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CD73⁺ Mesenchymal Stem Cells Ameliorate Myocardial Infarction by Promoting Angiogenesis.

ABSTRACT: With multipotent differentiation potential and paracrine capacity, mesenchymal stem cells (MSCs) have been widely applied in clinical practice for the treatment of ischemic heart disease. MSCs are a heterogeneous population and the specific population of MSCs may exhibit a selective ability for tissue repair. The aim of our research was to adapt the CD73⁺ subgroup of adipose derived MSCs (AD-MSCs) for the therapy of myocardial infarction (MI). In this research, AD-MSCs were isolated from adipose tissue surrounding the groin of mice and CD73⁺ AD-MSCs were sorted using flow cytometry. To investigate the therapeutic effects of CD73⁺ AD-MSCs, 1.2 × 10⁶ CD73⁺ AD-MSCs were transplanted into rat model of MI, and CD73^- AD-MSCs, normal AD-MSCs transplantation served as control. Our results revealed that CD73⁺ AD-MSCs played a more effective role in the acceleration function of cardiac recovery by promoting angiogenesis in a rat model of MI compared with mixed AD-MSCs and CD73^- AD-MSCs. Moreover, with the expression of CD73 in AD-MSCs, the secretion of VEGF, SDF-1α, and HGF factors could be promoted. It also shows differences between CD73⁺ and CD73^- AD-MSCs when the transcription profiles of these two subgroups were compared, especially in VEGF pathway. These findings raise an attractive outlook on CD73⁺ AD-MSCs as a dominant subgroup for treating MI-induced myocardial injury. CD73, a surface marker, can be used as a MSCs cell quality control for the recovery of MI by accelerating angiogenesis.

SUBMITTER: Li Q

PROVIDER: S-EPMC8152667 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSpinal cord injury (SCI) is an inflammatory condition, and excessive adenosine triphosphate (ATP) is released into the extracellular space, which can be catabolized into adenosine by CD73. Extracellular vesicles have been designed as nano drug carriers in many diseases. However, their impacts on delivery of CD73 after SCI are not yet known. We aimed to construct CD73 modified extracellular vesicles and explore the anti-inflammatory effects after SCI.MethodsCD73 engineered extracellular vesicles (CD73+ hucMSC-EVs) were firstly established, which were derived from human umbilical cord mesenchymal stem cells (hucMSCs) transduced by lentiviral vectors to upregulate the expression of CD73. Effects of CD73+ hucMSC-EVs on hydrolyzing ATP into adenosine were detected. The polarization of M2/M1 was verified by immunofluorescence. Furthermore, A2aR and A2bR inhibitors and A2bR knockdown cells were used to investigate the activated adenosine receptor. Biomarkers of microglia and levels of cAMP/PKA were also detected. Repetitively in vivo study, morphology staining, flow cytometry, cytokine analysis, and ELISA assay, were also applied for verifications.ResultsCD73+ hucMSC-EVs reduced concentration of ATP and promoted the level of adenosine. In vitro experiments, CD73+ hucMSC-EVs increased macrophages/microglia M2:M1 polarization, activated adenosine 2b receptor (A2bR), and then promoted cAMP/PKA signaling pathway. In mice using model of thoracic spinal cord contusion injury, CD73+ hucMSC-EVs improved the functional recovery after SCI through decreasing the content of ATP in cerebrospinal fluid and improving the polarization from M1 to M2 phenotype. Thus, the cascaded pro-inflammatory cytokines were downregulated, such as TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokines were upregulated, such as IL-10 and IL-4.ConclusionsCD73+ hucMSC-EVs ameliorated inflammation after spinal cord injury by reducing extracellular ATP, promoting A2bR/cAMP/PKA pathway and M2/M1 polarization. CD73+ hucMSC-EVs might be promising nano drugs for clinical application in SCI therapy.

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CD73⁺ Mesenchymal Stem Cells Ameliorate Myocardial Infarction by Promoting Angiogenesis.

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Dataset Information

CD73+ Mesenchymal Stem Cells Ameliorate Myocardial Infarction by Promoting Angiogenesis.

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OmicsDI is part of the ELIXIR infrastructure

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CD73⁺ Mesenchymal Stem Cells Ameliorate Myocardial Infarction by Promoting Angiogenesis.