Distinctive Cellular Transcriptomic Signature and MicroRNA Cargo of Extracellular Vesicles of Horse Adipose and Endometrial Mesenchymal Stem Cells from the Same Donors.

The study explores the distinct genetic markers and microRNA contents of extracellular vesicles in equine endometrial and adipose mesenchymal stem cells from the same donor. These findings may essentially impact the potential therapeutic use of these horse stem cells.

Study Methodology

• The researchers isolated equine endometrial and adipose mesenchymal stem cells (eMSCs and aMSCs respectively) from the same thoroughbred mare donors. The cells exhibited key features of MSCs, including the ability to differentiate into three types of mesodermal lineages as well as neural lineages.
• The influence of the origin of cells on their transcriptome profile was evaluated. The research team isolated cellular RNA and sequenced it, while the extracellular vesicles (EVs) were obtained from the conditioned medium of cells cultured in an environment depleted of EVs.
• The microRNA (miRNA) cargo of the EVs was analyzed through sequencing. The researchers then analyzed the differential expression of mRNAs and EV-miRNA, and identified the pathways and processes most represented in each cell origin.

Study Findings

• The mRNA reads from all expressed genes clustered according to their cellular origin. The research revealed notable differences in the number of up- and down-regulated genes, identifying 125 upregulated genes and 51 downregulated genes, and 31 differentially expressed miRNAs.
• Endometrial MSCs showed significant upregulation of genes involved in the Hippo, transforming growth factor beta, and pluripotency signaling pathways. Concurrently, the pathways related to extracellular matrix reorganization were highly represented in the miRNA cargo of EVs secreted by eMSCs.
• The study concluded that the original tissue niche from which the MSCs were derived, significantly impacted the transcriptomic signature of the cells.
• This niche-specific influence also affected the secretion of EVs loaded with lineage-specific miRNA, which plays a crucial role in effective cellular communication and homeostasis.

Implication of the Study

• These findings may enhance our understanding of the unique functional characteristics of MSCs derived from different tissue environments.
• This knowledge, in turn, could be used to identify and test the biological functions of these cells, providing new tools for their therapeutic use, potentially leading to advancements in the field of regenerative medicine and stem cell therapy.