BACKGROUND: Mononuclear cells contain progenitor cells including haematopoietic and mesenchymal stem cells, endothelial progenitor cells and fibroblasts which facilitate wound healing through cytokines, growth factor secretions, cell-cell interactions and provision of extracellular matrix scaffolding. Clinical applications of autologous mononuclear cells therapy in wound healing in non-malignant patients with critical limb ischaemia have been reported with remarkable outcome.
METHODS: We report three patients with haematological malignancies undergoing chemotherapy, who received autologous mononuclear cells implantation to treat non-healing wound after optimum conventional wound care. The sources of mononuclear cells (MNC) were from bone marrow (BM), peripheral blood (PB) and mobilised PB cells (mPB-MNC) using granulocyte colony stimulating factor (G-CSF). The cells were directly implanted into wound and below epidermis. Wound sizes and adverse effects from implantation were assessed at regular intervals.
RESULTS: All patients achieved wound healing within three months following autologous mononuclear cells implantation. No implantation adverse effects were observed.
CONCLUSIONS: Autologous mononuclear cells therapy is a feasible alternative to conventional wound care to promote complete healing in non-healing wounds compounded by morbid factors such as haematological malignancies, chemotherapy, diabetes mellitus (DM), infections and prolonged immobility.
BACKGROUND: The mainstay of treatment for carbuncles involves the early administration of antibiotics in combination with surgical intervention. The conventional saucerisation, or incision and drainage, under normal circumstances results in moderate to large wounds, which may need secondary surgery such as skin grafting, resulting in a longer duration of wound healing and jeopardising cosmetic outcome.
CASE REPORTS: The reported three cases presented with extensive carbuncles over the chin, face and lips region. In addition to early commencement of intravenous antibiotics, the pus was drained, with minimal incision and conservative wound debridement, with the aim of maximal skin conservation. This was followed by thrice-daily irrigation with antibiotic-containing solution for a minimum of 2 consecutive days. The wounds healed within two to four weeks, without major cosmetic compromise.
CONCLUSION: The new method showed superior cosmetic outcomes, with a shorter duration of wound healing. Conservative surgical management can be performed under regional anaesthesia, which may reduce morbidity and mortality; patients with facial carbuncles often have higher risks with general anaesthesia.
METHODS: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29.
RESULTS: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3.
CONCLUSIONS: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.