Deciphering the Heterogeneity Landscape of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Precise Selection in Translational Medicine.

Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have been considered promising therapeutics for disease treatments. However, MSC-EVs harvested from different tissues present unique biological features reflective of their origins. The heterogeneity of MSC-EVs constitutes an important barrier to their precise application in clinical translation that may probably lead to uncertain therapeutic effects. To give hints for future clinical translation, five MSCs are employed, whose derived EVs are most intensively utilized, namely bone marrow mesenchymal stem/stromal cells (BMMSCs), umbilical cord stem/stromal cells (UCSCs), adipose-derived stem/stromal cells (ASCs), dermal stem/stromal cells (DSCs) and dental pulp stem/stromal cells (DPSCs) and the heterogeneity landscape of the corresponding MSC-EVs are documented. Overall, the basic parameters, stability, and biosafety of different MSC-EVs are indiscriminate. Strikingly, UCSC-EVs exhibit distinguishing productivity. UCSC-EVs as well as DPSC-EVs present better drug loading/delivery capacity. In addition, the heterogeneity of different MSC-EVs in cargo diversity, cellular affinity, organ biodistribution, and therapeutic effects may cue the rational selection in different disease treatments. Through a combined assessment, a rational strategy is combined for selecting MSC-EVs in future clinics. Offering a panoramic view of MSC-EVs harvested from different tissues, the current study may provide guidelines for the precise selection of MSC-EVs in next-generation therapeutics.

[Finite element analysis of first maxillary molars restored with different post and core materials].

PURPOSE: To analyze the stress magnitude and distribution of residual dentin in maxillary first molar restored with post and crown using three-dimension finite element methods. METHODS: An intact maxillary first molar was scanned using a 3DX multi-image micro-CT. Three-dimensional finite element models simulated an endodontically treated first maxillary molar restored with post and crown, which were varied in different number and material of post. A load of 480 N, simulating intercuspal occlusion, was applied vertically to the occlusal surface and a load of 240 N simulating mastication was applied to the occlusal surface with a 45° angle to the long axis of the tooth. Von Mises stresses were calculated by MSC.Marc software. RESULTS: The maximum stresses among the post in the radicular portion increased as elastic modulus of the material increased. The stress values of remaining dentin observed in two-post group were lower than those in one post group and three-post group for cast metal post systems. In the test simulating mastication, the peak value of Von Mises stress was higher on remaining dentin among the post in the radicular portion and lower on the outer surface of residual tooth tissue than that in the test simulating intercuspal occlusion. CONCLUSIONS: The number, material of post and occlusal loading have influence on magnitude and distributionn of stress. Supported by Natural Science Foundation of China (81271175) and National Science and Technology Supporting Plan (2012BAI07B01).