Tiss Engin Part A：科学家开发出骨骼再生新技术

日本研究人员1日在美国《组织工程学》Tissue Engineering Part A杂志上报告说，他们在动物实验中仅利用干细胞的培养液就实现了动物受损骨骼的再生。而以往实现骨骼再生，需要利用来自骨髓的干细胞。

日本名古屋大学教授上田实率领的研究小组发现，在干细胞的培养液中，有一些细胞因子可以调整细胞的增殖和死亡。

研究人员于是将这种培养液先涂到生物医学材料胶原蛋白海绵上，再将其移植到缺失了部分头盖骨的实验鼠头上。4周后，这些实验鼠头盖骨缺失的部分有90％以上实现了再生。

研究人员还发现，实验鼠体内的干细胞会大量集中到头盖骨移植了胶原蛋白海绵的部分。这说明，干细胞培养液具有汇集干细胞的效果。

研究人员下一步将展开人类临床试验。上田实指出，此前移植干细胞的传统方法存在细胞发生癌变的风险，而新方法可以大大降低这种风险。

doi:10.1089/ten.tea.2011.0325
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Conditioned Media from Mesenchymal Stem Cells Enhanced Bone Regeneration in Rat Calvarial Bone Defects

Masashi Osugi, D.D.S., Wataru Katagiri, D.D.S., Ph.D., Ryoko Yoshimi, D.D.S., Ph.D., Takeharu Inukai, D.D.S., Hideharu Hibi, D.D.S., Ph.D., and Minoru Ueda, D.D.S., Ph.D.

Tissue engineering has recently become available as a treatment procedure for bone augmentation. However, this procedure has several problems, such as high capital investment and expensive cell culture, complicated safety and quality management issues regarding cell handling, and patient problems with the invasive procedure of cell collection. Moreover, it was reported that stem cells secrete many growth factors and chemokines during their cultivation, which could affect cellular characteristics and behavior. This study investigated the effect of stem-cell-cultured conditioned media on bone regeneration. Cultured conditioned media from human bone marrow–derived mesenchymal stem cells (MSC-CM) enhanced the migration, proliferation, and expression of osteogenic marker genes, such as osteocalcin and Runx2, of rat MSCs (rMSCs) in vitro. MSC-CM includes cytokines such as insulin-like growth factor-1 and vascular endothelial growth factor. In vivo, a prepared bone defect of a rat calvarial model was implanted in five different rat groups using one of the following graft materials: human MSCs/agarose (MSCs), MSC-CM/agarose (MSC-CM), Dulbecco's modified Eagle's medium without serum [DMEM(−)]/agarose [DMEM(−)], PBS/agarose (PBS), and defect only (Defect). After 4 and 8 weeks, implant sections were evaluated using microcomputed tomography (micro-CT) and histological analysis. Micro-CT analysis indicated that the MSC-CM group had a greater area of newly regenerated bone compared with the other groups (p<0.05) and histological analysis at 8 weeks indicated that the newly regenerated bone bridge almost covered the defect. Interestingly, the effects of MSC-CM were stronger than those of the MSC group. In vivo imaging and immunohistochemical staining of transgenic rats expressing green fluorescent protein also showed that migration of rMSCs to the bone defect in the MSC-CM group was greater than in the other groups. These results demonstrated that MSC-CM can regenerate bone through mobilization of endogenous stem cells. The use of stem-cell-cultured conditioned media for bone regeneration is a unique concept that utilizes paracrine factors of stem cells without cell transplantation.