Siddappa Ramakrishnaiah, Fernandes Hugo, Liu Jun, van Blitterswijk Clemens, de Boer Jan
University of Twente, Institute for BioMedical Technology, Department of Tissue Regeneration, P.O. Box 217, Enschede 7500 AE, The Netherlands.
Curr Stem Cell Res Ther. 2007 Sep;2(3):209-20. doi: 10.2174/157488807781696267.
Bone tissue engineering using human mesenchymal stem cells (hMSCs) is a multidisciplinary field that aims to treat patients with trauma, spinal fusion and large bone defects. Cell-based bone tissue engineering encompasses the isolation of multipotent hMSCs from the bone marrow of the patient, in vitro expansion and seeding onto porous scaffold materials. In vitro pre-differentiation of hMSCs into the osteogenic lineage augments their in vivo bone forming capacity. Differentiation of hMSCs into bone forming osteoblasts is a multi-step process regulated by various molecular signaling pathways, which warrants a thorough understanding of these signaling cues for the efficient use of hMSCs in bone tissue engineering. Recently, there has been a surge of knowledge on the molecular cues regulating osteogenic differentiation but extrapolation to hMSC differentiation is not guaranteed, because of species- and cell-type specificity. In this review, we describe a number of key osteogenic signaling pathways, which directly or indirectly regulate osteogenic differentiation of hMSCs. We will discuss how and to what extent the process is different from that in other cell types with special emphasis on applications in bone tissue engineering.
利用人间充质干细胞(hMSCs)进行骨组织工程是一个多学科领域,旨在治疗创伤、脊柱融合和大骨缺损患者。基于细胞的骨组织工程包括从患者骨髓中分离多能hMSCs、体外扩增并接种到多孔支架材料上。hMSCs在体外预分化为成骨谱系可增强其体内成骨能力。hMSCs分化为成骨的成骨细胞是一个由多种分子信号通路调控的多步骤过程,这就需要深入了解这些信号线索,以便在骨组织工程中有效利用hMSCs。最近,关于调控成骨分化的分子线索的知识激增,但由于物种和细胞类型的特异性,不能保证将其外推到hMSC分化。在本综述中,我们描述了一些关键的成骨信号通路,它们直接或间接调节hMSCs的成骨分化。我们将讨论该过程与其他细胞类型的过程在何种程度上不同,并特别强调其在骨组织工程中的应用。