Toward transplantation tolerance with adipose tissue-derived therapeutics

Abstract

Solid organ and composite tissue allotransplanation have been widely applied to treat end-stage organ failure and massive tissue defects, respectively. Currently there are a lot of research endeavors focusing on induction of transplantation tolerance, to relieve the burden derived from long-term immunosuppressant uptake. The mesenchymal stromal cells (MSCs) have been demonstrated with potent immunomodulatory capacities and applied as promising cellular therapeutics to promote allograft survival and induce tolerance. As a rich source of adult MSCs, adipose tissue provides additional advantages of easy accessibility and good safety profile. In recent years, the stromal vascular fraction (SVF) isolated from adipose tissues following enzymatic or mechanical processing without in vitro culture and expansion has demonstrated immunomodulatory and proangiogenic properties. Furthermore, the secretome of AD-MSCs has been utilized in transplantation field as a potential “cell-free” therapeutics. This article reviews recent studies that employ these adipose-derived therapeutics, including AD-MSCs, SVF, and secretome, in various aspects of organ and tissue allotransplantation. Most reports validate their efficacies in prolonging allograft survival. Specifically, the SVF and secretome have performed well for graft preservation and pretreatment, potentially through their proangiogenic and antioxidative capacities. In contrast, AD-MSCs were suitable for peri-transplantation immunosuppression. The proper combination of AD-MSCs, lymphodepletion and conventional immunosuppressants could consistently induce donor-specific tolerance to vascularized composite allotransplants (VCA). For each type of transplantation, optimizing the choice of therapeutics, timing, dose, and frequency of administration may be required. Future progress in the application of adipose-derived therapeutics to induce transplantation tolerance will be further benefited by continued research into their mechanisms of action and the development of standardized protocols for isolation methodologies, cell culture, and efficacy evaluation.

Effect of Inflammatory Microenvironment on the Regenerative Capacity of Adipose-Derived Mesenchymal Stem Cells

“…In these diseases, AD-MSCs must regenerate tissues in a highly inflamed environment, which affects their expression profile. These experiments reflect the changes in gene and protein expression of AD-MSCs after exposure to inflammation agents [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

Licensing effects of inflammatory factors and TLR ligands on the regenerative capacity of adipose-derived mesenchymal stem cells

“…The role of adipose-derived mesenchymal stem cells (AD-MSCs) in wound healing is a subject of considerable significance. These cells exhibit a wide array of regenerative, anti-apoptotic, antifibrotic, anti-oxidative, and immunomodulatory properties, rendering them invaluable for therapeutic applications, particularly in wound healing ( Neuss et al, 2004 ; Fu et al, 2009 ; DelaRosa and Lombardo, 2010 ; Trayhurn et al, 2011 ; Shohara et al, 2012 ; Konno et al, 2013 ; Cao et al, 2015 ; Ti et al, 2015 ; Furuta et al, 2016 ; Carelli et al, 2018 ; Feldbrin et al, 2018 ; Mushahary et al, 2018 ; Ridiandries et al, 2018 ; Sahu et al, 2019 ; Al-Ghadban and Bunnell, 2020 ; Kuca-Warnawin et al, 2020 ; Kurte et al, 2020 ; Munir et al, 2020 ; Xiao et al, 2020 ; Bunnell BA, 2021 ; Krampera and Le Blanc, 2021 ; Nieto-Nicolau et al, 2021 ; Krawczenko and Klimczak, 2022 ; Skibber et al, 2022 ; Wiese et al, 2022 ; Cheng et al, 2023 ; Huerta et al, 2023 ).…”

“…These versatile cells offer a means to restore tissue function effectively and safely. To ensure secure and successful application in AD-MSC-based therapies, the purity and potency of these cells must be rigorously assessed before administration ( Fu et al, 2009 ; DelaRosa and Lombardo, 2010 ; Anton et al, 2012 ; François et al, 2012 ; Shohara et al, 2012 ; Konno et al, 2013 ; Cao et al, 2015 ; Furuta et al, 2016 ; Li and Hua, 2017 ; Carelli et al, 2018 ; Feldbrin et al, 2018 ; Guasti et al, 2018 ; Mushahary et al, 2018 ; Qi et al, 2018 ; Ridiandries et al, 2018 ; Zwick et al, 2018 ; Pittenger et al, 2019 ; Sahu et al, 2019 ; Al-Ghadban and Bunnell, 2020 ; Kuca-Warnawin et al, 2020 ; Kurte et al, 2020 ; Mazini et al, 2020 ; Munir et al, 2020 ; Song et al, 2020 ; Xiao et al, 2020 ; Bunnell BA, 2021 ; Krampera and Le Blanc, 2021 ; Nieto-Nicolau et al, 2021 ; Krawczenko and Klimczak, 2022 ; Cheng et al, 2023 ; Huerta et al, 2023 ; Szucs et al, 2023 ).…”

Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells by Hydrogel Encapsulation

“…This approach holds promise for other immune-related conditions, including organ or tissue allotransplantation. MSCs have shown potential to induce donor-specific tolerance in allotransplantation settings [153,154], and future studies incorporating hydrogel and MSCs may alleviate patients from the burden of life-long immunosuppressants.…”