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Adv Pharm Bull. 2024;14(2): 434-444.
doi: 10.34172/apb.2024.027
PMID: 39206409
PMCID: PMC11347737
  Abstract View: 461
  PDF Download: 223

Research Article

Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides

Ika Adhani Sholihah 1 ORCID logo, Anggraini Barlian 1,2* ORCID logo

1 School of Life Sciences and Technology, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung 40132, Indonesia.
2 Research Center for Nanosciences and Nanotechnology, Institut Teknologi Bandung, Bandung, West Java 40132, Indonesia.
*Corresponding Author: Anggraini Barlian, Email: anggrainibarlian@gmail.com

Abstract

Purpose: At present, therapeutic interventions to treat acute lung injury (ALI) remain largely limited to lung-protective strategies, as no real molecular-driven therapeutic intervention has yet become available. The administration of bacterial lipopolysaccharides (LPS) is known as an inflammatory activator, representing a frequently used model of ALI. This study investigated the biological function of normoxic (21% O2 ) vs. hypoxic conditions (5% O2 ) obtained from human Wharton’s Jelly mesenchymal stem cells (hWJ-MSCs) and discovered that exosomes have the ability to suppress inflammatory responses by specifically targeting TNF-α, IL-1β, IL-6. and identify the toll-like receptor 4 (TLR4) NF-κβ gene expression.

Methods: Primer culture hWJ-MSCs characterization with trilineage differentiation and CD markers was conducted. To obtain exosomes, hWJ-MSCs were stimulated with two different oxygen levels: 21% (nor-exo) and 5% (hypo-exo). Then, the L2 cell line was induced with LPS 1 µg/mL. Inflamed-L2 was treated with nor-exo, hypo-exo, and dexamethasone as a positive control. The RNA extracted from treated L2 cells was utilized to examine the gene expression profiles of TLR4 and NF-κβ, and the medium was used to measure tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 levels using ELISA. Lastly, proteomic analysis of the exosome using LC/MS-MS was conducted.

Results: Nor-exo and hypo-exo can be characterized and can produce higher yields exosomes under hypoxic conditions. The expression of TLR4 and NF-κβ genes and the proinflammatory levels such as IL-6, IL-1β, and TNF-α levels in nor-exo and hypo-exo treatments decreased.

Conclusion: Nor-exo and hypo-exo derived from hWJ-MSCs were proven to have anti-inflammatory activities.

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Submitted: 31 May 2023
Revision: 05 Jan 2024
Accepted: 07 Jan 2024
ePublished: 13 Jan 2024
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