Schneider R K, Neuss S, Knüchel R, Perez-Bouza A
Institut für Pathologie, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen.
Pathologe. 2010 Oct;31 Suppl 2:138-46. doi: 10.1007/s00292-010-1329-7.
Human mesenchymal stem cells (MSC) represent an attractive option for cell replacement strategies (tissue engineering, TE). TE applications require stability of a stem cell/biomaterial-hybrid via cell migration, matrix-remodelling and differentiation. We focus on these mechanisms in organotypic culture systems for bone TE using MSC from the umbilical cord (UC-MSC) and from bone marrow (BM-MSC). For the organotypic differentiation of MSC into functional osteoblasts, MSC were embedded in a collagenous matrix and subjected to osteogenic differentiation. Under these culture conditions, UC-MSC exceeded BM-MSC in the expression and synthesis of extracellular matrix (ECM) proteins, while BM-MSC show enhanced osteogenic gene upregulation. In both cell types the biosynthetic activity was accompanied by the ultrastructural appearance of hydroxyapatite/calcium crystals. Following secretion of matrix metalloproteinases, both MSC types migrated into and colonised the collagenous matrix causing matrix strengthening and contraction. In conclusion, MSC promise a broad therapeutical application for a variety of connective tissues requiring ECM synthesis and remodelling.
人间充质干细胞(MSC)是细胞替代策略(组织工程,TE)的一个有吸引力的选择。TE应用需要通过细胞迁移、基质重塑和分化来实现干细胞/生物材料杂交体的稳定性。我们使用来自脐带(UC-MSC)和骨髓(BM-MSC)的MSC,在用于骨TE的器官型培养系统中关注这些机制。为了将MSC定向分化为功能性成骨细胞,将MSC嵌入胶原基质中并进行成骨分化。在这些培养条件下,UC-MSC在细胞外基质(ECM)蛋白的表达和合成方面超过BM-MSC,而BM-MSC则显示出增强的成骨基因上调。在这两种细胞类型中,生物合成活性都伴随着羟基磷灰石/钙晶体的超微结构出现。在分泌基质金属蛋白酶后,两种类型的MSC都迁移到胶原基质中并在其中定植,导致基质强化和收缩。总之,MSC有望广泛应用于各种需要ECM合成和重塑的结缔组织的治疗。