Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model

Kamil Sarkislali; Kei Kobayashi; Nemanja Sarić; Takuya Maeda; Soichiro Henmi; Fahad A Somaa; Ankush Bansal; Shao Ching Tu; Camille Leonetti; Chao-Hsiung Hsu; Jingang Li; Pranav Vyas; Yuka Imamura Kawasawa; Tsang-Wei Tu; Paul C Wang; Patrick J Hanley; Kazue Hashimoto-Torii; Joseph A Frank; Richard A Jonas; Nobuyuki Ishibashi

doi:10.1016/j.jacbts.2023.07.002

Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model

JACC Basic Transl Sci. 2023 Sep 6;8(12):1521-1535. doi: 10.1016/j.jacbts.2023.07.002. eCollection 2023 Dec.

Authors

Kamil Sarkislali^{1

2}, Kei Kobayashi^{1

2

3}, Nemanja Sarić^{1

2}, Takuya Maeda^{1

2}, Soichiro Henmi^{1

2

3}, Fahad A Somaa^{1

2}, Ankush Bansal¹, Shao Ching Tu^{1

2}, Camille Leonetti^{1

2}, Chao-Hsiung Hsu⁴, Jingang Li^{1

2}, Pranav Vyas^{5

6}, Yuka Imamura Kawasawa⁷, Tsang-Wei Tu⁴, Paul C Wang^{4

8}, Patrick J Hanley^{6

9}, Kazue Hashimoto-Torii^{1

6

10}, Joseph A Frank^{11

12}, Richard A Jonas^{1

2

3

6}, Nobuyuki Ishibashi^{1

2

3

6

10}

Affiliations

¹ Center for Neuroscience Research, Children's National Hospital, Washington, DC, USA.
² Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
³ Children's National Heart Institute, Children's National Hospital, Washington, DC, USA.
⁴ Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington, DC, USA.
⁵ Department of Radiology, Children's National Hospital, Washington, DC, USA.
⁶ Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
⁷ Departments of Pharmacology and Biochemistry and Molecular Biology, Institute for Personalized Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA.
⁸ Department of Electrical Engineering, Fu Jen Catholic University, New Taipei City, Taiwan.
⁹ Program for Cell Enhancement and Technologies for Immunotherapy, Division of Blood and Marrow Transplantation, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
¹⁰ Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
¹¹ Frank Laboratory, Radiology and Imaging Sciences, National Institutes of Health; Bethesda, Maryland, USA.
¹² National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Oxidative/inflammatory stresses due to cardiopulmonary bypass (CPB) cause prolonged microglia activation and cortical dysmaturation, thereby contributing to neurodevelopmental impairments in children with congenital heart disease (CHD). This study found that delivery of mesenchymal stromal cells (MSCs) via CPB minimizes microglial activation and neuronal apoptosis, with subsequent improvement of cortical dysmaturation and behavioral alteration after neonatal cardiac surgery. Furthermore, transcriptomic analyses suggest that exosome-derived miRNAs may be the key drivers of suppressed apoptosis and STAT3-mediated microglial activation. Our findings demonstrate that MSC treatment during cardiac surgery has significant translational potential for improving cortical dysmaturation and neurological impairment in children with CHD.

Keywords: cardiac surgery; cardiopulmonary bypass; congenital heart disease; mesenchymal stromal cells; neuroprotection.

Abstract

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