Abstract
Background aims
Because of their potent immunomodulatory and anti-inflammatory properties, mesenchymal
stromal cells are a major focus in the field of stem cell therapy. However, the precise
mechanisms underlying this are not entirely understood. Human umbilical cord perivascular
cells (HUCPVCs) are a promising cell therapy candidate. This study was designed to
evaluate the time course and mechanisms by which HUCPVCs mitigate lipopolysaccharide
(LPS)-induced systemic and neurological inflammation in immunocompetent mice. To explore
the underlying mechanisms, the authors investigated the biodistribution and fate of
HUCPVCs.
Methods
Male C57BL/6 mice were randomly allocated to four groups: control, LPS, HUCPVCs or
LPS + HUCPVCs. Quantitative polymerase chain reaction, enzyme-linked immunosorbent
assay and cytokine arrays were used to assess changes in pro-inflammatory mediators
systemically and in the brain. Depressive-like behavioral changes were evaluated via
a forced swim test. Quantum dot (qDot) labeling and immunohistochemistry were used
to assess the biodistribution and fate of HUCPVCs and interactions with recipient
innate immune cells.
Results
A single intravenously delivered dose of HUCPVCs significantly reduced the systemic
inflammation induced by LPS within the first 24 h after administration. HUCPVC treatment
abrogated the upregulated expression of pro-inflammatory genes in the hippocampus
and cortex and attenuated depressive-like behavior induced by LPS treatment. Biodistribution
analysis revealed that HUCPVC-derived qDots rapidly accumulated in the lungs and demonstrated
limited in vivo persistence. Furthermore, qDot signals were associated with major recipient innate
immune cells and promoted a shift in macrophages toward a regulatory phenotype in
the lungs.
Conclusions
Overall, this study demonstrates that HUCPVCs can successfully reduce systemic and
neurological inflammation induced by LPS within the first 24 h after administration.
Biodistribution and fate analyses suggest a critical role for the innate immune system
in the HUCPVC-based immunomodulation mechanism.
Key Words
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Article info
Publication history
Published online: December 03, 2022
Accepted:
October 20,
2022
Received:
January 4,
2022
Footnotes
Abbreviations list: HUCPVCs, human umbilical cord perivascular cells; BLC , B lymphocyte chemoattractant; G-CSF, granulocyte colony-stimulating factor; IP-10, interferon gamma-induced protein 10; RANTES, regulated on activation, normal T cell expressed and secreted; TIMP-1, TIMP metallopeptidase inhibitor 1; MCP-1, monocyte chemoattractant protein-1; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion protein 1.
Identification
Copyright
© 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
