Characteristics of human adipose derived stem cells in scleroderma in comparison to sex and age matched normal controls: implications for regenerative medicine

与性别和年龄匹配的正常对照者相比,硬皮病患者脂肪干细胞的特征:对再生医学的意义

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作者:Michelle Griffin, Caroline M Ryan, Omar Pathan, David Abraham, Christopher P Denton, Peter E M Butler

Background

Adipose-derived stem cells (ADSCs) are emerging as an alternative stem cell source for cell-based therapies. Recent data suggest that autologous ADSC-enriched micrografting improves the effects of facial involvement in systemic sclerosis (SSc). We have extensively characterised ADSCs from SSc patients and compared their phenotype and function to healthy age- and sex-matched control ADSCs.

Conclusions

This study provides important findings that can differentially characterise ADSCs from SSc patients. Results indicate that the surface phenotype and differentiation capacity of ADSCs from SSc patients are identical to healthy matched ADSCs. While the findings indicate that the proliferation and migration capacity of ADSC-SSc is reduced, ADSC-SSc are capable of ex-vivo culture and expansion. These findings encourage further investigation into the understanding by which ADSCs can impact upon tissue fibrosis.

Methods

ADSCs were isolated and characterised from a cohort of six SSc patients (ADSC-SSc) and were compared to six healthy age- and sex-matched controls (ADSC-N). Cell surface phenotype lineage commitment was explored by flow cytometric analysis of mesenchymal and hematopoietic markers and by the capacity to differentiate to chondrogenic, osteogenic, and adipogenic lineages. Functional activities of ADSCs were assessed by biochemical and cellular assays for proliferation, metabolism, adhesion, morphology, migration, and invasion.

Results

Upon characterization of ADSC-SSc, we found that there was no alteration in the phenotype or surface antigen expression compared to healthy matched control ADSCs. We found that the differentiation capacity of ADSC-SSc was equivalent to that of ADSC-N, and that ADSC-SSc did not display any morphological or adhesive abnormalities. We found that the proliferation rate and metabolic activity of ADSC-SSc was reduced (p < 0.01). We found that the migration and invasion capacity of ADSC-SSc was reduced (p < 0.01) compared to healthy matched control ADSCs. Conclusions: This study provides important findings that can differentially characterise ADSCs from SSc patients. Results indicate that the surface phenotype and differentiation capacity of ADSCs from SSc patients are identical to healthy matched ADSCs. While the findings indicate that the proliferation and migration capacity of ADSC-SSc is reduced, ADSC-SSc are capable of ex-vivo culture and expansion. These findings encourage further investigation into the understanding by which ADSCs can impact upon tissue fibrosis.

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