In vivo bone-forming capacity of human bone marrow-derived stromal cells is stimulated by recombinant human bone morphogenetic protein-2
In vivo bone-forming capacity of human bone marrow-derived stromal cells is stimulated by recombinant human bone morphogenetic protein-2
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重组人骨形态发生蛋白2刺激人骨髓基质细胞的体内成骨能力
DOI：
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发表时间：
2001
影响因子：
3.3
通讯作者：
Hideaki Takahashi
中科院分区：
文献类型：
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作者：
H. Yamagiwa;N. Endo;K. Tokunaga;T. Hayami;H. Hatano;Hideaki Takahashi
摘要在本研究中，我们研究了重组人骨形态发生蛋白-2 （rhBMP-2）是否能增强人骨髓源性基质细胞（HMSCs）的体内成骨能力。从7个供体（5-54岁）获得的HMSCs传代3 - 6次。传代的HMSCs在体外表现出成骨细胞表型，包括：(a)碱性磷酸酶（ALP）活性对地塞米松、抗坏血酸和β-甘油磷酸酯的反应增加；(b)逆转录-聚合酶链反应检测成骨细胞谱系标志物（ALP、骨桥蛋白、骨钙素和甲状旁腺激素受体）和BMP-2、-4和-6的mRNA表达。在体内实验中，将移植物皮下植入裸鼠：A组（载体）；B组（rhBMP-2）；C组（带载体的HMSCs）；D组（含rhBMP-2的HMSCs）。移植后2周和4周分别进行移植。相关影像学检查、组织学观察和物种特异性探针原位杂交显示，B组移植含有小鼠来源的骨组织，在移植的周围观察到。植入4周后，c组7个移植物中有2个在周围检测到少量hmscs来源的骨组织，而D组7个移植物中有5个显示出hmscs来源的骨组织，位于移植物的中心，被小鼠骨组织包围。此外，7例D组移植中有2例检测到hmsc来源的软骨形成。本研究结果表明，培养扩增的HMSCs保留了成骨细胞表型，并且rhBMP-2可以促进体内成骨能力。
Abstract In the present study, we investigated whether the in vivo bone-forming capacity of human bone marrow-derived stromal cells (HMSCs) could be enhanced by recombinant human bone morphogenetic protein-2 (rhBMP-2). The HMSCs obtained from seven donors (5–54 years of age) were passaged three to six times. Passaged HMSCs exhibited the osteoblastic phenotype in vitro, including: (a) an increase in alkaline phosphatase (ALP) activity in response to dexamethasone, ascorbic acid, and β-glycerophosphate; and (b) mRNA expression for markers of osteoblastic lineage (ALP, osteopontin, osteocalcin, and parathyroid hormone-receptor) and BMP-2, -4, and -6 detected by reverse transcription–polymerase chain reaction. For the in vivo assay, transplants were subcutaneously implanted into nude mice as follows: group A (vehicle); group B (rhBMP-2); group C (HMSCs with vehicle); and group D (HMSCs with rhBMP-2). Transplants were obtained 2 and 4 weeks after implantation. Correlated radiographic findings, histological observations, and in situ hybridization using species-specific probes showed that the group B transplants contained bone tissue of mouse origin, which was observed at the periphery of the transplants. Four weeks after implantation, small amounts of HMSCs-derived bone tissue were detected at the periphery in two of seven transplants in group C. In contrast, five of seven group D transplants exhibited HMSCs-derived bone tissue, which was located at the center of the transplants and was surrounded by mouse bone tissue. Furthermore, HMSCs-derived chondrogenesis was detected in two of seven group D transplants. The results of the present study demonstrate that culture-expanded HMSCs preserve the osteoblastic phenotype, and the in vivo bone-forming capacity can be promoted by rhBMP-2.
DOI：
10.1073/pnas.92.11.4857
发表时间：
1995-05-23
影响因子：
11.1
作者：
PEREIRA, RF;HALFORD, KW;PROCKOP, DJ
通讯作者：
PROCKOP, DJ
影响因子：
4.8
作者：
Su‐Li Cheng;J. Yang;L. Rifas;Shu-Fang Zhang;L. Avioli
通讯作者：
Su‐Li Cheng;J. Yang;L. Rifas;Shu-Fang Zhang;L. Avioli