Gene expression profiles of angiogenesis markers and microRNA-128 from the secretome of umbilical cord mesenchymal stem cells from Macaca fascicularis

TL;DR

This study shows that low oxygen conditions increase the production of healing-related molecules in stem cells from macaque umbilical cords, which could help treat ischemic stroke.

Contribution

The study identifies optimal hypoxic conditions to enhance the expression of angiogenic and anti-apoptotic markers in UC-MSC secretomes.

Findings

Hypoxia significantly increased VEGF, MCP-1, and miRNA-128 expression in UC-MSC secretomes.

MMP-2 expression was highest under normoxic conditions and reduced under hypoxia.

miRNA-128 was predominantly secreted under hypoxic conditions.

Abstract

Angiogenesis and anti-apoptosis play crucial roles in ischemic stroke recovery. The mesenchymal stem cell (MSC) secretome, rich in bioactive molecules, presents a promising therapeutic avenue. However, optimizing the culture conditions to enhance the expression of angiogenic markers remains a challenge. This study examines the effect of hypoxic preconditioning on the expression of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), and microRNA (miRNA-128) in the secretome of umbilical cord-derived MSCs (UC-MSCs) from Macaca fascicularis.

UC-MSCs were cultured under normoxic (21% O2) and hypoxic conditions (1%, 3%, and 5% O2) for 48 h. The secretome was isolated, and reverse transcription-quantitative polymerase chain reaction was used to quantify the expression of VEGF, MCP-1, MMP-2, and miRNA-128. Expression levels were normalized to housekeeping genes and analyzed using statistical methods to determine significant differences among groups.

Hypoxic preconditioning significantly upregulated VEGF (1% O2), MCP-1 (5% O2), and miRNA-128 (5% O2) expression compared to normoxic conditions. Conversely, MMP-2 expression was highest in normoxic conditions and downregulated under hypoxia. In addition, miRNA-128 was found to be predominantly secreted into the extracellular space under hypoxic conditions rather than retained within cells.

Hypoxic preconditioning effectively modulates the expression of key angiogenesis and anti-apoptotic markers in UC-MSCs. The study highlights the importance of optimizing oxygen levels to enhance the therapeutic potential of MSC-derived secretomes for ischemic stroke treatment. Future research should focus on in vivo validation and clinical translation of these findings.

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