Dental pulp stem cells and regeneration
Dental pulp stem cells and regeneration
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DOI：
10.1111/etp.12027
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
M. Nakashima;K. Iohara;M. Murakami
中科院分区：
文献类型：
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作者：
M. Nakashima;K. Iohara;M. Murakami
牙髓源性干细胞（DPSC）被认为是用于组织修复和再生医学的巨大希望。DPSC可以很容易地从废弃的牙齿中收集，几乎没有伦理问题，并以微创和安全的方式获得。然而，未分级的克隆源性DPSC是异质的，并且在其表型上具有变化。在这篇综述中，我们总结了DPSC亚群的进一步分离方法，包括免疫选择方法和粒细胞集落刺激因子（G-CSF）梯度动员方法用于治疗性临床应用。分离的DPSC亚群在体外表现出干细胞特性：（i）多能性标志物Oct 3/4、Nanog和Sox 2的高表达;（ii）长期扩增的高稳定性;（iii）多谱系分化能力;（iv）高迁移活性;和（v）营养因子的高表达以增强增殖，迁移，以及抗凋亡和免疫调节作用以及血管生成和神经突延伸。与骨髓干细胞和脂肪干细胞相比，DPSC亚群具有更高的血管生成，神经生成和再生潜力，为细胞治疗提供了替代的多功能干细胞来源。DPSC亚群的临床前疗效也已在各种组织/器官疾病模型（包括牙髓炎）中进行了研究，目前正在进行一些临床试验以确定其安全性和疗效。因此，本综述的主要目的是强调DPSC生物学的最新进展，临床前再生研究的趋势和未来的前景。
Dental pulp-derived stem cells (DPSCs) are considered to be of great promise for use in tissue repair and regenerative medicine. DPSCs can easily be collected from discarded teeth with little ethical concerns and harvested in a minimally invasive and safe manner. However, unfractionated clonogenic DPSCs are heterogenous and have variations in their phenotype. In this review paper, we summarize further isolation methods of DPSC subpopulations including immunoselection methods and a granulocyte colony-stimulating factor (G-CSF) gradient mobilization method for therapeutic clinical applications. The fractionated DPSC subpopulations exhibit stem cell properties in vitro: (i) high expression of pluripotency markers, Oct3/4, Nanog, and Sox2; (ii) high stability in long-term expansion; (iii) multi-lineage differentiation capacity; (iv) high migratory activity; and (v) high expression of trophic factors to enhance proliferation, migration, and anti-apoptotic and immunomodulatory effects as well as angiogenesis and neurite extension. DPSC subpopulations have higher angiogenic, neurogenic, and regenerative potential compared with bone marrow stem cells and adipose stem cells, presenting an alternate versatile stem cell source for cellular therapies. Preclinical efficacy of DPSC subpopulations has also been investigated in various tissue/organ disease models including pulpitis, and currently a few clinical trials are underway to determine their safety and efficacy. Therefore, the major aim of this review is to highlight the recent progress in DPSC biology, trends in preclinical regenerative studies, and future perspectives.