Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
22 Nov 2023
Historique:
received: 19 12 2022
accepted: 03 11 2023
medline: 24 11 2023
pubmed: 23 11 2023
entrez: 22 11 2023
Statut: epublish

Résumé

While mesenchymal stem cells (MSCs) have gained enormous attention due to their unique properties of self-renewal, colony formation, and differentiation potential, the MSC secretome has become attractive due to its roles in immunomodulation, anti-inflammatory activity, angiogenesis, and anti-apoptosis. However, the precise stimulation and efficient production of the MSC secretome for therapeutic applications are challenging problems to solve. Here, we report on Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs: AIMS. We create an acoustofluidic mechanobiological environment to form reproducible three-dimensional MSC aggregates, which produce the MSC secretome with high efficiency. We confirm the increased MSC secretome is due to improved cell-cell interactions using AIMS: the key mediator N-cadherin was up-regulated while functional blocking of N-cadherin resulted in no enhancement of the secretome. After being primed by IFN-γ, the secretome profile of the MSC aggregates contains more anti-inflammatory cytokines and can be used to inhibit the pro-inflammatory response of M1 phenotype macrophages, suppress T cell activation, and support B cell functions. As such, the MSC secretome can be modified for personalized secretome-based therapies. AIMS acts as a powerful tool for improving the MSC secretome and precisely tuning the secretory profile to develop new treatments in translational medicine.

Identifiants

pubmed: 37993431
doi: 10.1038/s41467-023-43239-6
pii: 10.1038/s41467-023-43239-6
pmc: PMC10665559
doi:

Substances chimiques

Cytokines 0
Anti-Inflammatory Agents 0
Cadherins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7639

Subventions

Organisme : NCI NIH HHS
ID : R33 CA223908
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM141055
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM145960
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Ye He (Y)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Shujie Yang (S)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Pengzhan Liu (P)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Ke Li (K)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Ke Jin (K)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Ryan Becker (R)

Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.

Jinxin Zhang (J)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Chuanchuan Lin (C)

Department of Blood Transfusion, Irradiation Biology Laboratory, Xinqiao Hospital, Chongqing, 400037, China.

Jianping Xia (J)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Zhehan Ma (Z)

Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.

Zhiteng Ma (Z)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Ruoyu Zhong (R)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.

Luke P Lee (LP)

Harvard Medical School, Harvard University, Renal Division and Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA. lplee@bwh.harvard.edu.
Department of Bioengineering, University of California, Berkeley, Berkeley, CA, 94720, USA. lplee@bwh.harvard.edu.
Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA, 94720, USA. lplee@bwh.harvard.edu.
Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Korea. lplee@bwh.harvard.edu.
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, Korea. lplee@bwh.harvard.edu.

Tony Jun Huang (TJ)

Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA. tony.huang@duke.edu.

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