinical MI management.
Abstract:
Recent studies have demonstrated the critical role of cardiac-resident macrophages (cMacs) in the maintenance of physiological homeostasis. However, recruitment of circulating monocyte-derived macrophages decreases cMac levels post-myocardial infarction (MI). Transplanting cMacs is not an ideal option due to their low survival rates and the risk of immunological rejection. However, extracellular vesicle therapy has the potential to provide a feasible and safe alternative for cardiac repair. In this study, cell membrane-modified extracellular vesicles (MmEVs) were developed for heart repair by modifying cMac-derived extracellular vesicles (mEVs) with monocyte membranes, resulting in immune evasion and sequential targeted localization to damaged regions through expression of CD47 on MmEVs and strong affinity between monocyte membrane proteins and CCL2. Additionally, to fully exploit the potential clinical application of MmEVs and achieve a better curative effect, thymosin β4 (Tβ4) was loaded into the nanoparticles, resulting in Tβ4-MmEVs. In vitro experiments indicated that both the MmEVs and Tβ4-MmEVs promoted cardiomyocyte proliferation and endothelial cell migration. Animal experiments suggested that MI mice treated with MmEVs and Tβ4-MmEVs exhibited reduced myocardial fibrosis and increased vascular density compared to the control group. Thus, we posit that these targeted nanoparticles hold significant potential for MI adjuvant therapy and may open new avenues for cardiac repair and regeneration. STATEMENT OF SIGNIFICANCE: Extracellular vesicles (EVs) derived from bioactive parent cell sources involved in pathological and repair processes for cardiovascular disease have emerged as a compelling strategy for regenerative therapy. In this study, we constructed monocyte membrane-modified extracellular vesicles loaded with a drug (Tβ4-MmEVs) for heart repair that exhibit extraordinary abilities of immune evasion and sequential localization to damaged regions owing to the presence of CD47 and the strong affinity between monocytes and damaged cardiomyocytes and endothelial cells. The bioactivities of Tβ4-MmEVs on enhancing cardiomyocyte and endothelial cell proliferation were validated both in vitro and in vivo. Effective development and implementation of therapeutically membrane-modified nanoparticles from homologous origins can provide a reference for adjuvant therapy in clinical MI management.
