Background: Cell-based therapy products are supposed to be the most complex medicine products in the history of human medical care. In this study, we established a safety evaluation system for therapeutic stromal cells based on the existing regulations and current testing techniques to provide general quality requirements for human umbilical cord mesenchymal stromal cell (HUCMSC) therapy product. Methods: In this system, we comprehensively evaluate the environmental monitoring program, quality control of critical raw materials and reagents, donor screening criteria, cell safety, quality, and biological effects, not only in line with the basic criteria of biological products, but also following the general requirements of drugs. Results: The qualified HUCMSCs were tested for various clinical researches in our hospital, and no severe adverse reaction was observed in 225 patients during a 1-year follow-up period. Conclusion: In this study, we establish a systemic quality control and potent assays to guarantee the safety and effectiveness of HUCMSCs based on a minimum set of standards in MSC-based product.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with poor prognosis. And different individuals respond to the same drug differently. Increasing evidence has confirmed that metabolism reprogramming was involved in the drug sensitivity of tumor cells. However, the potential molecular mechanism of 5‐fluorouracil (5‐FU) sensitivity remains to be elucidated in ESCC cells. In this study, we found that the 5‐FU sensitivity of TE1 cells was lower than that of EC1 and Eca109 cells. Gas chromatography‐mass spectrometry analysis results showed that nicotinate and nicotinamide metabolism and tricarboxylic acid cycle were significantly different in these three cell lines. Nicotinamide N‐methyltransferase (NNMT), a key enzyme of nicotinate and nicotinamide metabolism, was significantly higher expressed in TE1 cells than that in EC1 and Eca109 cells. Therefore, the function of NNMT on 5‐FU sensitivity was analyzed in vitro and in vivo. NNMT downregulation significantly increased 5‐FU sensitivity in TE1 cells. Meanwhile, the glucose consumption and lactate production were decreased, and the expression of glycolysis‐related enzymes hexokinase 2, lactate dehydrogenase A, and phosphoglycerate mutase 1 were downregulated in NNMT knockdown TE1 cells. Besides, overexpression of NNMT in EC1 and Eca109 cells caused the opposite effects. Moreover, when glycolysis was inhibited by 2‐deoxyglucose, the roles of NNMT on 5‐FU sensitivity was weakened. In vivo experiments showed that NNMT knockdown significantly increased the sensitivity of xenografts to 5‐FU and suppressed the Warburg effect. Overall, these results demonstrated that NNMT decreases 5‐FU sensitivity in human ESCC cells through promoting the Warburg effect, suggesting that NNMT may contribute to predict the treatment effects of the clinical chemotherapy in ESCC.

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Mesenchymal stem cells (MSCs) are promising candidates for skin wound repair due to their capabilities of accumulating at wounds and differentiating into multiple types of skin cells. However, the underlying mechanisms responsible for these processes remain unclear. In this study, we found that osteopontin (OPN) stimulated the migration of MSCs in vitro, and observed the recruitment of endogenous MSCs to a skin wound and their differentiation into keratinocytes and endothelial cells. In OPN knock-out mice, the recruitment of MSCs to the skin wound was significantly inhibited, and wound closure was hampered after an intradermal injection of exogenous MSCs compared to wild-type mice. Consistent with these observations, the expressions of adhesion molecule CD44 and its receptor E-selectin were significantly decreased in the lesions of OPN knock-out mice compared with wild-type mice suggesting that OPN may regulate the migration of MSCs through its interactions with CD44 during skin wound recovery. In summary, our data demonstrated that OPN played a critical role in activating the migration of MSCs to injured sites and their differentiation into specific skin cell types during skin wound healing.

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