Tong Jia-Bei, Wu Xiao-Yun, Jia Ge-Liuchang, Zhao Kui-Jun, Wang Shi-Li, Ma Zhi-Jie
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Xicheng District, Beijing 100050, China ; Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, 18877 Jingshi Road, Jinan 250000, China.
Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Modern Medicine and Technology of Shandong Province, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Laboratory for Virology of Shandong Province, Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, 18877 Jingshi Road, Jinan 250000, China ; Department of Technology, Beijing Jingmeng Stem Cell Technology Co., Ltd., 5-2 Shangdi East Road, Beijing 100085, China.
Biomed Res Int. 2015;2015:398642. doi: 10.1155/2015/398642. Epub 2015 Jan 28.
Hematopoietic stem and progenitor cells (HSPCs) have been used successfully to treat patients with cancer and disorders of the blood and immune systems. In this study, we tried to enrich HSPCs by implanting biomaterials into the spatium intermusculare of mice hind limbs. Gelatine sponges were implanted into the spatium intermusculare of mice and then retrieved after 12 days. The presence of HSPCs in the migrating cells (MCs) was detected by phenotypically probing with CD34(+)Sca-1(+) and functionally confirming the presence of using colony-forming cell assay and assessing the long-term reconstitution ability. The frequency of CD34(+), Sca-1(+), and CD34(+)Sca-1(+) cells and colony formation unit in the MCs was much higher than that in the bone marrow (BM). Moreover, transplanted MCs were able to home to BM, muscle, and spleen, which induced an efficient long-term hematopoietic reconstitution in vivo. In addition, HSPCs within the MCs originated from the BM. Furthermore, the administration of G-CSF greatly reduced the time of implantation, and increased the number of MCs and frequency of HSPCs in the MCs. These data provide compelling evidence that HSPCs can be enriched by implanting biomaterial into spatium intermusculare. Implantation of biomaterial may be seen as the first step to a proof of their applicability to clinical practice in enriching HSPCs.
造血干细胞和祖细胞(HSPCs)已成功用于治疗癌症患者以及血液和免疫系统疾病患者。在本研究中,我们尝试通过将生物材料植入小鼠后肢肌间隙来富集HSPCs。将明胶海绵植入小鼠肌间隙,12天后取出。通过用CD34(+)Sca-1(+)进行表型探测,并通过集落形成细胞测定功能确认其存在以及评估长期重建能力,来检测迁移细胞(MCs)中HSPCs的存在。MCs中CD34(+)、Sca-1(+)和CD34(+)Sca-1(+)细胞的频率以及集落形成单位远高于骨髓(BM)中的频率。此外,移植的MCs能够归巢到骨髓、肌肉和脾脏,在体内诱导高效的长期造血重建。另外,MCs中的HSPCs起源于骨髓。此外,给予粒细胞集落刺激因子(G-CSF)大大缩短了植入时间,并增加了MCs的数量以及MCs中HSPCs的频率。这些数据提供了令人信服的证据,表明通过将生物材料植入肌间隙可以富集HSPCs。生物材料的植入可被视为证明其在富集HSPCs方面应用于临床实践的第一步。