Paclitaxel impairs adipose stem cell proliferation and differentiation

Area of Science:

• Regenerative Medicine
• Cancer Biology
• Stem Cell Biology

Background:

• Chemotherapy-induced immunosuppression in cancer patients leads to impaired surgical wound healing.
• Human adipose-derived stem cells (hASCs) show promise for improving wound healing through neovascularization and accelerated closure.
• The impact of chemotherapy on hASC function for wound healing applications is currently unknown.

Purpose of the Study:

• To investigate the effects of paclitaxel, a common chemotherapeutic agent, on the viability, proliferation, multipotency, and apoptosis of hASCs.
• To determine if paclitaxel affects key differentiation pathways in hASCs, particularly endothelial differentiation crucial for neovascularization.
• To explore the potential role of Tumor Necrosis Factor-alpha (TNF-α) in paclitaxel-induced hASC dysfunction.

Main Methods:

• hASCs were isolated from chemotherapy-naive patients.
• Cytotoxicity, proliferation (MTT, EdU assays), and apoptosis (Annexin V assay) were assessed after paclitaxel treatment.
• Differentiation potential (adipogenic, osteogenic, endothelial) was analyzed using specific stains and assays (Oil Red O, Alizarin Red, matrigel tube formation).
• Gene and protein expression of differentiation markers and TNF-α were evaluated via quantitative PCR, immunostaining, and Western blot.

Main Results:

• hASCs exhibited higher sensitivity to paclitaxel compared to fibroblasts.
• Paclitaxel significantly inhibited hASC proliferation and induced growth arrest.
• Paclitaxel markedly reduced DNA synthesis and induced apoptosis in hASCs.
• Paclitaxel severely impaired endothelial differentiation and capillary-like tube formation, decreasing key endothelial markers.
• Paclitaxel treatment led to increased TNF-α expression in hASCs.

Conclusions:

• Paclitaxel is cytotoxic to hASCs and inhibits their proliferation and differentiation.
• Paclitaxel induces apoptosis in hASCs, potentially via the TNF-α pathway.
• The observed inhibition of endothelial differentiation by paclitaxel suggests a disruption of neovascularization, likely contributing to poor wound healing in cancer patients receiving this chemotherapy.