Departamento de Genética e Evolução, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Departamento de Genética e Evolução, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Bone. 2018 Jan;106:112-120. doi: 10.1016/j.bone.2017.10.014. Epub 2017 Oct 13.
A more accurate understanding of the molecular mechanisms and signaling pathways underpinning human mesenchymal stem cell (MSC) plasticity and differentiation properties is pivotal for accomplishing solid and diligent translation of MSC-based experimental therapeutics and clinical trials to broad clinical practice. In addition, this knowledge enables selection of MSC subpopulations with increased differentiation potential and/or use of exogenous factors to boost this potential. Here, we report that CD105 (ENG) is a predictive biomarker of osteogenic potential in two types of MSCs: stem cells from human exfoliated deciduous teeth (SHED) and human adipose-derived stem cells (hASC). We also validate that CD105 can be used to select and enrich for subpopulations of SHED and hASC with higher in vitro osteogenic potential. In addition, we show that hsa-mir-1287 regulates CD105 expression, and propose that fine-tuning hsa-mir-1287 levels could be used to control osteopotential in SHED. These findings provide better discernment of the molecular bases behind MSC osteogenic plasticity and open up new perspectives to leverage osteogenic potential in MSCs by modulation of a specific miRNA.
更准确地了解支撑人类间充质干细胞（MSC）可塑性和分化特性的分子机制和信号通路，对于将基于 MSC 的实验治疗和临床试验扎实而勤奋地转化为广泛的临床实践至关重要。此外，这一知识还可以帮助选择具有更高分化潜力的 MSC 亚群，或利用外源性因素来增强这种潜力。在这里，我们报告 CD105（ENG）是两种类型的 MSC（人脱落乳牙来源的干细胞（SHED）和人脂肪来源的干细胞（hASC））成骨潜能的预测性生物标志物。我们还验证了 CD105 可用于选择和富集具有更高体外成骨潜能的 SHED 和 hASC 亚群。此外，我们还表明 hsa-mir-1287 调节 CD105 的表达，并提出精细调节 hsa-mir-1287 的水平可用于控制 SHED 中的成骨潜能。这些发现为 MSC 成骨可塑性背后的分子基础提供了更好的认识，并为通过调节特定的 miRNA 来利用 MSC 的成骨潜力开辟了新的视角。
