Osteoblasts derived from induced pluripotent stem cells form calcified structures in scaffolds both in vitro and in vivo.
Osteoblasts derived from induced pluripotent stem cells form calcified structures in scaffolds both in vitro and in vivo.
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DOI：
10.1002/stem.566
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发表时间：
2011-02
期刊：
影响因子：
5.2
通讯作者：
Majka, Susan M.
中科院分区：
文献类型：
--
作者：
Bilousova, Ganna;Jun, Du Hyun;King, Karen B.;De Langhe, Stijn;Chick, Wallace S.;Torchia, Enrique C.;Chow, Kelsey S.;Klemm, Dwight J.;Roop, Dennis R.;Majka, Susan M.
将体细胞重新编程为胚胎干细胞(ES)样状态，或诱导多能干细胞(IPS)，已成为定制细胞治疗的一个有前途的新场所。在这项研究中，我们通过定向分化来评估小鼠iPS细胞在体外分化为骨、软骨和脂肪的能力，并在体外和体内保持支架上的成骨细胞表型。取小鼠iPS细胞来源的类胚体，在分化培养液中培养8~12周。通过谱系特异性形态、基因表达、组织学染色和免疫染色检测基质沉积来评价分化程度。扩增12周后，将iPS来源的成骨细胞种植于明胶海绵基质中，然后皮下植入同基因ICR小鼠。12周后取材，进行细胞、矿物质和基质含量的组织学分析。形态和谱系特异性基因的表达证实了iPS细胞分化为骨、软骨和脂肪的间充质谱系。IPS细胞来源的成骨细胞的单独移植表达骨特有的基质，包括骨钙素和骨涎蛋白。种植体也被茜素红和von Kossa染色，显示矿化和成骨细胞表型的持久性。还检测到了种植体的血管再生和微血管形成。综上所述，这些数据显示了iPS细胞在体外和体内的功能性成骨细胞分化，并揭示了一种值得评估其在骨科医学中的潜在用途和了解骨科疾病分子机制的细胞来源。
Reprogramming somatic cells into an embryonic stem (ES) cell-like state, or induced pluripotent stem (iPS) cells, has emerged as a promising new venue for customized cell therapies. In this study, we performed directed differentiation to assess the ability of murine iPS cells to differentiate into bone, cartilage and fat in vitro and to maintain an osteoblast phenotype on a scaffold in vitro and in vivo. Embryoid bodies derived from murine iPS cells were cultured in differentiation medium for eight to twelve weeks. Differentiation was assessed by lineage specific morphology, gene expression, histological stain and immunostaining to detect matrix deposition. After 12 weeks of expansion, iPS derived osteoblasts were seeded in a gelfoam matrix followed by subcutaneous implantation in syngenic ICR mice. Implants were harvested at 12 weeks, and histological analyses of cell, mineral and matrix content were performed. Differentiation of iPS cells into mesenchymal lineages of bone, cartilage and fat was confirmed by morphology, and expression of lineage specific genes. Isolated implants of iPS cell derived osteoblasts expressed matrices characteristic of bone, including osteocalcin and bone sialoprotein. Implants were also stained with alizarin red and von Kossa, demonstrating mineralization and persistence of an osteoblast phenotype. Recruitment of vasculature and microvascularization of the implant was also detected. Taken together, these data demonstrate functional osteoblast differentiation from iPS cells both in vitro and in vivo and reveal a source of cells which merit evaluation for their potential uses in orthopaedic medicine and understanding of molecular mechanisms of orthopaedic disease.
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影响因子：
15.8
作者：
Barberi T;Willis LM;Socci ND;Studer L
通讯作者：
Studer L
影响因子：
158.5
作者：
Kainer, MA;Linden, JV;Archibald, LK
通讯作者：
Archibald, LK
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4.1
作者：
Kawaguchi, J;Mee, PJ;Smith, AG
通讯作者：
Smith, AG
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46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.
影响因子：
23.9
作者：
Marion, Rosa M.;Strati, Katerina;Blasco, Maria A.
通讯作者：
Blasco, Maria A.