Fate of intravenously administered umbilical cord mesenchymal stromal cells and interactions with the host's immune system

Amadeo, Francesco ORCID: 0000-0002-3868-2348, Hanson, Vivien, Liptrott, Neill J ORCID: 0000-0002-5980-8966, Wilm, Bettina ORCID: 0000-0002-9245-993X, Murray, Patricia and Taylor, Arthur ORCID: 0000-0003-2028-6694 (2023) Fate of intravenously administered umbilical cord mesenchymal stromal cells and interactions with the host's immune system. BIOMEDICINE & PHARMACOTHERAPY, 159. 114191-.

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Abstract

Mesenchymal stromal cells (MSCs) are multipotent cells showing promise in pre-clinical studies and currently used in many clinical trials. The regenerative potential of MSCs is mediated, at least in part, by direct and indirect immunomodulatory processes. However, the mechanism of action is not fully understood yet, and there are still concerns about possible undesired negative effects associated with the administration of living cells. In this study, we (i) compare the long-term fate and safety of umbilical cord (UC-)MSCs administered to immunocompetent and immunocompromised (severe combined immunodeficient (SCID) and non-obese diabetic (NOD)/SCID) animals, and (ii) investigate the immunological response of the host to the administered cells. Intravenous administration of firefly luciferase expressing UC-MSCs revealed that the cells get trapped in the lungs of both immunocompetent and immunocompromised animals, with > 95% of the cells disappearing within 72 h after administration. In 27% of the SCID and 45% of the NOD/SCID, a small fraction of the cells lived up to day 14 but in most cases they all disappeared earlier. One NOD/SCID mouse showed a weak signal up to day 31. Immunocompetent mice displayed elevated percentages of neutrophils in the lungs, the blood, and the spleen 2 h after the administration of the cells. The concentration of neutrophil chemoattractants (MCP1, CCL7, Gro-α and IP-10) were also increased in the plasma of the animals 2 h after the administration of the MSCs. Our results suggest that although the UC-MSCs are short-lived in mice, they still result in an immunological response that might contribute to a therapeutic effect.

Item Type:	Article
Uncontrolled Keywords:	Mesenchymal stromal cells, Cell therapies, Bioluminescence imaging, Reporter genes, Animal models
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	10 Jan 2023 09:36
Last Modified:	21 Feb 2023 12:33
DOI:	10.1016/j.biopha.2022.114191
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3166940