Umbilical cord mesenchymal stromal cell-derived extracellular vesicles lack the potency to immunomodulate human monocyte-derived macrophages in vitro

被引:2
作者
da Silva, Tamiris Borges [1 ]
Rendra, Erika [2 ]
David, Christopher A. W. [5 ]
Bieback, Karen [2 ,3 ]
Cross, Michael J. [4 ]
Wilm, Bettina [1 ]
Liptrott, Neill J. [5 ]
Murray, Patricia [1 ]
机构
[1] Univ Liverpool, Dept Mol Physiol & Cell Signalling, Inst Syst Mol & Integrat Biol, Crown St, Liverpool L69 3GE, England
[2] Heidelberg Univ, Inst Transfus Med & Immunol, Mannheim Inst Innate Immunoscience, Med Fac Mannheim, D-68167 Mannheim, Germany
[3] Heidelberg Univ, Inst Innate Immunoscience, Med Fac Mannheim, Mannheim, Germany
[4] Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3GL, England
[5] Univ Liverpool, Inst Syst Mol & Integrat Biol, Dept Pharmacol & Therapeut, Immunocompatibil Grp, Liverpool, England
基金
英国惠康基金;
关键词
UK; Extracellular vesicles; Mesenchymal stromal cells; Macrophages; Monocytes; Cell therapies; Immunomodulation; STEM-CELLS; RENAL INJURY; KIDNEY; REPAIR; POLARIZATION; ACTIVATION; EXOSOMES; IMMUNE; INFLAMMATION; MECHANISM;
D O I
10.1016/j.biopha.2023.115624
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Mesenchymal stromal cells (MSCs) have been reported to display efficacy in a variety of preclinical models, but without long-term engraftment, suggesting a role for secreted factors, such as MSC-derived extracellular vesicles (EVs). MSCs are known to elicit immunomodulatory effects, an important aspect of which is their ability to affect macrophage phenotype. However, it is not clear if these effects are mediated by MSC-derived EVs, or other factors secreted by the MSCs. Here, we use flow cytometry to assess the effects of human umbilical cord (hUC) MSC-derived EVs on the expression of pro-inflammatory (CD80) and anti-inflammatory (CD163) surface markers in human monocyte-derived macrophages (hMDMs). hUC-MSC-derived EVs did not change the surface marker expression of the hMDMs. In contrast, when hMDMs were co-incubated with hUC-MSCs in indirect co-cultures, changes were observed in the expression of CD14, CD80 and CD163, particularly in M1 macrophages, suggesting that soluble factors are necessary to elicit a shift in phenotype. However, even though EVs did not alter the surface marker expression of macrophages, they promoted angiogenesis and phagocytic capacity increased proportionally to increases in EV concentration. Taken together, these results suggest that hUC-MSC-derived EVs are not sufficient to alter macrophage phenotype and that additional MSC-derived factors are needed.
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页数:11
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