Chonglin Chen, Ting Zou, Qiyou Li, et al. Mitochondrial transfer from neural stem cells rescues apoptosis of retinal pigment epithelial cells isolated from RCS rats[J]. Journal of Third Military Medical University, 2017, 39(11): 1112-1116.
DOI:
Chonglin Chen, Ting Zou, Qiyou Li, et al. Mitochondrial transfer from neural stem cells rescues apoptosis of retinal pigment epithelial cells isolated from RCS rats[J]. Journal of Third Military Medical University, 2017, 39(11): 1112-1116. DOI: 10.16016/j.1000-5404.201701031.
Mitochondrial transfer from neural stem cells rescues apoptosis of retinal pigment epithelial cells isolated from RCS rats
摘要
Abstract
Objective
2
To investigate the pattern of mitochondrial transfer in neural stem cells (NSCs)and primary cultured retinal pigment epithelial (RPE) cells isolated from Royal College of Surgeons (RCS) rats and analyze the effect mitochondrial transfer on the biological behaviors of RPE cells.
Methods
2
The RPE cells were isolated from the RCS rats
cultured primarily and identified. Mitotracker-red and mitotracker-green staining were used to label the mitochondria of the cultured RPE cells and those of mouse neural stem cell line C17.2
respectively.In a co-culture system of the 2 kinds of cells
the formation of tunneling nanotubes (TNT) between them and mitochondrial transfer in the TNT were observed by laser scanning confocal microscopy. Flow cytometry was used to measure the level of reactive oxygen species (ROS) production and analyze the cell cycle distribution and early apoptosis of RPE cells cultured alone or in the co-culture system.
Results
2
The RPE cel
ls in the third generation showed a good growth condition with the positive rates for RPE65 and Bestrophin both exceeding 95%. At 24 h after the co-culture
the formation of TNT structure was observed between RPE cells and NSCs
and one-way mitochondrial transfer from NSCs to RPE cells were captured. Mitochondrial transfer from the NSCs to the RPE cells resulted in significantly decreased ROS level in the latter cells (
P
<
0.05). The RPE cells receiving the mitochondria also showed enhanced cell proliferation
increased cell proportion in S phase (
P
<
0.01)
elevated proliferation index (
P
<
0.05)
and decreased early apoptosis cells(
P
<
0.05).
Conclusion
2
In the co-culture system
NSCs transfer mitochondria into adjacent RPE cells
via
the TNT structure to rescues the RPE cells from apoptosis.
关键词
Keywords
references
Barot M Gokulgandhi M R Mitra A K Mitochondrial dysfunction in retinal diseases Curr Eye Res 2011 36 12 1069 1077 10.3109/02713683.2011.607536 Barot M, Gokulgandhi M R, Mitra A K.Mitochondrial dysfunction in retinal diseases[J]. Curr Eye Res, 2011, 36(12): 1069-1077. DOI: 10.3109/02713683.2011.607536.
Han H Hu J Yan Q Bone marrow-derived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model Mol Med Rep 2016 13 2 1517 1524 10.3892/mmr.2015.4726 Han H, Hu J, Yan Q, et al . Bone marrow-derived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model[J ] . Mol Med Rep, 2016, 13(2): 1517-1524. DOI:10.3892/mmr.2015.4726.
Li X Zhang Y Yeung S C Mitochondrial transfer of induced pluripotent stem cell-derived mesenchymal stem cells to airway epithelial cells attenuates cigarette smoke-induced damage Am J Respir Cell Mol Biol 2014 51 3 455 465 10.1165/rcmb.2013-0529OC Li X, Zhang Y, Yeung S C, et al . Mitochondrial transfer of induced pluripotent stem cell-derived mesenchymal stem cells to airway epithelial cells attenuates cigarette smoke-induced damage[J ] . Am J Respir Cell Mol Biol, 2014, 51(3): 455-465. DOI: 10.1165/rcmb.2013-0529OC.
Liu K Ji K Guo L Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer Microvasc Res 2014 92 10 18 10.1016/j.mvr.2014.01.008 Liu K, Ji K, Guo L, et al . Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer[J ] . Microvasc Res, 2014, 92: 10-18. DOI: 10.1016/j.mvr.2014.01.008.
Vallabhaneni K C Haller H Dumler I Vascular smooth muscle cells initiate proliferation of mesenchymal stem cells by mitochondrial transfer via tunneling nanotubes Stem CellDev 2012 21 17 3104 3113 10.1089/scd.2011.0691 Vallabhaneni K C, Hal ler H, Dumler I. Vascular smooth muscle cells initiate proliferation of mesenchymal stem cells by mitochondrial transfer via tunneling nanotubes[J ] . Stem CellDev, 2012, 21(17): 3104-3113. DOI: 10.1089/scd.2011.0691.
Blake R Trounce I A Mitochondrial dysfunction and complications associated with diabetes Biochim Biophys Acta 2014 1840 4 1404 1412 10.1016/j.bbagen.2013.11.007 Blake R, Trounce I A.Mitochondrial dysfunction and complications associated with diabetes[J]. Biochim Biophys Acta, 2014, 1840(4): 1404-1412. DOI: 10.1016/j.bbagen.2013.11.007.
Terluk M R Kapphahn R J Soukup L M Investigating mitochondria as a target for treating age-related macular degeneration J Neurosci 2015 35 18 7304 7311 10.1523/jneurosci.0190-15.2015 Terluk M R, Kapphahn R J, Soukup L M, et al . Investigating mitochondria as a target for treating age-related macular degeneration[J ] . J Neurosci, 2015, 35(18): 7304-7311. DOI: 10.1523/jneurosci.0190- 15.2015.
Schwartz S D Hubschman J P Heilwell G Embryonic stem cell trials for macular degeneration: a preliminary report Lancet 2012 379 9817 713 720 10.1016/s0140-6736(12)60028-2 Schwartz S D, Hubschman J P, Heilwell G, et al . Embryonic stem cell trials for macular degeneration: a preliminary report[J ] . Lancet, 2012, 379(9817):713-720. DOI: 10.1016/s0140-6736(12)60028-2.
Edwards R B The isolation and culturing of retinal pigment epithelium of the rat Vision Res 1981 21 1 147 150 10.1016/0042-6989(81)90149-8 Edwards R B. The isolation and culturing of retinal pigment epithelium of the rat[J]. Vision Res, 1981, 21(1): 147-150.
Nash M S Osborne N N Pertussis toxin-sensitive melatonin receptors negatively coupled to adenylate cyclase associated with cultured human and rat retinal pigment epithelial cells Invest Ophthalmol Vis Sci 1995 36 1 95 102 http://www.ncbi.nlm.nih.gov/pubmed/7822164 Nash M S, Osborne N N. Pertussis toxin-sensitive melatonin receptors negatively coupled to adenylate cyclase associated with cultured human and rat retinal pigment epithelial cells[J]. Invest Ophthalmol Vis Sci, 1995, 36(1): 95-102.
De FeoD Merlini A Laterza C Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection Curr Opin Neurol 2012 25 3 322 333 10.1097/WCO.0b013e328352ec45 De FeoD, Merlini A, Laterza C, et al .Neural stem cell transplantation in central nervous system disorders: from cell replacement to neuroprotection[J ] . Curr Opin Neurol, 2012, 25(3): 322-333. DOI: 10.1097/WCO.0b013e328352ec45.
Rustom A Saffrich R Markovic I Nanotubular highways for intercellular organelle transport Science 2004 303 5660 1007 1010 10.1126/science.1093133 Rustom A, Saffrich R, Markovic I, et al . Nanotubular highways for intercellular organelle transport[J ] . Science, 2004, 303(5660):1007-1010. DOI: 10.1126/science.1093133.
Austefjord M W Gerdes H H Wang X Tunneling nanotubes: Diversity in morphology and structure Commun Integr Biol 2014 7 1 e27934 10.4161/cib.27934 Austefjord M W, Gerdes H H, Wang X.Tunneling nanotubes: Diversity in morphology and structure[J]. Commun Integr Biol, 2014, 7(1): e27934. DOI: 10.4161/cib.27934.
Hase K Kimura S Takatsu H M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex Nat Cell Biol 2009 11 12 1427 1432 10.1038/ncb1990 Hase K, Kimura S, Takatsu H, et al . M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex[J ] . Nat Cell Biol, 2009, 11(12): 1427-1432. DOI: 10.1038/ncb1990.
Onfelt B Nedvetzki S Yanagi K Cutting edge: Membrane nanotubes connect immune cells J Immunol 2004 173 3 1511 1513 10.4049/jimmunol.173.3.1511 Onfelt B, Nedvetzki S, Yanagi K, et al . Cutting edge: Membrane nanotubes connect immune cells[J ] . J Immunol, 2004, 173(3): 1511-1513.
Gurke S Barroso J F Gerdes H H The art of cellular communication: tunneling nanotubes bridge the divide Histochem Cell Biol 2008 129 5 539 550 10.1007/s00418-008-0412-0 Gurke S, Barroso J F, Gerdes H H. The art of cellular communication: tunneling nanotubes bridge the divide[J].Histochem Cell Biol, 2008, 129(5): 539-550. DOI: 10.1007/s00418-008-0412-0.
D'Cruz P M Yasumura D Weir J Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat Hum Mol Genet 2000 9 4 645 651 10.1093/hmg/9.4.645 D'Cruz P M, Yasumura D, Weir J, et al . Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat[J ] . Hum Mol Genet, 2000, 9(4): 645-651.
Nandrot E F Dufour E M Mertk in daily retinal phagocytosis: a history in the making Adv Exp Med Biol 2010 664 133 140 10.1007/978-1-4419-1399-9_16 Nandrot E F, Dufour E M. Mertk in daily retinal phagocytosis: a history in the making[J].Adv Exp Med Biol, 2010, 664: 133-140. DOI: 10.1007/978-1-4419-1399-9_16.
Effect of TNTs-mediated mitochondrial transfer between mesenchymal stem cells and endothelial cells on vascularization in vitro
Chronic hypoxia reduces cold tolerance via hepatic ANGPTL3-driven mitochondrial damage and adipose thermogenesis suppression
Z-Ligustilide ameliorates retinitis pigmentosa via inhibiting PI3K/AKT-inflammation axis: Validation based on network pharmacology and molecular docking
Palmitic acid increases apoptosis by mitochondrial pathway in hepatocytes with growth hormone deficiency
Effects of direct current electric field on proliferation and biological characteristics of human adipose derived mesenchymal stem cells
Related Author
Yunying HE
Hua ZHANG
Ping JI
HUANG Yujie
HUANG Lingfang
ZHEGN Minghai
XIONG Kun
TAN Xiaoling
Related Institution
Department of Obstetrics and Gynaecology, the First Affiliated Hospital of Chongqing Medical University
Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Key Laboratory of Oral Biomedical Engineering of Higher Education, College of Stomatology, Chongqing Medical University
Department of Clinical Nursing, School of Nursing, Army Medical University (Third Military Medical University)
Key Laboratory of Extreme Environmental Medicine of Ministry of Education, School of Nursing, Army Medical University (Third Military Medical University)
Department of Frigid Zone Medicine, College of High Altitude Military Medicine, School of Nursing, Army Medical University (Third Military Medical University)