Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy
Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy
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DOI：
10.3390/ijms140917986
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发表时间：
2013-09-01
影响因子：
5.6
通讯作者：
Chang, Jong Wook
中科院分区：
文献类型：
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作者：
Jin, Hye Jin;Bae, Yun Kyung;Chang, Jong Wook
各种来源的间充质干细胞（MSC）已被认为是不治之症的细胞治疗。为了表征来自不同来源的MSC，我们比较了人骨髓（BM）、脂肪组织（AT）和脐带血来源的MSC（UCB-MSC）的表面抗原表达、分化能力、增殖能力、克隆性、对衰老的耐受性和旁分泌活性。虽然来自不同组织的MSC具有相似的表面抗原表达水平、免疫抑制活性和分化能力，但UCB-MSC具有最高的细胞增殖率和克隆性，并且显著降低了p53、p21和p16的表达，这些是众所周知的衰老标志物。由于旁分泌作用是间充质干细胞的主要作用，我们研究了脂多糖（LPS）诱导的炎症下的每个MSC的抗炎活性。UCB-MSCs与LPS处理的大鼠肺泡巨噬细胞共培养，通过血管生成素-1（Ang-1）降低炎性细胞因子包括白细胞介素-1（IL-1）、IL-6和IL-8的表达。使用重组Ang-1作为潜在的可溶性旁分泌因子或其小干扰RNA（siRNA），我们发现Ang-1分泌部分通过预防炎症来负责这种有益作用。我们的研究结果表明，原始的UCB-MSCs相比，成人来源的生物学优势，使UCB-MSCs的细胞治疗的临床应用的一个有用的模型。
Various source-derived mesenchymal stem cells (MSCs) have been considered for cell therapeutics in incurable diseases. To characterize MSCs from different sources, we compared human bone marrow (BM), adipose tissue (AT), and umbilical cord blood-derived MSCs (UCB-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, and paracrine activity. Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence. Since paracrine action is the main action of MSCs, we examined the anti-inflammatory activity of each MSC under lipopolysaccharide (LPS)-induced inflammation. Co-culture of UCB-MSCs with LPS-treated rat alveolar macrophage, reduced expression of inflammatory cytokines including interleukin-1 (IL-1), IL-6, and IL-8 via angiopoietin-1 (Ang-1). Using recombinant Ang-1 as potential soluble paracrine factor or its small interference RNA (siRNA), we found that Ang-1 secretion was responsible for this beneficial effect in part by preventing inflammation. Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy.