Stromal cell-derived factor-encapsulated nanoparticles target ischemic myocardium and attenuate myocardial injury via proangiogenic effects

Shin Yajima¹, Seung Hyun Lee², Junkai Yang², Matthew D Vergel², Manoj K Manna³, Sho Kusadokoro², Yuanjia Zhu⁴, Stefan Elde⁵, Danielle M Mullis⁵, Akshay Venkatesh², Sidarth Ethiraj², Tsuyoshi Ueyama⁶, Hiroyuki Takashima⁶, Samuel E Oh², Chris Huynh², Hanjay Wang⁵, Yasuhiro Shudo⁵, Shigeru Miyagawa⁷, Yoshiki Sawa⁷, Jayakumar Rajadas⁸, Y Joseph Woo⁹

Affiliations

¹ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
² Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
³ Materials Science & Engineering, Stanford University, Stanford, CA, 94305, USA.
⁴ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁵ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
⁶ Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
⁷ Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
⁸ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA.
⁹ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: joswoo@stanford.edu.

PMID: 39947060
DOI: 10.1016/j.biomaterials.2025.123167

Free article

Stromal cell-derived factor-encapsulated nanoparticles target ischemic myocardium and attenuate myocardial injury via proangiogenic effects

Shin Yajima et al. Biomaterials. 2025 Jul.

Free article

. 2025 Jul:318:123167.

doi: 10.1016/j.biomaterials.2025.123167. Epub 2025 Feb 4.

Authors

Affiliations

¹ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
² Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
³ Materials Science & Engineering, Stanford University, Stanford, CA, 94305, USA.
⁴ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁵ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
⁶ Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
⁷ Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
⁸ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA.
⁹ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: joswoo@stanford.edu.

PMID: 39947060
DOI: 10.1016/j.biomaterials.2025.123167

Abstract

Lipid bilayer nanoparticles (NPs) with and without stromal cell-derived factor (SDF) were created to target and treat ischemia/reperfusion (I/R)-injured myocardium. Male Wistar rats were subjected to myocardial I/R insult and, at reperfusion, randomized to receive systemic injections of 5 mL/kg PBS, 6 μg/kg of NPs, SDF, or SDF-NPs. Four days after treatment, SDF-NPs circulated and accumulated selectively in the ischemic myocardium, with an SDF concentration roughly three times that of the other three treatments. SDF-NP-treated rats had more endothelial progenitor cells (EPCs) in the blood and preserved capillaries and arterioles in the ischemic border myocardium four weeks post-treatment, which improved microvascular perfusion, reduced fibrosis, and preserved heart function. Notably, hearts treated with SDF-NPs retained left ventricular function at four weeks compared to 1-day post-treatment, with a 2.7 ± 1.2 % increase in the ejection fraction. The other three treatments decreased left ventricular function at four weeks (PBS: -7.8 ± 1.2 %, P < 0.001; empty NPs: -3.9 ± 1.3 %, P = 0.004; SDF solution: -5.1 ± 1.3 %, P = 0.001). Hence, systemically injected SDF-NPs selectively accumulate in ischemic cardiac tissue, shielding the myocardium from I/R injury via angiogenic effects through increased EPC migration. This novel cardioprotective drug may be clinically translatable.

Keywords: Angiogenesis; Endothelial progenitor cell; Ischemia-reperfusion injury; Nanoparticle; Stromal cell-derived factor.

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Conflict of interest statement

Declaration of competing interest The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal of Thoracic and Cardiovascular Surgery (JW), Journal of the American College of Cardiology (JW), and Circulation (JW)] and was not involved in the editorial review or the decision to publish this article. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by the National Institutes of Health (NIH R01 HL 089315–11, YJW; NIH F32 HL158151, YZ; NIH F32 HL170741, SE); the Thoracic Surgery Foundation Research Fellowship (SY), and the Thoracic Surgery Foundation Resident Research Fellowship (YZ). The content is the sole responsibility of the authors and does not necessarily represent the official views of the funders.

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Stromal cell-derived factor-encapsulated nanoparticles target ischemic myocardium and attenuate myocardial injury via proangiogenic effects

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Stromal cell-derived factor-encapsulated nanoparticles target ischemic myocardium and attenuate myocardial injury via proangiogenic effects

Authors

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Abstract

Conflict of interest statement

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