Batsali Aristea K, Pontikoglou Charalampos, Koutroulakis Dimitrios, Pavlaki Konstantia I, Damianaki Athina, Mavroudi Irene, Alpantaki Kalliopi, Kouvidi Elisavet, Kontakis George, Papadaki Helen A
University of Crete School of Medicine, Heraklion, Greece.
Graduate Program "Molecular Basis of Human Disease", University of Crete School of Medicine, Heraklion, Greece.
Stem Cell Res Ther. 2017 Apr 26;8(1):102. doi: 10.1186/s13287-017-0555-9.
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.
鉴于目前对探索不同来源间充质干细胞（MSCs）临床应用的兴趣，我们对从脐带中最丰富的MSCs来源——华通氏胶（WJ）分离的MSCs与研究最广泛的MSCs群体——骨髓（BM）-MSCs的生物学特性进行了并行比较。
从血液学健康供体的骨髓抽吸物（n = 18）和足月新生儿的WJ（n = 18）中分离并扩增MSCs。在平行实验中，我们评估了MSCs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表达，并通过传代进行核型分析以评估MSCs的基因组稳定性。通过评估与BM或脐带血来源的CD34细胞共培养的MSCs非贴壁部分中的克隆形成细胞以及测量MSCs培养上清液中的造血细胞因子水平，研究了两种来源的MSCs的造血支持能力。最后，我们评估了MSCs分化为脂肪细胞和骨细胞的能力以及WNT相关分子WISP-1和sFRP4对WJ-MSCs分化潜能的影响。
两种体外扩增的MSCs群体均表现出相似的形态、免疫表型、存活和衰老特征，并且在传代过程中低频获得基因组改变。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上调以及与细胞周期抑制相关的基因下调。与BM-MSCs相比，WJ-MSCs向骨细胞和脂肪细胞的谱系启动和分化能力较差。这一发现与WNT信号相关分子的差异表达有关，包括WISP1和sFRP4，我们专门研究了它们在WJ-MSCs分化潜能中的各自作用。有趣的是，用重组人WISP1或sFRP4处理WJ-MSCs分别导致成骨和成脂诱导。与BM-MSCs相比，WJ-MSCs的造血支持潜力较差，可能是由于基质细胞衍生因子-1α的产生减少。
总体而言，这些数据有望有助于更好地表征WJ-MSCs和BM-MSCs以用于潜在的临床应用。
