Cell therapy in the cornea: The emerging role of microenvironment.

The cornea is an ideal testing field for cell therapies. Its highly ordered structure, where specific cell populations are sequestered in different layers, together with its accessibility, has allowed the development of the first stem cell-based therapy approved by the European Medicine Agency. Today, different techniques have been proposed for autologous and allogeneic limbal and non-limbal cell transplantation. Cell replacement has also been attempted in cases of endothelial cell decompensation as it occurs in Fuchs dystrophy: injection of cultivated allogeneic endothelial cells is now in advanced phases of clinical development. Recently, stromal substitutes have been developed with excellent integration capability and transparency. Finally, cell-derived products, such as exosomes obtained from different sources, have been investigated for the treatment of severe corneal diseases with encouraging results. Optimization of the success rate of cell therapies obviously requires high-quality cultured cells/products, but the role of the surrounding microenvironment is equally important to allow engraftment of transplanted cells, to preserve their functions and, ultimately, lead to restoration of tissue integrity and transparency of the cornea.

Validation of airway porcine epithelial cells as an alternative to human in vitro preclinical studies.

Animal models are currently used in several fields of biomedical research as useful alternatives to human-based studies. However, the obtained results do not always effectively translate into clinical applications, due to interspecies anatomical and physiological differences. Detailed comparability studies are therefore required to verify whether the selected animal species could be a representative model for the disease or for cellular process under investigation. This has proven to be fundamental to obtaining reliable data from preclinical studies. Among the different species, swine is deemed an excellent animal model in many fields of biological research, and has been largely used in respiratory medicine, considering the high homology between human and swine airways. In the context of in vitro studies, the validation of porcine airway epithelial cells as an alternative to human epithelial cells is crucial. In this paper, porcine and human tracheal and bronchial epithelial cells are compared in terms of in vivo tissue architecture and in vitro cell behaviour under standard and airlifted conditions, analyzing the regenerative, proliferative and differentiative potentials of these cells. We report multiple analogies between the two species, validating the employment of porcine airway epithelial cells for most in vitro preclinical studies, although with some limitations due to species-related divergences.

The Growing Medical Need for Tracheal Replacement: Reconstructive Strategies Should Overcome Their Limits.

Breathing, being predominantly an automatic action, is often taken for granted. However, respiratory diseases affect millions of people globally, emerging as one of the major causes of disability and death overall. Among the respiratory dysfunctions, tracheal alterations have always represented a primary challenge for clinicians, biologists, and engineers. Indeed, in the case of wide structural alterations involving more than 50% of the tracheal length in adults or 30% in children, the available medical treatments are ineffective or inapplicable. So far, a plethora of reconstructive approaches have been proposed and clinically applied to face this growing, unmet medical need. Unfortunately, none of them has become a well-established and routinely applied clinical procedure to date. This review summarizes the main clinical reconstructive attempts and classifies them as non-tissue engineering and tissue engineering strategies. The analysis of the achievements and the main difficulties that still hinder this field, together with the evaluation of the forefront preclinical experiences in tracheal repair/replacement, is functional to promote a safer and more effective clinical translation in the near future.

Regenerative Medicine of Epithelia: Lessons From the Past and Future Goals.

This article explores examples of successful and unsuccessful regenerative medicine on human epithelia. To evaluate the applications of the first regenerated tissues, the analysis of the past successes and failures addresses some pending issues and lay the groundwork for developing new therapies. Research should still be encouraged to fill the gap between pathologies, clinical applications and what regenerative medicine can attain with current knowledge.