Abstract
Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor model. Then, we observed that hUCMSC-derived extracellular vesicles (hUCMSC-EVs) contribute to the hUCMSC-promoted LUAD cell growth through a direct effect on LUAD cells. Furthermore, we showed that hUCMSC-EV-mediated LUAD growth is associated with increased proliferation and decreased apoptosis in LUAD cells, concomitant with reduced PTEN expression mediated by the hUCMSC-EV-transmitted miR-410. Our findings provide novel insights into the intercellular communications between cancer cells and MSCs through MSC-EV-miRNA and suggest that modification of hUCMSC-EVs might be an attractive therapeutic option for the clinical application of hUCMSC-EVs that would reduce unwanted side effects.
Highlights
Mesenchymal stem cells (MSCs) are multipotent cells that reside in various tissues and have the potentials to differentiate into mesenchymal cells, including osteoblasts, adipocytes, and chondrocytes[1]
We investigated whether EVs were responsible for the pro-growth activity of human umbilical cord MSCs (hUCMSCs)
These results suggest that hUCMSC-EVs contribute to the hUCMSC-promoted lung adenocarcinoma (LUAD) cell growth
Summary
Mesenchymal stem cells (MSCs) are multipotent cells that reside in various tissues and have the potentials to differentiate into mesenchymal cells, including osteoblasts, adipocytes, and chondrocytes[1]. Bone marrow-derived MSCs (BM-MSCs) are the most common cell source, especially in animal-based experiments, for tissue repair, engineering, and vehicles for cellbased gene therapy. The clinical application of BM-MSCs is limited due to the invasive nature of the sample collection, low cell yield, reduced proliferation, and differentiation capacities in aging donors[6], and some existing ethical concerns. Unlike BM-MSCs, human umbilical cord-derived MSCs (hUCMSCs) are viewed as a better choice of MSCs for clinical application due to the painless collection procedure, high cell vitality, low immunogenicity, high paracrine potential for accelerating injury tissue repair processes, and the absence of ethical issues[7,8]. Banks of hUCMSCs are being set up in many countries[9]
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