Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel
The main goal in cancer chemotherapy is to drive the drug into the tumor microenvironment to kill as many cancer cells as
possible while producing the lowest collateral toxicity. Previously, we have shown that human bone marrow derived mesenchymal
stromal cells (hBM-MSCs) exposed to Paclitaxel (PTX) were able to uptake and subsequently release the drug in the culture medium.
PTX primed hBM-MSCs (hBM-MSCsPTX) located in the vicinity of cancer cells produced a strong inhibition of tumor cell growth both
in vitro and in vivo. To expand these observations, in the present study we exposed human skin derived fibroblasts (hSDFs) to 2,000
ng/ml of PTX and then tested both cells and their conditioned medium (CM) in vitro for their capacity to inhibit the proliferation of
human tumor cell lines (MOLT-4, DU-145, U87-MG, SH-SY5Y(+) and LAN-5). We found that hSDFs primed with PTX (hSDFsPTX)
were able to uptake and subsequently release PTX in a time dependent manner. hSDFsPTX-derived CM(hSDFsPTX-CM) from 1:4 to
1:10 dilutions produced a significant (p<0.05) in vitro tumor growth inhibition. hSDFsPTX co-cultured with leukemia cells at 1:1 to 1:10
ratio, completely inhibited cells growth whereas no inhibition was induced by normal hSDFs cells. Our results demonstrate for the first
time that hSDFs can be loaded in vitro with PTX and thus can acquire a potent anti-tumor activity. Since hSDFs can be easily isolated
from skin biopsies without any particular pain and discomfort to donor patients, we conclude that hSDFs may represent a valid cell type
option for carrying and delivering anti-cancer drugs.
Keywords: Drug uptake, Mesenchymal stem cells, Skin dermal fibroblasts, Stromal cells, Taxol
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