Characterization of Dermal Stem Cells of Diabetic Patients.

Letizia Ferroni,Barbara Zavan,Gloria Bellin,Gianluca Campo,Chiara Gardin,Luca Dalla Paola,Paolo Pinton,Paolo Cimaglia

doi:10.3390/cells8070729

Letizia Ferroni, Barbara Zavan + Show 6 more

Open Access

https://doi.org/10.3390/cells8070729

Copy DOI

Journal: Cells	Publication Date: Jul 16, 2019
Citations: 20	License type: CC BY 4.0

Affiliation: Maria Cecilia Hospital, University of Ferrara

Abstract

Diabetic foot ulcers (DFUs) are lesions that involve loss of epithelium and dermis, sometimes involving deep structures, compartments, and bones. The aim of this work is to investigate the innate regenerative properties of dermal tissue around ulcers by the identification and analysis of resident dermal stem cells (DSCs). Dermal samples were taken at the edge of DFUs, and genes related to the wound healing process were analyzed by the real-time PCR array. The DSCs were isolated and analyzed by immunofluorescence, flow cytometry, and real-time PCR array to define their stemness properties. The gene expression profile of dermal tissue showed a dysregulation in growth factors, metalloproteinases, collagens, and integrins involved in the wound healing process. In the basal condition, diabetic DSCs adhered on the culture plate with spindle-shaped fibroblast-like morphology. They were positive to the mesenchymal stem cells markers CD44, CD73, CD90, and CD105, but negative for the hematopoietic markers CD14, CD34, CD45, and HLA-DR. In diabetic DSCs, the transcription of genes related to self-renewal and cell division were equivalent to that in normal DSCs. However, the expression of CCNA2, CCND2, CDK1, ALDH1A1, and ABCG2 was downregulated compared with that of normal DSCs. These genes are also related to cell cycle progression and stem cell maintenance. Further investigation will improve the understanding of the molecular mechanisms by which these genes together govern cell proliferation, revealing new strategies useful for future treatment of DFUs.

Highlights

Diabetes mellitus is a universal health problem
In order to define the molecular alterations underlying the development of chronic ulcers in diabetic patients, the expression of 84 key wound healing associated genes was probed by real-time
The present study has demonstrated that in diabetic dermal tissue around diabetic foot ulcers (DFUs) there is an impairment in the gene expression profile of growth factors, metalloproteinases, collagens, and integrins involved in the wound healing process

Summary

Introduction

Diabetes mellitus is a universal health problem. People suffering from diabetes endure long-term complications such as cardiovascular diseases, nephropathy, retinopathy, neuropathy, and ulcers in the lower limbs. Diabetic neuropathy and peripheral arterial disease are common factors that cause diabetic foot ulcers (DFUs). Motor neuropathy causes muscle weakness, atrophy, and paresis, sensory neuropathy leads to loss of the protective sensation of pain, pressure, and heat, and autonomic dysfunction causes vasodilation and decreased sweating, resulting in a loss of skin integrity, providing a site vulnerable to microbial infection [1]. 25% of patients suffering from diabetes mellitus develop during their lifetime skin ulcers below the ankle, which seriously affect their quality of life, can be limb- and life-threatening, and are responsible for the majority of hospital admissions among diabetics. DFUs constitute a major public health burden in both the developed and developing countries [2].

Objectives

Methods

Results

Discussion

Conclusion