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Cardiometabolic diseases and cancer are among the most common diseases worldwide and are a serious concern to the healthcare system. These conditions, apparently distant, share common molecular and cellular determinants, that can represent targets for preventive and therapeutic approaches. The bone marrow plays an important role in this context as it is the main source of cells involved in cardiovascular regeneration, and one of the main sites of liquid and solid tumor metastasis, both characterized by the cellular trafficking across the bone marrow vasculature. The bone marrow vasculature has been widely studied in animal models, however, it is clear the need for human-specific in vitro models, that resemble the bone vasculature lined by endothelial cells to study the molecular mechanisms governing cell trafficking. In this review, we summarized the current knowledge on in vitro models of bone marrow vasculature developed for cardiovascular and cancer research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Campanile, Bettinelli, Cerutti and Spinetti.)

Intimal hyperplasia is the leading cause of graft failure in aortocoronary bypass grafts performed using human saphenous vein (SV). The long-term consequences of the altered pulsatile stress on the cells that populate the vein wall remains elusive, particularly the effects on saphenous vein progenitors (SVPs), cells resident in the vein adventitia with a relatively wide differentiation capacity. In the present study, we performed global transcriptomic profiling of SVPs undergoing uniaxial cyclic strain in vitro . This type of mechanical stimulation is indeed involved in the pathology of the SV. Results showed a consistent stretch-dependent gene regulation in cyclically strained SVPs vs. controls, especially at 72 h. We also observed a robust mechanically related overexpression of Adhesion Molecule with Ig Like Domain 2 (AMIGO2), a cell surface type I transmembrane protein involved in cell adhesion. The overexpression of AMIGO2 in stretched SVPs was associated with the activation of the transforming growth factor β pathway and modulation of intercellular signaling, cell-cell, and cell-matrix interactions. Moreover, the increased number of cells expressing AMIGO2 detected in porcine SV adventitia using an in vivo arterialization model confirms the upregulation of AMIGO2 protein by the arterial-like environment. These results show that mechanical stress promotes SVPs' molecular phenotypic switching and increases their responsiveness to extracellular environment alterations, thus prompting the targeting of new molecular effectors to improve the outcome of bypass graft procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maselli, Garoffolo, Cassanmagnago, Vono, Ruiter, Thomas, Madeddu, Pesce and Spinetti.)

Cardiovascular regenerative medicine is an exciting new approach that promises to change the current care of million people world-wide. Major emphasis was given to the quality and quantities of regenerative products, but recent evidence points to the importance of a better specification of the target population that may take advantage of these advanced medical treatments. Patient stratification is an important step in drug development. Tailoring treatment to the patient's specificity allowed significant improvement in cancer therapy, but personalized regenerative medicine is still at the initial stage in the cardiovascular field. For example, new-borns with a congenital heart condition and elderly people require dedicated therapeutic approaches, which adapt to their lifetime needs. In these people, personalized treatments may overcome the benefits delivered by standard protocols. In this review, we provide insights into these extreme stages of life as potential targets for cardiovascular reconstitution., (Copyright © 2019 Madeddu, Avolio, Alvino, Santopaolo and Spinetti.)