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

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

Department of Neuroscience and Experimental Therapeutics

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1521-1535
Number of pages	15
Journal	JACC: Basic to Translational Science
Volume	8
Issue number	12
DOIs	https://doi.org/10.1016/j.jacbts.2023.07.002
State	Published - Dec 2023

All Science Journal Classification (ASJC) codes

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2023.07.002

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Sarkislali, K., Kobayashi, K., Sarić, N., Maeda, T., Henmi, S., Somaa, F. A., Bansal, A., Tu, S. C., Leonetti, C., Hsu, C. H., Li, J., Vyas, P., Kawasawa, Y. I., Tu, T. W., Wang, P. C., Hanley, P. J., Hashimoto-Torii, K., Frank, J. A., Jonas, R. A., & Ishibashi, N. (2023). Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model. JACC: Basic to Translational Science, 8(12), 1521-1535. https://doi.org/10.1016/j.jacbts.2023.07.002

@article{31e969c8b969406ea2d484a573089948,

title = "Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model",

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.",

author = "Kamil Sarkislali and Kei Kobayashi and Nemanja Sari{\'c} and Takuya Maeda and Soichiro Henmi and Somaa, {Fahad A.} and Ankush Bansal and Tu, {Shao Ching} and Camille Leonetti and Hsu, {Chao Hsiung} and Jingang Li and Pranav Vyas and Kawasawa, {Yuka Imamura} and Tu, {Tsang Wei} and Wang, {Paul C.} and Hanley, {Patrick J.} and Kazue Hashimoto-Torii and Frank, {Joseph A.} and Jonas, {Richard A.} and Nobuyuki Ishibashi",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = dec,

doi = "10.1016/j.jacbts.2023.07.002",

language = "English (US)",

volume = "8",

pages = "1521--1535",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

publisher = "Elsevier Inc.",

number = "12",

}

Sarkislali, K, Kobayashi, K, Sarić, N, Maeda, T, Henmi, S, Somaa, FA, Bansal, A, Tu, SC, Leonetti, C, Hsu, CH, Li, J, Vyas, P, Kawasawa, YI, Tu, TW, Wang, PC, Hanley, PJ, Hashimoto-Torii, K, Frank, JA, Jonas, RA & Ishibashi, N 2023, 'Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model', JACC: Basic to Translational Science, vol. 8, no. 12, pp. 1521-1535. https://doi.org/10.1016/j.jacbts.2023.07.002

TY - JOUR

T1 - Mesenchymal Stromal Cell Delivery Via Cardiopulmonary Bypass Provides Neuroprotection in a Juvenile Porcine Model

AU - Sarkislali, Kamil

AU - Kobayashi, Kei

AU - Sarić, Nemanja

AU - Maeda, Takuya

AU - Henmi, Soichiro

AU - Somaa, Fahad A.

AU - Bansal, Ankush

AU - Tu, Shao Ching

AU - Leonetti, Camille

AU - Hsu, Chao Hsiung

AU - Li, Jingang

AU - Vyas, Pranav

AU - Kawasawa, Yuka Imamura

AU - Tu, Tsang Wei

AU - Wang, Paul C.

AU - Hanley, Patrick J.

AU - Hashimoto-Torii, Kazue

AU - Frank, Joseph A.

AU - Jonas, Richard A.

AU - Ishibashi, Nobuyuki

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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DO - 10.1016/j.jacbts.2023.07.002

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AN - SCOPUS:85172186416

SN - 2452-302X

VL - 8

SP - 1521

EP - 1535

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 12

ER -

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

Abstract

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