The use of granulocyte-colony stimulating factor induced mobilization for isolation of dental pulp stem cells with high regenerative potential

被引:100
作者
Murakami, Masashi [1 ]
Horibe, Hiroshi [1 ,2 ]
Iohara, Koichiro [1 ]
Hayashi, Yuki [1 ,3 ]
Osako, Yohei [1 ]
Takei, Yoshifumi [4 ,5 ]
Nakata, Kazuhiko [6 ]
Motoyama, Noboru [7 ]
Kurita, Kenichi [2 ]
Nakashima, Misako [1 ]
机构
[1] Natl Ctr Geriatr & Gerontol, Dept Dent Regenerat Med, Ctr Adv Med Dent & Oral Dis, Res Inst, Obu, Aichi 4748511, Japan
[2] Aichi Gakuin Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Nagoya, Aichi 464, Japan
[3] Aichi Gakuin Univ, Sch Dent, Dept Pediat Dent, Nagoya, Aichi 464, Japan
[4] Nagoya Univ, Dept Biochem, Grad Sch Med, Ctr Neurol Dis & Canc, Nagoya, Aichi 4648601, Japan
[5] Nagoya Univ, Div Dis Models, Grad Sch Med, Ctr Neurol Dis & Canc, Nagoya, Aichi 4648601, Japan
[6] Aichi Gakuin Univ, Sch Dent, Dept Endodont, Nagoya, Aichi 464, Japan
[7] Natl Ctr Geriatr & Gerontol, Dept Cognit Brain Sci, Res Inst, Obu, Aichi 4748511, Japan
关键词
Dental pulp stem/progenitor cells; Granulocyte-colony stimulating factor (G-CSF); Trophic effect; Migration; Angiogenesis/vasculogenesis; Pulp regeneration; SIDE POPULATION CELLS; BONE-MARROW; STEM/PROGENITOR CELLS; DIFFERENTIATE; ANGIOGENESIS; EXPRESSION; PULPECTOMY; MIGRATION; ISCHEMIA; RECOVERY;
D O I
10.1016/j.biomaterials.2013.08.011
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
Human dental pulp stem cells (DPSCs) contain subsets of progenitor/stem cells with high angiogenic, neurogenic and regenerative potential useful for cell therapy. It is essential to develop a safe and efficacious method to isolate the clinical-grade DPSCs subsets from a small amount of pulp tissue without using conventional flow cytometry. Thus, a method for isolation of DPSCs subsets based on their migratory response to optimized concentration of 100 ng/ml of granulocyte-colony stimulating factor (G-CSF) was determined in this study. The DPSCs mobilized by G-CSF (MDPSCs) were enriched for CD105, CX-C chemokine receptor type 4 (CXCR-4) and G-CSF receptor (G-CSFR) positive cells, demonstrating stem cell properties including high proliferation rate and stability. The absence of abnormalities/aberrations in karyotype and lack of tumor formation after transplantation in an immunodeficient mouse were demonstrated. The conditioned medium of MDPSCs exhibited anti-apoptotic activity, enhanced migration and immunomodulatory properties. Furthermore, transplantation of MDPSCs accelerated vasculogenesis in an ischemic hindlimb model and augmented regenerated pulp tissue in an ectopic tooth root model compared to that of colony-derived DPSCs, indicating higher regenerative potential of MDPSCs. In conclusion, this isolation method for DPSCs subsets is safe and efficacious, having utility for potential clinical applications to autologous cell transplantation. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:9036 / 9047
页数:12
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