Human Mesenchymal Stem Cells (hMSCs) play an important role as new therapeutic alternatives in advanced therapies and regenerative medicine thanks to their regenerative and immunomodulatory properties, and ability to migrate to the exact area of injury. These properties have made hMSCs one of the more promising cellular active substances at present, particularly in terms of the development of new and innovative hMSC-based products. Currently, numerous clinical trials are being conducted to evaluate the therapeutic activity of hMSC-based products on specific targets. Given the rapidly growing number of hMSC clinical trials in recent years and the complexity of these products due to their cellular component characteristics and medicinal product status, there is a greater need to define more stringent, specific, and harmonized requirements to characterize the quality of the hMSCs and enhance the analysis of their safety and efficacy in final products to be administered to patients. These requirements should be implemented throughout the manufacturing process to guarantee the function and integrity of hMSCs and to ensure that the hMSC-based final product consistently meets its specifications across batches. This paper describes the principal phases involved in the design of the manufacturing process and updates the specific technical requirements needed to address the appropriate clinical use of hMSC-based products. The challenges and limitations to evaluating the safety, efficacy, and quality of hMSCs have been also reviewed and discussed.

Proepicardial/epicardial‐derived cells are the main origin of the early embryonic coronary vascular bed. In vivo coronary vasculogenesis, which is a fast‐occurring event, can be mimicked in vitro by culturing proepicardial tissue in different ways. The in vitro vasculogenic model presented in this study (a proepicardial suspension culture assay) partially reproduces coronary vascular development from its cellular precursors, a process known to be highly dependent on cell migration, cell differentiation, cell adhesion/sorting, and tissue fusion phenomena. The main aim of this study is to study the triggering signals and the cellular dynamics that regulate the differentiation of proepicardial cells into the angioblastic/endothelial lineage and their in vitro vasculogenic potential. Our results indicate that hanging drop‐cultured proepicardia, which have an intrinsic vascular potential, behave like self‐assembling cell aggregates or spheroids that can fuse to give rise to complex vascularized 3D structures. We believe that these self‐assembling cell aggregates are an optimal choice to study the differentiation of coronary angioblasts, as well as a good method to reproduce vascular development in vitro. Finally, we propose the proepicardium as a suitable cellular source for vascular tissue engineering. Anat Rec Part A, 288A:700–713, 2006.

Cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) hold a great potential as human in vitro models for studying heart disease and for drug safety screening. Nevertheless, their associated immaturity relative to the adult myocardium limits their utility in cardiac research. In this study, we describe the development of a platform for generating three-dimensional engineered heart tissues (EHTs) from hPSC-CMs for the measurement of force while under mechanical and electrical stimulation. The modular and versatile EHT platform presented here allows for the formation of three tissues per well in a 12-well plate format, resulting in 36 tissues per plate. We compared the functional performance of EHTs and their histology in three different media and demonstrated that tissues cultured and maintained in maturation medium, containing triiodothyronine (T3), dexamethasone, and insulin-like growth factor-1 (TDI), resulted in a higher force of contraction, sarcomeric organization and alignment, and a higher and lower inotropic response to isoproterenol and nifedipine, respectively. Moreover, in this study, we highlight the importance of integrating a serum-free maturation medium in the EHT platform, making it a suitable tool for cardiovascular research, disease modeling, and preclinical drug testing.

We report the synthesis and comprehensive study of two chromophores based on 4H-pyranylidene moiety as a part of the π-conjugated spacer. Triphenylamine (TPA) acts as donor and tricarbonitrile-based electron-accepting groups complete these V-shaped D–A–D architectures (A, acceptor; D, donor). Their electrochemical, photophysical and nonlinear optical properties are analyzed in detail by using a joint experimental and theoretical approach. The two chromophores exhibit near-infrared fluorescence, large Stokes shift, enhanced emission in tetrahydrofuran/water mixtures and good photostability. Additionally, the dimerization of triphenylamine groups to tetraphenylbenzidine (TPB) takes place upon electrochemical and chemical oxidation showing their peculiar electrochemical behavior and film formation capabilities. Interestingly, high molecular first hyperpolarizabilities and two-photon absorption cross-sections were found, highlighting their potential applications in electro-optical devices. Overall, our work demonstrates that these near-infrared (NIR) fluorescent chromophores are versatile materials with a myriad of applications ranging from optoelectronics to biological applications.