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Remote Transplantation of Human Adipose‐derived Stem Cells Induces Regression of Cardiac Hypertrophy by Regulating the Macrophage Polarization in Spontaneously Hypertensive Rats
Author(s) -
Lee TsungMing,
Yang ChenChia
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.771.1
Subject(s) - medicine , muscle hypertrophy , transplantation , stem cell , paracrine signalling , adipose tissue , pressure overload , endocrinology , left ventricular hypertrophy , cardiology , biology , microbiology and biotechnology , blood pressure , cardiac hypertrophy , receptor
Left ventricular hypertrophy in hypertension has prognostic significance on cardiovascular mortality and morbidity. Cardioprotection by stem cell therapy can be evoked through extracardiac paracrine approaches. Recently, we have shown that butylidenephthalide (BP) improves adipose‐derived stem cell (ADSC) engraftment via attenuated reactive oxygen species (ROS) production. This prompted us to investigate whether remote transplantation of stem cells confers attenuated left ventricular hypertrophy at an established phase of hypertension. Male spontaneously hypertensive rats (SHRs) aged 12 weeks were randomly allocated to receive hamstring injection of vehicle, ADSCs, and BP‐preconditioned ADSCs for 8 weeks. As compared with untreated SHRs, naïve ADSCs decreased the ratio of left ventricular to body weight, cardiomyocyte cell size, and collagen deposition independent of hemodynamic changes. These changes were accompanied by attenuated myocardial ROS production and increased p‐STAT3 levels. At day 3 after implantation into the right hamstring muscle, SHR treated with vehicle was associated with increased myocardial M1 macrophage infiltration, which can be inhibited by either naïve ADSCs or BP‐preconditioned ADSCs. However, compared with naïve ADSCs, BP‐preconditioned ADSCs provided a further decrease of ROS and left ventricular hypertrophy and an increase of local ADSC engraftment, STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL‐10 levels and the percentage of M2 macrophage infiltration. SIN‐1 or 3SI‐201 reversed the effects of BP‐preconditioned ADSCs increase on myocardial IL‐10 levels. Furthermore, SIN‐1 abolished the phosphorylation of STAT3, whereas superoxide levels were not affected following the inhibition of STAT3. Our results highlighted the feasibility of remote transplantation of ADSCs can be considered as an alternative procedure to reverse cardiac hypertrophy. BP‐pretreated ADSCs polarize macrophages into M2 immunoregulatory cells more efficiently than naïve ADSCs via ROS/STAT3 pathway. Support or Funding Information nil This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .