Differentiating multipotent mesenchymal stromal cells generate factors that exert paracrine activities on exogenous MSCs: Implications for paracrine activities in bone regeneration
Differentiating multipotent mesenchymal stromal cells generate factors that exert paracrine activities on exogenous MSCs: Implications for paracrine activities in bone regeneration
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DOI：
10.1016/j.bbrc.2012.08.095
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发表时间：
2012-10-05
影响因子：
3.1
通讯作者：
Niyibizi, Christopher
中科院分区：
文献类型：
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作者：
Li, Feng;Whyte, Noelle;Niyibizi, Christopher
多能间充质基质细胞（MSCs）移植到宿主组织后促进组织修复的机制仍然知之甚少。目前的概念表明，除了分化成宿主组织的细胞外，MSC还产生调节宿主组织微环境以帮助修复过程的营养因子。在这篇文章中，我们评估了MSC在成骨分化过程中分泌的因子是否诱导外源性MSC中成骨细胞标志物的表达以及它们的迁移。将小鼠骨髓间充质干细胞在成骨培养基中培养，在不同时间点收集细胞条件培养液，观察其对外源性骨髓间充质干细胞分化和迁移的影响。此外，我们确定了骨髓间充质干细胞注入小鼠股骨是否表达基因编码的因素预测发挥作用的旁分泌活动。结果表明，MSCs在成骨培养液中维持生长，并在特定时间点分泌诱导外源性MSCs碱性磷酸酶活性的因子，并诱导其迁移。MSC注入小鼠股骨，并在不同的日子检索表达的基因编码的预测因子，在细胞分化和迁移中发挥作用。骨形态发生蛋白-2（BMP-2）的中和抗体导致外源性MSC的ALP活性降低。这些数据表明，随着MSC向成骨谱系分化，它们分泌诱导内源性祖细胞募集和分化的因子。这些数据揭示了供体间充质干细胞可能有助于骨修复过程的机制，并为设计肌肉骨骼疾病的干细胞治疗方法提供了平台。(C)2012 Elsevier Inc. All rights reserved.
The mechanisms by which multipotent mesenchymal stromal cells (MSCs) contribute to tissue repair following transplantation into host tissues remains poorly understood. Current concepts suggest that, in addition to differentiation into cells of the host tissues, MSCs also generate trophic factors that modulate host tissue microenvironment to aid in the repair process. In this communication, we assessed whether factors secreted by MSCs undergoing osteogenic differentiation induce expression of osteoblast markers in exogenous MSCs as well as their migration. Murine MSCs were cultured in osteogenic medium, and at different time points, medium conditioned by the cells was collected and assessed for its effects on differentiation and migration of exogenous MSCs. In addition, we determined whether MSCs infused into mice femurs expressed genes encoding for factors predicted to play a role in paracrine activities. The results showed that MSCs maintained in osteogenic medium, secreted factors at specific time points that induced alkaline phosphatase activity (ALP) in exogenous MSCs as well as their migration. MSCs infused into mice femurs and retrieved at different days expressed genes that encoded predicted factors that play a role in cell differentiation and migration. Neutralizing antibodies to bone morphogenetic protein-2 (BMP-2) led to the decrease in ALP activity by exogenous MSCs. These data demonstrated that, as MSCs differentiate toward osteogenic lineage, they secrete factors that induce recruitment and differentiation of endogenous progenitors. These data reveal mechanisms by which donor MSCs may contribute to the bone reparative process and provide a platform for designing approaches for stem cell therapies of musculoskeletal disorders. (C) 2012 Elsevier Inc. All rights reserved.