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Regenerative medicine for musclo-skeltal system using autologous mesenchymal stem cell conjugated with magnet beads or magnet liposome

使用与磁珠或磁脂质体缀合的自体间充质干细胞进行肌肉骨骼系统的再生医学

基本信息

批准号：
16209045
负责人：
OCHI Mitsuo
金额：
$ 32.2万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

The purpose of this research project was to establish new cell delivery system using magnetically labeled cells and external magnetic device heading for future clinical application. We have used several different cells such as mesenchymal stem cells (MSC) from bone marrow, neural progenitor cells, or natural killer cells as cell source.First, we have established methods to label those cells magnetically using liposome, magnetic beads, or Ferumoxides ((Fe_2O_3)_n (FeO)_m). We also made an external magnetic device, which can be used for human clinical application.As for in vivo study for cartilage regeneration using this cell delivery system, we made osteochondral defects in the swine patella and injected magnetically labeled MSC under influence of external magnet force. We confirmed that the injected magnetically labeled cells were accumulated to the cartilage defect of the patella against gravity even 90 minutes after magnetic force application. In vitro study, we accumulated those magnetically labeled MSC on the degenerated cartilage piece taken from osteoarthritic knee using this cell delivery system. Then, those accumulated cells attached to the cartilage piece were cultured for 3 weeks in chondrogenic differentiation medium. After 3 weeks of culture, cartilage-like layers were formed on the degenerated cartilage piece indicating cartilage regeneration using this cell delivery system.Beside several researches for cartilage regeneration, we have established cell delivery system for spinal cord injury, bone defect, or malignant tumor. The results of those researches were all positive and were published in international journals, which have high impact factors.

本研究旨在利用磁标记细胞和外磁装置建立一种新的细胞递送系统，为将来的临床应用打下基础。我们使用了几种不同的细胞作为细胞源，如骨髓间充质干细胞（MSC）、神经祖细胞或自然杀伤细胞。首先，我们建立了用脂质体、磁珠或氧化铁(（Fe_2O_3)_n (FeO)_m）对这些细胞进行磁性标记的方法。我们还制作了一种可用于人体临床的外磁装置。在体外研究中，我们在猪髌骨上制造骨软骨缺损，并在外加磁力的作用下注射磁性标记的间充质干细胞。我们证实，即使在施加磁力90分钟后，注射的磁性标记细胞仍在重力作用下积聚到髌骨软骨缺损处。在体外研究中，我们使用这种细胞递送系统将这些磁性标记的间充质干细胞积累在骨关节炎膝关节退变软骨片上。将积累的细胞附着在软骨片上，在软骨分化培养基中培养3周。培养3周后，在退变的软骨片上形成软骨样层，表明该细胞递送系统使软骨再生。除了软骨再生的研究外，我们还建立了脊髓损伤、骨缺损、恶性肿瘤的细胞递送系统。这些研究结果都是正面的，并且发表在国际期刊上，影响因子高。