Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton's jelly and bone marrow-derived mesenchymal stem cells.
Differential expression of cell cycle and WNT pathway-related genes accounts for differences in the growth and differentiation potential of Wharton's jelly and bone marrow-derived mesenchymal stem cells.
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DOI：
10.1186/s13287-017-0555-9
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发表时间：
2017-04-26
影响因子：
7.5
通讯作者：
Papadaki HA
中科院分区：
文献类型：
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作者：
Batsali AK;Pontikoglou C;Koutroulakis D;Pavlaki KI;Damianaki A;Mavroudi I;Alpantaki K;Kouvidi E;Kontakis G;Papadaki HA
鉴于目前对探索不同来源的间充质干细胞（MSC）的临床应用的兴趣，我们对从脐带中最丰富的MSC来源沃顿氏胶（WJ）中分离的MSC与骨髓（BM）-MSC（研究最广泛的MSC群体）的生物学特性进行了并排比较。从血液健康供体的BM抽吸物（n = 18）和足月新生儿的WJ（n = 18）分离并扩增MSC。我们在平行实验中评估了MSC的免疫表型、存活和衰老特征以及它们的增殖潜力和细胞周期分布。我们还评估了与WNT和细胞周期信号通路相关的基因的表达，并通过传代进行核型分析以评估MSC基因组的稳定性。通过评估MSC与BM或脐带血来源的CD 34+细胞共培养物的非粘附部分中的克隆形成细胞以及通过测量MSC培养上清液中的造血细胞因子水平来研究来自两种来源的MSC的造血支持能力。最后，我们评估了MSC分化为脂肪细胞和骨细胞的能力，以及WNT相关分子WISP-1和sFRP 4对WJ-MSC分化潜力的影响。两种体外扩增的MSC群体显示出相似的形态学、免疫表型、存活和衰老特征，并且在传代过程中以低频率获得基因组改变。WJ-MSCs表现出更高的增殖潜力，这可能是由于刺激细胞增殖的基因的上调沿着与细胞周期抑制相关的基因的下调。与BM-MSCs相比，WJ-MSCs表现出较差的向骨细胞和脂肪细胞的谱系启动和分化能力。这一发现与WNT信号相关分子的差异表达有关，包括WISP 1和sFRP 4，具体研究了它们在WJ-MSC分化潜力中的各自作用。有趣的是，用重组人WISP 1或sFRP 4处理WJ-MSC分别诱导成骨和脂肪形成。与BM-MSCs相比，WJ-MSCs表现出较差的造血支持潜力，可能是由于基质细胞衍生因子-1 α的产生减少。总的来说，这些数据预计将有助于更好地表征WJ-MSC和BM-MSC的潜在临床应用。
In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton’s jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population. MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs. Both ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs. Overall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications.