Adipose-derived stromal cells grown on a hydroxyapatite scaffold can support hematopoiesis in regenerated bone marrow in vivo.
Adipose-derived stromal cells grown on a hydroxyapatite scaffold can support hematopoiesis in regenerated bone marrow in vivo.
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在羟基磷灰石支架上生长的脂肪源性基质细胞可以支持体内再生骨髓的造血作用。
DOI：
10.1002/cbin.10254
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
MigitaM.
中科院分区：
文献类型：
--
作者：
Ueda T;Fujita A;Ogawa R;Itoh Y;Fukunaga Y;Shimada T;MigitaM.
成骨细胞是骨髓(BM)干细胞生态位的关键组成部分，有助于调节造血干细胞(HSCs)。我们先前已经证明脂肪来源的基质细胞(ADSCs)在体外可以分化为成骨细胞和软骨细胞。目前的研究检测了利用培养在羟基磷灰石(HA)支架上的ADSCs能否在体内再生BM的解剖结构。将绿色荧光蛋白转基因小鼠的脂肪干细胞体外培养于透明质酸支架上。将附着细胞的支架植入C57/BL6(Ly5.2)受体小鼠背部皮下。用含有荧光素酶(Luc)基因的慢病毒载体转导LIN-LY5.1 BM细胞，在接受致死性照射后静脉注射给药。骨髓移植8周后，从第一只受体小鼠身上取出支架，并将其植入受到致死性照射的第二只受体小鼠的皮下。通过生物发光成像和流式细胞仪检测Luc+Ly5.1细胞的生物分布和动力学。二次植入的小鼠支架内存在Luc+造血细胞至少8个月。皮下注射G-CSF导致生物发光信号从原始支架广泛分布到全身。因此，使用生长在HA支架上的ADSCs再生的BM可以支持体内的HSC群体，这表明一个功能性的BM生态位被重建。这些结果可能会对各种血液系统疾病的治疗策略的发展产生重大影响。
Osteoblastic cells are a key component of the bone marrow (BM) stem cell niche and help regulate hematopoietic stem cells (HSCs). We have previously demonstrated that adipose‐derived stromal cells (ADSCs) can differentiate into both osteogenic and chondrogenic cells in vitro. The current study examined whether the anatomical architecture of the BM could be regenerated in vivo by using ADSCs cultured on a hydroxyapatite (HA) scaffold. ADSCs from GFP transgenic mice were cultured in vitro on an HA scaffold. The scaffold with the attached cells was implanted subcutaneously onto the backs of C57/BL6 (Ly5.2) recipient mice. Lineage‐negative (Lin‐) Ly5.1 BM cells transduced with a lentiviral vector containing the luciferase (Luc) gene were intravenously administered to the recipient mice after lethal irradiation. Eight weeks after BM transplantation, the scaffolds were removed from the first recipient mice and subcutaneously implanted into lethally irradiated second recipient mice. The biodistribution and kinetics of Luc+Ly5.1 cells were monitored by bioluminescence imaging and flow cytometry. Luc+hematopoietic cells were present in the scaffolds of the secondary implanted mice for at least 8 months. Subcutaneous injection of G‐CSF resulted in wide distribution of bioluminescence signals from the original scaffolds to the whole body. Therefore, BM regenerated using ADSCs grown on an HA scaffold can support HSC populations in vivo, suggesting that a functional BM niche is reconstituted. These results may have a significant impact on the development of therapeutic strategies for various hematopoietic diseases.