Stem cell-derived exosomes for wound healing: current status and promising directions.

Wound healing, especially of chronic wounds, is still an unmet therapeutic area since assessment and management are extremely complicated. Although many efforts have been made to treat wounds, all strategies have achieved limited results for chronic wounds. Stem cell-based therapy is considered a promising approach for complex wounds such as those occurring in diabetics. Mesenchymal stem cell transplantation significantly improves wound closure, angiogenesis and wound healing. However, cell therapy is complex, expensive and time-consuming. Recent studies have shown that stem cell-derived exosomes can be an exciting approach to treat wounds. Exosomes derived from mesenchymal stem cells can induce benefit in almost all stages of wound healing, including control of immune responses, inhibition of inflammation, promoting cell proliferation and angiogenesis, while reducing scar formation during the wound healing process. This review aimed at offering an updated overview of the use of exosomes in biological applications, such as wound healing, and addresses not only current applications but also new directions for this next-generation approach in wound healing.

Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy.

BACKGROUND: Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs). METHODS: We isolated a breast cancer cell population (CD44+CD24- cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. RESULTS: Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. CONCLUSIONS: Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.