Abstract
Adipose-derived stem cells (ASCs) represent a promising tool for soft tissue engineering as well as for clinical treatment of inflammatory and autoimmune pathologies. The well-characterized multi-differentiation potential and self-renewal properties of ASCs are coupled with their immunomodulatory ability in providing therapeutic efficacy. Yet, their impact in immune or inflammatory disorders might rely both on cell contact-dependent mechanisms and paracrine effects, resulting in the release of various soluble factors that regulate immune cells functions. Despite the widespread use of ASCs in clinical trials addressing several pathologies, the pathophysiological mechanisms at the basis of their clinical use have been not yet fully investigated. In particular, a thorough analysis of ASC immunomodulatory potential is mandatory. Here we explore such molecular mechanisms involved in ASC immunomodulatory properties, emphasizing the relevance of the milieu composition. We review the potential clinical use of ASC secretome as a mediator for immunomodulation, with a focus on in vitro and in vivo environmental conditions affecting clinical outcome. We describe some potential strategies for optimization of ASCs immunomodulatory capacity in clinical settings, which act either on adult stem cells gene expression and local microenvironment. Finally, we discuss the limitations of both allogeneic and autologous ASC use, highlighting the issues to be fixed in order to significantly improve the efficacy of ASC-based cell therapy.
Highlights
Adipose-derived mesenchymal stem cells (ASCs) represent a population of self-renewing multipotent adult cells in the vascular stroma of adipose tissues, playing important roles in development, post-natal growth, maintenance of tissue homeostasis and tissue repair and regeneration (Shingyochi et al, 2015; Dai et al, 2016)
Significant amount of ASCs can be readily accessible from subcutaneous liposuction and, when appropriately stimulated, they can further differentiate into several cell-like types, including adipocytes, osteocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic cells, and hepatocytes (Zuk et al, 2001, 2002; PlanatBénard et al, 2004; Aurich et al, 2009; Dave et al, 2014; Sommese et al, 2017)
ASCs primed with IL-17, tumor necrosis factor α (TNF-α), and IFN-γ have increased T cell immunosuppressive capacity mediated by inducible nitric oxide synthase production and have been shown to reduce inflammation and tissue injury in murine model of hepatitis (Han et al, 2014)
Summary
Adipose-derived mesenchymal stem cells (ASCs) represent a population of self-renewing multipotent adult cells in the vascular stroma of adipose tissues, playing important roles in development, post-natal growth, maintenance of tissue homeostasis and tissue repair and regeneration (Shingyochi et al, 2015; Dai et al, 2016). ASC-based cellular therapy has been further considered for the treatment of neurodegenerative diseases, including mouse models of Alzheimer’s disease or Parkinson’s disease and amyotrophic lateral sclerosis (ALS) patients (McCoy et al, 2008; Yan et al, 2014; Fontanilla et al, 2015; Staff et al, 2016), as well as, in humans, for immunological disorders, such as graft versus host disease (GvHD) (Yañez et al, 2006; Fang et al, 2007; Tholpady et al, 2009) and autoimmune pathologies, such as type I diabetes mellitus (Vanikar et al, 2010; Lin et al, 2015), systemic sclerosis (Scuderi et al, 2013), rheumatoid arthritis (El-Jawhari et al, 2014; Ueyama et al, 2020) and systemic lupus erythematosus (SLE) (Liang et al, 2010; Park et al, 2015).
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