Topically Delivered Adipose Derived Stem Cells Show an Activated-Fibroblast Phenotype and Enhance Granulation Tissue Formation in Skin Wounds

Seok Jong Hong,Ping Xie,Kai P Leung,Wei Xu,Thomas A Mustoe,Robert D Galiano,Sheng-Xian Jia,Leonard Eisenberg

doi:10.1371/journal.pone.0055640

Abstract

Multipotent mesenchymal stem cells (MSCs) are found in various tissues and can proliferate extensively in vitro. MSCs have been used in preclinical animal studies and clinical trials in many fields. Adipose derived stem cells (ASCs) have several advantages compared to other MSCs for use in cell-based treatments because they are easy to isolate with relative abundance. However, quantitative approaches for wound repair using ASCs have been limited because of lack of animal models which allow for quantification. Here, we addressed the effect of topically delivered ASCs in wound repair by quantitative analysis using the rabbit ear model. We characterized rabbit ASCs, and analyzed their multipotency in comparison to bone marrow derived-MSCs (BM-MSCs) and dermal fibroblasts (DFs) in vitro. Topically delivered ASCs increased granulation tissue formation in wounds when compared to saline controls, whereas BM-MSCs or DFs did not. These studies suggest that ASCs and BM-MSCs are not identical, though they have similar surface markers. We found that topically delivered ASCs are engrafted and proliferate in the wounds. We showed that transplanted ASCs exhibited activated fibroblast phenotype, increased endothelial cell recruitment, and enhanced macrophage recruitment in vivo.

Highlights

Wound repair is a complex and dynamic process which consists of inflammation, angiogenesis, and tissue formation and remodeling [1,2,3]
Rabbit BM-mesenchymal stem cells (MSCs) have a larger surface area compared to Adipose derived stem cells (ASCs) (Figure 1B)
Expression of CD29, CD44, CD90, and CD105 was detected without significant changes, though minor variations were found when quantified with the NIH ImageJ program, from passage 1 through passage 9 both in ASCs (Figure 1D) and BMMSCs (Figure S1)

Summary

Introduction

Wound repair is a complex and dynamic process which consists of inflammation, angiogenesis, and tissue formation and remodeling [1,2,3]. Circulating platelets migrate to the wound and release inflammatory signals such as transforming growth factor-b (TGF-b), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF). This is followed by the infiltration of neutrophils and macrophages and the migration of keratinocytes to the wound to recover the barrier function of skin. Endothelial cells and fibroblasts migrate to the site and build up granulation tissues by depositing collagen and other extracellular matrices. Wound repair is a highly orchestrated sequential process in which signals of one cell type regulate other cell types in a cascade

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