Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation
Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation
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DOI：
10.1038/sj.cdd.4402121
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发表时间：
2007-06-01
影响因子：
12.4
通讯作者：
Papaccio, G.
中科院分区：
文献类型：
--
作者：
d'Aquino, R.;Graziano, A.;Papaccio, G.
将人牙髓基质干细胞(SBP-DPSCS)用于体外和体内成骨分化的研究。我们以前报道过SBP-DPSCs是一种多能干细胞，能够分化为成骨细胞，在体外合成三维编织骨组织芯片。在本研究中，我们跟踪了SBP-DPSCs中特异性标志物的时间表达模式，发现在分化为成骨细胞时，它们除了表达骨钙素外，还表达Flk-1(血管内皮生长因子-R2)。此外，30%的细胞表达内皮细胞特异性抗原，包括CD54、von-Willebrand(结构域1和2)、CD31(PECAM-1)和血管紧张素转换酶。有趣的是，我们发现内皮细胞形成血管壁，观察到干细胞协同分化为成骨细胞和内皮细胞，并且Flk-1在成骨细胞和内皮细胞分化的耦合中发挥关键作用。无论是SBP-DPSCs还是体外获得的骨芯片移植到免疫低下的大鼠体内，它们都会产生一种与成人骨相似的完整血供的组织结构；事实上，在骨内或骨膜层中观察到大量的人类白细胞抗原-1(+)血管。本研究提供了直接证据表明，人SBP-DPSCs介导的成骨和血管生成可能受不同机制的调控，导致干细胞移植后成人骨组织的组织。
Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP-DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize three-dimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand ( domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1(+) vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantion.