Abstract
Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.
Highlights
Immune-mediated inflammatory diseases (IMIDs) are pathological conditions characterized by defective immune responses that lead to chronic tissue damage [1]
Among the soluble factors secreted by the anti-inflammatory MSC2 phenotype, it is possible to find a plethora of molecules including growth factors, cytokines and enzymes
Despite numerous studies showing that the immunomodulatory effects of mesenchymal stromal cells (MSCs) are promising in inflammation management, the cell-based therapies present important limitations
Summary
Immune-mediated inflammatory diseases (IMIDs) are pathological conditions characterized by defective immune responses that lead to chronic tissue damage [1]. Intravenous administration of human MSCs is generally accepted as safe, only showing postinfusion febrile and site reactions, the likelihood of more severe side effects such as thrombosis or adverse inflammatory effects is still present [18,22,27,29,30] Another obstacle for the clinical translation of cell-based therapies is that their legal regulation is complex and not well defined in some of the cases. Immunomodulatory effects on immune cells such as lymphocytes, macrophages and NK cells Because of these issues—and taking into account that the secretory effects of MSCs. MSCs[27,28]—the is generally are considered main factor responsible their therapeutic properties accepted has as safe, showing postinfusion secretome, febrile andwhich site reactions, the likelihood of attention only shifted to the MSC-derived will be deeply reviewed in more severe side as thrombosis or adverse is still present
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