Elsevier

Cellular Immunology

Volume 278, Issues 1–2, July–August 2012, Pages 152-157
Cellular Immunology

Adipose-derived stem cells induced dendritic cells undergo tolerance and inhibit Th1 polarization

https://doi.org/10.1016/j.cellimm.2012.07.008Get rights and content

Abstract

Adipose tissue-derived stem cells (ADSC) have been shown to possess stem cell properties such as transdifferentiation, self-renewal and therapeutic potential. However, the property of ADSC to accommodate immune system is still unknown. In this study, ADSC were cocultured with allogenetic dendritic cells (DC), and then treated DC were mixed with allogenetic CD4+ T cells. The results demonstrated that ADSC could downregulate costimulatory molecules, including CD80, CD83, CD86, and cytokine secretion such as interleukin (IL)-12 and tumor necrosis factor (TNF)-α, while upregulate indoleamine-2,3-dioxygenase (IDO) of allogenetic DC. In addition, treated DC could inhibit CD4+ Tcell activation and naïve T cells toward Th1 polarization.

The results suggest that ADSC could negatively modulate immunity and induce immune tolerance, which provide a promising strategy in transplantation or autoimmune disease.

Highlights

ADSC could downregulate costimulatory molecules and cytokine secretion of allogenetic DC. ► Treated DC could inhibit CD4+ T cell activation and naïve T cells toward Th1 polarization. ► ADSC could negatively modulate immunity and induce immune tolerance.

Introduction

Adipose-derived stem cells (ADSC) are able to differentiate into the classical mesodermal tissues like bone, fat, nerve, cardiomyocytes, hepatocytes and pancreatic cells [1], [2], [3], [4]. Therefore, they represent a promising source for cell therapy, especially as their isolation is less invasive compared to bone marrow extractions and their expansion in culture is quite easy [5], [6], [7].

In addition, stem-cell transplantation has emerged as a new treatment modality for patients with refractory, severe autoimmune disease [8], [9], [10]. Its rationale is based on eliminating autoaggressive lymphocytes by lympho- or myeloablative conditioning followed by stem-cell rescue [11], [12], [13]. Preclinical studies in animal models of autoimmune disease and observations in patients with rheumatoid arthritis (RA) who were cured after allogeneic bone marrow transplantation for concomitant hematologic malignancy have provided support for the concept [14], [15], [16].

However, the immune property of ADSC is still unknown. We wondered whether ADSC could also modulate immune response, To identify it, we isolated ADSC from human fat tissue, and explored its immune function. The results demonstrated that ADSC could negatively modulate immunity and induce immune tolerance by regulating DC.

Section snippets

Preparation of ADSC

In brief, the subcutaneous adipose tissue was dissected from omental fat who underwent abdominal surgery. The volunteer were healthy with the age of 30–50 years. The isolated adipose tissue was washed extensively with phosphate-buffered saline (PBS) to remove contaminating debris and blood cells. The 50 mL adipose tissue was minced and digested with 50 mL collagenase I (2 mg/mL; Worthington Biochemical) at 37 °C for 30 min. Collagenase activity was neutralized by DMEM-F12 (HyClone) containing 15%

Morphologic and phenotypic characteristics of of ADSC

At 24 h of primary culture in medium containing 10% fetal bovine serum, ADSC adhered to the culture dish sparsely and the majority of cells displayed a spindle-like shape. As shown in Fig. 1A, after 14 days, ADSCs commonly achieved 80% confluence with a rather homogeneous population of fibroblast-like morphology. In addition, as shown in Fig. 1B, flow cytometric analysis showed that the ADSC expressed high level of CD29, CD44 and CD105. These results revealed that cultured ADSC were homogeneous

Discussion

Soft-tissue loss presents an ongoing challenge in plastic and reconstructive surgery [17], [18]. Standard approaches to soft-tissue reconstruction include autologous tissue flaps, autologous fat transplantation and alloplastic implants [19], [20], [21]. All of these approaches have disadvantages, including donor-site morbidity, implant migration and absorption and foreign body reaction [22], [23], [24]. Stem cell application has recently been suggested as a possible novel therapy [25], [26],

Acknowledgment

This work was supported by 2011CB964701 of China.

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