The New York Stem Cell Foundation, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8680-5. doi: 10.1073/pnas.1301190110. Epub 2013 May 7.
Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.
先天性缺陷、创伤和疾病会损害骨骼系统的完整性和功能，在需要植入骨移植物的情况下尤其如此。能够个性化定制以满足特定临床需求的、具有活力的骨替代物的工程设计代表了一种很有前途的治疗选择。我们的研究目的是评估人诱导多能干细胞（hiPSC）在骨组织工程中的应用。我们首先将三种具有不同组织和重编程背景的 hiPSC 系诱导为间充质系，并使用一系列分化测定、表面抗原分析和全基因表达分析来鉴定具有强成骨分化潜力的系。然后，我们通过在灌注生物反应器中的骨诱导性支架上培养 hiPSC 衍生的间充质祖细胞来构建功能性骨替代物，并在皮下植入模型中确认其表型稳定性长达 12 周。分子分析证实，在灌注生物反应器中培养骨替代物可导致细胞增殖的全局抑制和谱系特异性基因的表达增加。这些结果为生长患者特异性骨替代物以进行骨骼系统的重建治疗以及构建发育和疾病的合格实验模型铺平了道路。
