Characterization of human adipose tissue-derived stromal cells isolated from diabetic patient's distal limbs with critical ischemia
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25251698
DOI
10.1002/cbf.3056
Knihovny.cz E-resources
- Keywords
- adipose tissue, cell therapy, diabetes, differentiation, flow cytometry, mesenchymal stem cells,
- MeSH
- Biomarkers metabolism MeSH
- Cell Differentiation MeSH
- Stromal Cells cytology metabolism MeSH
- Antigens, CD metabolism MeSH
- Chondrocytes cytology metabolism MeSH
- Cytokines metabolism MeSH
- Diabetes Mellitus pathology MeSH
- Diabetic Foot pathology MeSH
- Adult MeSH
- Endoglin MeSH
- Fibroblasts cytology metabolism MeSH
- Ischemia pathology MeSH
- Extremities blood supply pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mesenchymal Stem Cells cytology metabolism MeSH
- Osteoblasts cytology metabolism MeSH
- Subcutaneous Fat cytology MeSH
- Receptors, Cell Surface metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Adipocytes cytology metabolism MeSH
- Vascular Endothelial Growth Factor A metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
- Antigens, CD MeSH
- Cytokines MeSH
- Endoglin MeSH
- ENG protein, human MeSH Browser
- Receptors, Cell Surface MeSH
- Vascular Endothelial Growth Factor A MeSH
Adipose tissue is an abundant source of autologous adult stem cells that may bring new therapeutic perspectives on the treatment of diabetes and its complications. It is unclear whether adipose tissue-derived stromal cells (ASCs) of diabetic patients, constantly influenced by hyperglycaemia, have the same properties as non-diabetic controls. As an alternative source of ASCs, adipose tissue from distal limbs of diabetic patients with critical ischemia was isolated. ASCs were characterized in terms of cell surface markers, multilineage differentiation and the expression of vascular endothelial growth factor (VEGFA), chemokine-related genes and compared with non-diabetic controls. Flow cytometry analysis confirmed mesenchymal phenotypes in both diabetic and non-diabetic ASCs. Nevertheless, 40% of diabetic and 20% of non-diabetic ASC samples displayed high expressions of fibroblast marker, which inversely correlated with the expression of CD105. In diabetic patients, significantly decreased expression of VEGFA and chemokine receptor CXCR4 was found in fibroblast-positive ASCs, compared with their fibroblast-negative counterparts. Reduced osteogenic differentiation and the downregulation of chemokine CXCL12 were found in fibroblast-negative diabetic ASCs. Both diabetic and non-diabetic ASCs were differentiated into adipocytes and chondrocytes and did not reveal islet-like cell differentiation. According to this study, adipose tissue from distal limbs of diabetic patients is not satisfactory as an autologous ASC source. Hyperglycaemic milieu as well as other metabolic disorders linked to diabetes may have an influence on endogenous stem cell properties. The present study investigated the feasibility of autologous stem cell therapy in diabetic patients. ASCs isolated from the ischemic limb of diabetic patients were found to be less potent when compared phenotypically and functionally to control non-diabetic counterparts with no signs of limb ischemia. High expression of fibroblast markers associated with reduced expression of VEGFA as well as reduced osteogenic differentiation may have an impact on the effectiveness of autologous cell therapies in diabetic patients.
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