Therapeutic Potential of Stem Cells from Human Exfoliated Deciduous Teeth in Models of Acute Kidney Injury

被引:29
作者
Hattori, Yuka [1 ]
Kim, Hangsoo [2 ]
Tsuboi, Naotake [2 ]
Yamamoto, Akihito [1 ]
Akiyama, Shinichi [2 ]
Shi, Yiqin [2 ]
Katsuno, Takayuki [2 ]
Kosugi, Tomoki [2 ]
Ueda, Minoru [1 ]
Matsuo, Seiichi [2 ]
Maruyama, Shoichi [2 ]
机构
[1] Nagoya Univ, Grad Sch Med, Dept Oral & Maxillofacial Surg, Showa Ku, Nagoya, Aichi 466, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Nephrol, Showa Ku,Internal Med, Nagoya, Aichi 466, Japan
关键词
ISCHEMIA-REPERFUSION INJURY; ACUTE-RENAL-FAILURE; TUBULAR EPITHELIAL-CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; HEPATOCYTE GROWTH-FACTOR; STROMAL CELLS; DENTAL-PULP; BONE-MARROW; ADIPOSE-TISSUE; EXTRACELLULAR VESICLES;
D O I
10.1371/journal.pone.0140121
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Acute kidney injury (AKI) is a critical condition associated with high mortality. However, the available treatments for AKI are limited. Stem cells from human exfoliated deciduous teeth (SHED) have recently gained attention as a novel source of stem cells. The purpose of this study was to clarify whether SHED have a therapeutic effect on AKI induced by ischemia-reperfusion injury. Methods The left renal artery and vein of the mice were clamped for 20 min to induce ischemia. SHED, bone marrow derived mesenchymal stem cells (BMMSC) or phosphate-buffered saline (control) were administered into the subrenal capsule. To confirm the potency of SHED in vitro, H2O2 stimulation assays and scratch assays were performed. Results The serum creatinine and blood urea nitrogen levels of the SHED group were significantly lower than those of the control group, while BMMSC showed no therapeutic effect. Infiltration of macrophages and neutrophils in the kidney was significantly attenuated in mice treated with SHED. Cytokine levels (MIP-2, IL-1 beta, and MCP-1) in mice kidneys were significantly reduced in the SHED group. In in vitro experiments, SHED significantly decreased MCP-1 secretion in tubular epithelial cells (TEC) stimulated with H2O2. In addition, SHED promoted wound healing in the scratch assays, which was blunted by anti-HGF antibodies. Discussion SHED attenuated the levels of inflammatory cytokines and improved kidney function in AKI induced by IRI. SHED secreted factors reduced MCP-1 and increased HGF expression, which promoted wound healing. These results suggest that SHED might provide a novel stem cell resource, which can be applied for the treatment of ischemic kidney injury.
引用
收藏
页数:18
相关论文
共 59 条
[1]   Pharmacokinetics and Pharmacodynamics following Intravenous Administration of Recombinant Human Hepatocyte Growth Factor in Rats with Renal Injury [J].
Adachi, Eri ;
Hirose-Sugiura, Tomoko ;
Kato, Yukio ;
Ikebuchi, Fumie ;
Yamashita, Atsuko ;
Abe, Tetsushi ;
Fukuta, Kazuhiro ;
Adachi, Kiichi ;
Matsumoto, Kunio .
PHARMACOLOGY, 2014, 94 (3-4) :190-197
[2]   Stromal cells protect against acute tubular injury via an endocrine effect [J].
Bi, Baoyuan ;
Schmitt, Roland ;
Israilova, Malika ;
Nishio, Hitoshi ;
Cantley, Lloyd G. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 18 (09) :2486-2496
[3]   Ischemic acute renal failure: An inflammatory disease? [J].
Bonventre, JV ;
Zuk, A .
KIDNEY INTERNATIONAL, 2004, 66 (02) :480-485
[4]   Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats [J].
Broekema, M ;
Harmsen, MC ;
Koerts, JA ;
Petersen, AH ;
van Luyn, MJA ;
Navis, G ;
Popa, ER .
KIDNEY INTERNATIONAL, 2005, 68 (06) :2572-2581
[5]   Role of mesenchymal stem cell-derived microvesicles in tissue repair [J].
Bruno, Stefania ;
Camussi, Giovanni .
PEDIATRIC NEPHROLOGY, 2013, 28 (12) :2249-2254
[6]   Mesenchymal Stem Cell-Derived Microvesicles Protect Against Acute Tubular Injury [J].
Bruno, Stefania ;
Grange, Cristina ;
Deregibus, Maria Chiara ;
Calogero, Raffaele A. ;
Saviozzi, Silvia ;
Collino, Federica ;
Morando, Laura ;
Busca, Alessandro ;
Falda, Michele ;
Bussolati, Benedetta ;
Tetta, Ciro ;
Camussi, Giovanni .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (05) :1053-1067
[7]   Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction [J].
Chen, Yen-Ta ;
Sun, Cheuk-Kwan ;
Lin, Yu-Chun ;
Chang, Li-Teh ;
Chen, Yung-Lung ;
Tsai, Tzu-Hsien ;
Chung, Sheng-Ying ;
Chua, Sarah ;
Kao, Ying-Hsien ;
Yen, Chia-Hong ;
Shao, Pei-Lin ;
Chang, Kuan-Cheng ;
Leu, Steve ;
Yip, Hon-Kan .
JOURNAL OF TRANSLATIONAL MEDICINE, 2011, 9
[8]   Dental pulp stem cells: A promising tool for bone regeneration [J].
d'Aquino, Riccardo ;
Papaccio, Gianpaolo ;
Laino, Gregorio ;
Graziano, Antonio .
STEM CELL REVIEWS, 2008, 4 (01) :21-26
[9]   Proliferation of bone marrow-derived cells contributes to regeneration after folic acid-induced acute tubular injury [J].
Fang, TC ;
Alison, MR ;
Cook, HT ;
Jeffery, R ;
Wright, NA ;
Poulsom, R .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (06) :1723-1732
[10]   Serum-Starved Adipose-Derived Stromal Cells Ameliorate Crescentic GN by Promoting Immunoregulatory Macrophages [J].
Furuhashi, Kazuhiro ;
Tsuboi, Naotake ;
Shimizu, Asuka ;
Katsuno, Takayuki ;
Kim, Hangsoo ;
Saka, Yosuke ;
Ozaki, Takenori ;
Sado, Yoshikazu ;
Imai, Enyu ;
Matsuo, Seiichi ;
Maruyama, Shoichi .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 24 (04) :587-603