Griffin Michelle, Ryan Caroline M, Pathan Omar, Abraham David, Denton Christopher P, Butler Peter E M
Charles Wolfson Center for Reconstructive Surgery, Royal Free Hospital, London, UK.
Division of Surgery & Interventional Science, University College London, London, UK.
Stem Cell Res Ther. 2017 Feb 7;8(1):23. doi: 10.1186/s13287-016-0444-7.
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.
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.
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.
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.
脂肪来源干细胞(ADSCs)正逐渐成为基于细胞疗法的另一种干细胞来源。近期数据表明,富含自体ADSC的微移植可改善系统性硬化症(SSc)面部受累情况。我们已对SSc患者的ADSCs进行了广泛表征,并将其表型和功能与年龄和性别匹配的健康对照ADSCs进行了比较。
从6例SSc患者队列(ADSC-SSc)中分离并表征ADSCs,并与6例年龄和性别匹配的健康对照(ADSC-N)进行比较。通过对间充质和造血标志物的流式细胞术分析以及向软骨生成、成骨和成脂谱系分化的能力,探索细胞表面表型谱系定向。通过生化和细胞试验评估ADSCs的增殖、代谢、黏附、形态、迁移和侵袭等功能活性。
对ADSC-SSc进行表征时,我们发现与健康匹配的对照ADSCs相比,其表型或表面抗原表达没有改变。我们发现ADSC-SSc的分化能力与ADSC-N相当,且ADSC-SSc未表现出任何形态或黏附异常。我们发现ADSC-SSc的增殖率和代谢活性降低(p<0.01)。我们发现与健康匹配的对照ADSCs相比,ADSC-SSc的迁移和侵袭能力降低(p<0.01)。
本研究提供了重要发现,可对SSc患者的ADSCs进行差异性表征。结果表明,SSc患者ADSCs的表面表型和分化能力与健康匹配的ADSCs相同。虽然研究结果表明ADSC-SSc的增殖和迁移能力降低,但ADSC-SSc能够进行体外培养和扩增。这些发现鼓励进一步研究ADSCs影响组织纤维化的机制。