Differentiation of Dermal Multipotent Cells Into Odontogenic Lineage Induced by Embryonic and Neonatal Tooth Germ Cell-Conditioned Medium
Differentiation of Dermal Multipotent Cells Into Odontogenic Lineage Induced by Embryonic and Neonatal Tooth Germ Cell-Conditioned Medium
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DOI：
10.1089/scd.2009.0048
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Jin, Yan
中科院分区：
文献类型：
--
作者：
Huo, Na;Tang, Liang;Jin, Yan
基于干细胞的治疗代表了治疗牙齿缺损或缺失的一种新的和更有利的方式。然而，这种策略在牙齿来源的干细胞不易获得的情况下受到挑战。在本研究中，我们试图探索利用容易从皮肤组织中获得的真皮多能细胞（DMCs）进行牙源性诱导的可能性。采用有限稀释法分离集落形成细胞群，并以增殖活性和多向分化潜能为特征。胚胎和新生牙胚细胞条件培养液均能促进牙胚干细胞的增殖和矿化活性，其中胚胎牙胚细胞条件培养液（ETGC-CM）的作用更为显著。同时，ETGC-CM处理的DMCs在体外表型模仿成牙本质细胞，如特定的谱系标记所示。作为细胞团在体内移植后，ETGC-CM处理的DMC能够产生矿化组织块，其类似于在相同皮下袋环境中的牙髓干细胞（DPSC）外植体。这些观察结果表明，尽管未分化的DMCs可能需要更充分和连续的诱导微环境才能发挥成牙本质细胞的作用，但ETGC-CM处理的DMCs确实获得了DPSC的特性。我们的工作突出了DMCs作为替代候选细胞来源的潜在效用，希望开发更实用的牙齿再生研究策略，并为治疗方法提供有希望的机会。
Stem cell-based therapy represents a novel and more advantageous modality of treatment for tooth defect or loss. However, this strategy is challenged in the circumstances where tooth-derived stem cells are not readily accessible. In present study we sought to explore the possibility of utilizing dermal multipotent cells (DMCs) easily available from skin tissue for odontogenic induction. Using the limiting dilution technique, colony-forming cell population was isolated and characterized by proliferative activity and multilineage differentiation potential. By exposure to conditioned medium of embryonic and neonatal tooth germ cells in culture, the proliferation and mineralization activity of DMCs was elevated, while the embryonic tooth germ cell-conditioned medium (ETGC-CM) produced more significant effects. Meanwhile, ETGC-CM-treated DMCs phenocopied the odontoblasts in vitro as indicated by specific lineage markers. Following in vivo transplantation as cell pellet, ETGC-CM-treated DMCs were capable of producing blocks of mineralized tissues, which resembled those of dental pulp stem cell (DPSC) explants in the same subcutaneous pockets environment. These observations suggest that although more sufficient and continuous inductive microenvironment may be needed for undifferentiated DMCs to perform as odontoblasts, ETGC-CM-treated DMCs indeed acquire properties as those of DPSCs. Our work highlights the potential utility of DMCs as an alternative candidate cell source in hopes of developing more practical strategy of tooth regeneration research and offering promising opportunities for therapeutic approach.