Human Adipose Stem Cells Engineered to Express Carboxylesterase Confer Anti-Tumoral Efficacy of Irinotecan in Castration-Resistant Prostate Cancer Bone Metastasis Growth and Osteolysis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Purpose Castration-resistant prostate cancer (CRPC) presents a significant clinical challenge, particularly when it metastasizes to bone, leading to skeletal-related events such as osteolysis. Conventional therapies offer limited efficacy and high toxicity, highlighting the need for innovative treatments. This study investigates the use of human telomerase reverse transcriptase-immortalized adipose-derived stem cells engineered to express carboxylesterase (hTERT-ADSC.CE) to enhance the local activation and efficacy of irinotecan (CPT-11) in targeting CRPC. Materials and methods hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells were generated by lentiviral transduction with two genes encoding carboxylesterase enzymes CES1 or CES2 (referred to as CE1 or CE2 in this manuscript), respectively. The migration of hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells toward prostate cancer cells was evaluated in a transwell migration assay. The cytotoxicity of irinotecan in combination with hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells on PC3 prostate cancer cells was assessed via MTT viability and apoptosis assays. An in vivo CRPC bone metastasis model in mice was used to examine the therapeutic effects of co-administered hTERT-ADSC.CE2 cells and CPT-11 on tumor growth and tumor-induced osteolysis. Results hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells demonstrated selective migration toward PC3 cells and significantly e

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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