Mouse Dental Pulp Stem Cells Support Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells in Vitro
Mouse Dental Pulp Stem Cells Support Human Umbilical Cord Blood-Derived Hematopoietic Stem/Progenitor Cells in Vitro
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DOI：
10.3727/096368913x674675
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发表时间：
2015-01
影响因子：
3.3
通讯作者：
Ryusuke Nakatsuka;Yoshikazu Matsuoka;Y. Uemura;Keisuke Sumide;Ryuji Iwaki;Masaya Takahashi;T. Fujioka;Yutaka Sasaki;Y. Sonoda
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文献类型：
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作者：
Ryusuke Nakatsuka;Yoshikazu Matsuoka;Y. Uemura;Keisuke Sumide;Ryuji Iwaki;Masaya Takahashi;T. Fujioka;Yutaka Sasaki;Y. Sonoda
有充分的证据表明，特化的间充质干细胞/基质细胞（MSC）构成骨髓（BM）中的造血干细胞（HSC）小生境，并且这些MSC支持/维持HSC处于未分化状态。大量研究表明，骨髓间充质干细胞（BM-MSCs）可以在体外支持造血干细胞。然而，目前尚不清楚非造血组织来源的MSC样细胞，如牙髓干细胞（DPSC），是否有能力支持HSC。在这项研究中，我们使用BM-MSC标记物，如PDGFRα和Sca-1，通过荧光激活细胞分选术（FACS）从小鼠下颌切牙中前瞻性地分离DPSCs。PDGFRα和Sca-1双阳性的DPSC和BM-MSCs表现出相似的形态学和MSC标志物的表达模式。然后通过体外共培养系统分析DPSC支持造血干/祖细胞（HSPC）的能力。此外，通过使用NOD/Shi-scid/IL-2 R γcnull（NOG）小鼠的体内异种移植测定来评估它们的HSC支持活性。有趣的是，DPSC支持人脐带血（CB）来源的CD 34阳性（CD 34+）以及CD 34阴性（CD 34-）HSC。DPSC对人CB衍生的CD 34+和CD 34-HSC的支持活性与BM-MSC的那些相当。本研究的结果首次证明，前瞻性分离的小鼠PDGFRα和Sca-1双阳性DPSC可以在体外支持原始人CD 34+和CD 34-HSC。
It is well documented that specialized mesenchymal stem/stromal cells (MSCs) constitute the hematopoietic stem cell (HSC) niche in the bone marrow (BM), and these MSCs support/maintain the HSCs in an undifferentiated state. A number of studies have demonstrated that BM-derived MSCs (BM-MSCs) can support HSCs in vitro. However, it remains unclear whether nonhematopoietic tissue-derived MSC-like cells, such as dental pulp stem cells (DPSCs), have the ability to support HSCs. In this study, we prospectively isolated DPSCs from mouse mandibular incisors by fluorescence-activated cell sorting (FACS) using BM-MSC markers, such as PDGFRα and Sca-1. The PDGFRα and Sca-1 double-positive DPSCs and BM-MSCs showed similar morphologies and expression patterns of MSC markers. The ability of the DPSCs to support hematopoietic stem/progenitor cells (HSPCs) was then analyzed by an in vitro coculture system. Moreover, their HSC-supporting activity was evaluated by in vivo xenotransplantation assays using NOD/Shi-scid/IL-2Rγcnull (NOG) mice. Interestingly, the DPSCs supported human cord blood (CB)-derived CD34-positive (CD34+), as well as CD34-negative (CD34–), HSCs. The supporting activities of DPSCs for human CB-derived CD34+ and CD34– HSCs were comparable to those of BM-MSCs. The results of the present study demonstrated, for the first time, that prospectively isolated murine PDGFRα and Sca-1 double-positive DPSCs could support primitive human CD34+ and CD34– HSCs in vitro.