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Novel Therapeutic Approach Using Drug-loaded Adipose-derived Stem Cells for Pancreatic Cancer.

ABSTRACT: We developed anticancer drug-conjugated biodegradable polymer-nanoparticle-loaded adipose-derived stem cells (AdSCs) as a tool for biodrug delivery systems for cancer therapy. Pirarubicin was conjugated in polylactic/glycolic acid (PLGA) followed by formation of nanoparticles (NPs), which were loaded with human AdSCs and cocultured. The pirarubicin-conjugated PLGA NP-loaded AdSCs (PirNP-AdSCs) were overall viable within 48 h and exhibited significantly enhanced migration activity. We confirmed that pirarubicin was gradually released into the culture medium from PirNP-AdSCs, and the conditioned medium significantly inhibited the proliferation activity and induced the apoptosis of human pancreatic cancer cells (KP1N). PirNP-AdSCs also significantly induced tumor cell apoptosis in an ex vivo culture system with KP1N-derived tumors, and there was increased invasion/migration of PirNP-AdSCs inside the tumor. Finally, we compared the therapeutic efficacy of the PirNP-AdSCs on KP1N-derived tumor growth with that of treatments of AdSCs alone, PirNPs alone or normal saline (control) in immunodeficient mice. Subcutaneous local administration of PirNP-AdSCs significantly inhibited tumor growth, inducing the apoptosis of tumor cells and vasculature compared with the other groups. The present therapeutic strategy might give rise to a novel cancer therapy minimizing the adverse side effects of anticancer drugs in patients who suffer from cancer.

SUBMITTER: Aoki M

PROVIDER: S-EPMC6884490 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAnal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury.DesignMale rabbits were assigned to equal groups (n?=?7) including control, sphincterotomy, sphincterotomy treated with laser (660?nm, 90 s, immediately after sphincterotomy, daily, 14?days), hADSCs (2?×?106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser?+?hADSCs. Ninety?days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed.ResultsThe laser?+?hADSCs group had a higher resting pressure compared with the sphincterotomy (p?<?0.0001), laser (p?<?0.0001), and hADSCs (p?=?0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p?<?0.0001), without a significant difference between treatments (p?>?0.05). In the laser?+?hADSCs group, motor unit numbers were higher than those in the laser group (p?<?0.0001) but did not differ from the hADSCs group (p?=?0.075). Sphincterotomy increased collagen content, but the muscle content (p?=?0.36) and collagen content (p?=?0.37) were not significantly different between the laser?+?hADSCs and control groups. Laser?+?hADSCs increased ACTA1 (p?=?0.001) and MHC (p?<?0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p?=?0.009) and Ki67 mRNA expression (p?=?0.01) and decreased vimentin mRNA expression (p?<?0.0001) compared with laser.ConclusionThe combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

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Novel Therapeutic Approach Using Drug-loaded Adipose-derived Stem Cells for Pancreatic Cancer.

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