Enhanced Healing of Rat Calvarial Bone Defects with Hypoxic Conditioned Medium from Mesenchymal Stem Cells through Increased Endogenous Stem Cell Migration via Regulation of ICAM-1 Targeted-microRNA-221

被引:32
作者
Chang, Woochul [2 ]
Kim, Ran [2 ]
Park, Sang In [1 ]
Jung, Yu Jin [3 ]
Ham, Onju [4 ]
Lee, Jihyun [2 ]
Kim, Ji Hyeong [2 ]
Oh, Sekyung [5 ]
Lee, Min Young [6 ]
Kim, Jongmin [7 ]
Park, Moon-Seo [2 ]
Chung, Yong-An [1 ]
Hwang, Ki-Chul [8 ,9 ]
Maeng, Lee-So [1 ]
机构
[1] Catholic Univ Korea, Coll Med, Incheon St Marys Hosp, Inst Catholic Integrat Med, Inchon 403720, South Korea
[2] Pusan Natl Univ, Coll Educ, Dept Biol Educ, Busan 609735, South Korea
[3] Catholic Kwandong Univ, Int St Marys Hosp, EIT LOFUS Res Ctr, Inchon 404834, South Korea
[4] Yonsei Univ, Coll Med, Brain Korea PLUS Project Med Sci 21, Seoul 120752, South Korea
[5] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA
[6] Kyungpook Natl Univ, Coll Pharm, Dept Mol Physiol, Taegu 702701, South Korea
[7] Sookmyung Womens Univ, Dept Life Syst, Seoul 140742, South Korea
[8] Catholic Kwandong Univ, Coll Med, Inst Biomed Convergence, Gangwon 210701, South Korea
[9] Catholic Kwandong Univ Int, St Marys Hosp, Inchon 404834, South Korea
基金
新加坡国家研究基金会;
关键词
bone regeneration; calvarial defect model; hypoxic conditioned medium; intercellular adhesion molecule-1; mesenchymal stem cells; microRNA-221; ENDOTHELIAL-CELLS; REPAIR; ADHESION; ANGIOGENESIS; REGENERATION; CANCER; DIFFERENTIATION; ACTIVATION; MECHANISMS; EXPRESSION;
D O I
10.14348/molcells.2015.0050
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.
引用
收藏
页码:643 / 650
页数:8
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