Abstract

Macrophages and microglia represent the primary phagocytes and first line of defense in the peripheral and central immune systems. They activate and polarize into a spectrum of pro- and anti-inflammatory phenotypes in response to various stimuli. This activation is tightly regulated to balance the appropriate immune response with tissue repair and homeostasis. Disruption of this balance results in inflammatory disease states and tissue damage. Adipose stem cells (ASCs) have great therapeutic potential because of the potent immunomodulatory capabilities which induce the polarization of microglia and macrophages to the anti-inflammatory, M2, phenotype. In this study, we examined the effects of donor heterogeneity on ASC function. Specifically, we investigated the impact of donor obesity on ASC stemness and immunomodulatory abilities. Our findings revealed that ASCs from obese donors (ObASCs) exhibited reduced stem cell characteristics when compared to ASCs from lean donors (LnASCs). We also found that ObASCs promote a pro-inflammatory phenotype in murine macrophage and microglial cells, as indicated by the upregulated expression of pro-inflammatory genes, increased nitric oxide pathway activity, and impaired phagocytosis and migration. These findings highlight the importance of considering individual donor characteristics such as obesity when selecting donors and cells for use in ASC therapeutic applications and regenerative medicine.

Highlights

  • Adipose tissue-derived stem cells (ASCs), a type of mesenchymal stem cell (MSC), possess significant anti-inflammatory and immunomodulatory properties that make them an attractive therapeutic option for numerous inflammatory diseases

  • ObASCs Exhibit Reduced Stemness Characteristics When Compared with lean ASCs (LnASCs)

  • Adipose stem cells have tremendous therapeutic potential because of their remarkable ability to migrate to sites of inflammation where they recruit immune cells and orchestrate tissue repair [56,57,58]

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Summary

Introduction

Adipose tissue-derived stem cells (ASCs), a type of mesenchymal stem cell (MSC), possess significant anti-inflammatory and immunomodulatory properties that make them an attractive therapeutic option for numerous inflammatory diseases. Pre-treatment of ASCs with pro-inflammatory factors or hypoxic conditions strengthens their immunomodulatory abilities [3,5,6,7,8] These stressful conditions mimic the post-transplant tissue niche and provide some evidence for their behavior in vivo. Because of these properties, ASCs have been investigated as therapeutic agents in animal models of various diseases such as multiple sclerosis (MS) [9,10], uveitis [11,12], kidney injury [13,14], inflammatory bowel disease [15,16,17], and cutaneous wound healing [18,19]. Results from these studies suggest that ASCs possess robust immunosuppressive potential in numerous disease states; the application of ASC-based therapies to the clinic has met with limited success

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