Mesenchymal stromal cells and their derivatives – putative therapeutics in the management of autoimmune pancreatitis

Abstract

Autoimmune pancreatitis, a derivative of chronic pancreatitis, frequently causes acute episodes with clinical symptoms parallel to those of acute pancreatitis. Corticosteroids are effective in the treatment of 90% of autoimmune pancreatitis cases, but for the remaining 10%, options are limited. Due to their significant immunomodulatory capabilities, mesenchymal stromal cells (MSCs) have been proposed as a novel treatment strategy for various immune and inflammatory pathologies including those with autoimmune origins. Here, we not only highlight the most recent MSC live‐cell experiments to address acute pancreatitis, but also discuss the opportunities afforded by the emergence of the newly identified field of MSC necrobiology. We conclude that the putative employment of MSC derivatives provides a newer and simpler therapeutic approach that could have significant advantages over the use of cells themselves.

Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine

“…Necrobiology is a term used to describe the life processes associated with morphological, biochemical, and molecular changes related to cell death and the consequences and tissue response to cell death [56]. It encompasses four mechanisms by which derivatives of MSCs can retain significant clinical efficacy, including apoptosis, autophagy, mitochondrial transfer, and extracellular vesicle production [57]. The bioactive parts of dead or dying MSCs can trigger immunomodulatory properties in the host without the concern over cell survival and the formation of large aggregates [58][59][60].…”

Comparing the Therapeutic Potential of Mesenchymal Stem Cells- Derived Microvesicles and Infliximab in Chronic Pancreatitis Induced in Rats (Histological and Biochemical Study)

“…EVs were found to promote mitochondrial transfer to the macrophages increasing their phagocytic capacity and inducing an anti-inflammatory response [55] . Therefore, the recent emergence of a variety of methods to produce MSC derivatives provides a newer and simpler approach that could have significant advantages over the use of cells themselves including simpler production, lower regulatory barriers, and easier systemic transport upon intravenous delivery [11] .…”

“…Recently, not only the MSC live-cell experiments are highlighted, but also the opportunities afforded by the emergence of the newly identified field of MSC necrobiology or derivatives (MSC-derived microvesicles or MSC-MVs). The putative employment of MSC derivatives provides a newer and simpler therapeutic approach that may have significant advantages over the use of cells themselves [11] .…”

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

“…Indeed, although results have yet to be released, a clinical trial is underway examining the therapeutic effect of MSC-derived EVs in the autoimmune disease Type I diabetes (NCT02138331). Pre-clinical success in the treatment of sepsis ( Song et al, 2017 ), inflammatory bowel disease ( Yang et al, 2015 ; Mao et al, 2017 ), and multiple sclerosis ( Casella et al, 2018 ; Laso-Garcia et al, 2018 ) suggests EV-mediated treatment of inflammatory and autoimmune disorders ( Coakley et al, 2017 ; Sharma et al, 2017 ; Fujita et al, 2018 ; Xu H. et al, 2019 ; Goodman and Davies, 2020 ; Kahmini and Shahgaldi, 2020 ; Xu et al, 2020 ; Horst et al, 2021 ) may soon expand further into patient trials.…”