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<p>One of the regenerative medicine approaches for severe heart failure (HF) involves enhancing the inherent regenerative capacity, with mesenchymal stem cells (MSCs) being a crucial element. High mobility group box 1 (HMGB1) has been reported to promote the mobilization of MSCs from the bone marrow and contribute to tissue repair. We hypothesized that cardiac function would improve through this mechanism in a porcine ischemic cardiomyopathy (ICM) model and analyzed its effectiveness using various imaging modalities, histological analyses, and RT-PCR. Echocardiography revealed an increased left ventricular (LV) ejection fraction and reduced LV end-systolic volume. Cardiac magnetic resonance imaging with late gadolinium enhancement demonstrated improved regional LV strain and a smaller scarred myocardial zone. A pressure wire study in the coronary arteries showed enhanced coronary flow reserve and resistive reserve ratio. Histological analysis exhibited a smaller cardiomyocyte diameter, reduced fibrosis area, and an increased number of CD31-positive endothelial cells. RT-PCR analysis indicated elevated levels of pro-angiogenic, anti-fibrotic, and anti-inflammatory factors such as SDF1, HGF, FGF2, and TGFb3. These findings suggested that HMGB1 fragment activated a self-tissue repair pathway, leading to improved cardiac function. The less-invasive intravenous administration of the HMGB1 fragment highlights its potential as a regenerative therapy for severe HF.</p>

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Intravenous high mobility group box 1 fragment improves cardiac function, fibrosis, and coronary flow in porcine ischemic cardiomyopathy model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月11日

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  • Yoshito Ito,
  • Masashi Kawamura,
  • Takuji Kawamura,
  • Katsuto Tamai,
  • Daisuke Yoshioka,
  • Ryohei Matsuura,
  • Ai Kawamura,
  • Yusuke Misumi,
  • Akima Harada,
  • Tadashi Watabe,
  • Takasumi Goto,
  • Atsushi Yamada,
  • Hisakazu Ogita,
  • Masaki Taira,
  • Kazuo Shimamura,
  • Shigeru Miyagawa

摘要

One of the regenerative medicine approaches for severe heart failure (HF) involves enhancing the inherent regenerative capacity, with mesenchymal stem cells (MSCs) being a crucial element. High mobility group box 1 (HMGB1) has been reported to promote the mobilization of MSCs from the bone marrow and contribute to tissue repair. We hypothesized that cardiac function would improve through this mechanism in a porcine ischemic cardiomyopathy (ICM) model and analyzed its effectiveness using various imaging modalities, histological analyses, and RT-PCR. Echocardiography revealed an increased left ventricular (LV) ejection fraction and reduced LV end-systolic volume. Cardiac magnetic resonance imaging with late gadolinium enhancement demonstrated improved regional LV strain and a smaller scarred myocardial zone. A pressure wire study in the coronary arteries showed enhanced coronary flow reserve and resistive reserve ratio. Histological analysis exhibited a smaller cardiomyocyte diameter, reduced fibrosis area, and an increased number of CD31-positive endothelial cells. RT-PCR analysis indicated elevated levels of pro-angiogenic, anti-fibrotic, and anti-inflammatory factors such as SDF1, HGF, FGF2, and TGFb3. These findings suggested that HMGB1 fragment activated a self-tissue repair pathway, leading to improved cardiac function. The less-invasive intravenous administration of the HMGB1 fragment highlights its potential as a regenerative therapy for severe HF.