间充质干细胞归巢的研究与进展
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摘要
背景:间充质干细胞是一种低免疫原性的成体干细胞,具有多向分化潜能,已广泛应用于干细胞移植、免疫治疗、组织工程等各个领域。目的:综述间充质干细胞归巢机制及促进间充质干细胞归巢策略的研究新进展,为安全、高效间充质干细胞移植提供理论依据。方法:检索CNKI数据库和Pub Med数据库的相关文献,中文检索词为"间充质干细胞,归巢",英文检索词为"mesenchymal stem cells(MSCs),homing"。查阅2000至2016年间充质干细胞归巢研究的相关文献,包括综述、基础研究和临床研究,最终纳入74篇文献。结果与结论:间充质干细胞的归巢研究仍需要进一步探索,尤其是间充质干细胞动员的分子机制。因此,需要进一步深入开展间充质干细胞的基础研究,建立体外细胞归巢体系,开展间充质干细胞及转基因后移植的体内效应研究等均具有重要的意义。
BACKGROUND: As a kind of adult stem cells with low immunogenicity, mesenchymal stem cells are able to differentiate into different cell lineages in the treatment of many diseases. Moreover, mesenchymal stem cells have been extensively used in many fields such as stem cell transplantation, immune therapy, and tissue engineering. OBJECTIVE: To review the progress of homing mechanism and the strategies to promote mesenchymal stem cell homing, thus providing a theoretical basis for transplanting mesenchymal stem cells safely and efficiently. METHODS: The CNKI and Pub Med databases were retrieved by computer for articles regarding mesenchymal stem cell homing published from 2000 to 2016, including reviews, basic and clinical studies. The key words were "mesenchymal stem cells, homing" in Chinese and English, respectively. Then 74 papers were suitable for final analysis. RESULTS AND CONCLUSION: Mesenchymal stem cell homing needs further research, especially the molecular mechanism of cell mobilization. Therefore, basic research about mesenchymal stem cells should be further developed, and a standardized homing system should be established in vitro. In addition, it is of great significance to study the in vivo effects of transplanted gene-transfected mesenchymal stem cells.
BACKGROUND: As a kind of adult stem cells with low immunogenicity, mesenchymal stem cells are able to differentiate into different cell lineages in the treatment of many diseases. Moreover, mesenchymal stem cells have been extensively used in many fields such as stem cell transplantation, immune therapy, and tissue engineering. OBJECTIVE: To review the progress of homing mechanism and the strategies to promote mesenchymal stem cell homing, thus providing a theoretical basis for transplanting mesenchymal stem cells safely and efficiently. METHODS: The CNKI and Pub Med databases were retrieved by computer for articles regarding mesenchymal stem cell homing published from 2000 to 2016, including reviews, basic and clinical studies. The key words were "mesenchymal stem cells, homing" in Chinese and English, respectively. Then 74 papers were suitable for final analysis. RESULTS AND CONCLUSION: Mesenchymal stem cell homing needs further research, especially the molecular mechanism of cell mobilization. Therefore, basic research about mesenchymal stem cells should be further developed, and a standardized homing system should be established in vitro. In addition, it is of great significance to study the in vivo effects of transplanted gene-transfected mesenchymal stem cells.
引文
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[3]Erices A,Conget P,Minguell JJ.Mesenchymal progenitor cells in human umbilical cord blood.Br J Haematol.2000;109(1):235-242.
[4]Sacchetti B,Funari A,Michienzi S,et al.Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.Cell.2007;131(2):324-336.
[5]Dietz AB,Padley DJ,Gastineau DA.Infrastructure development for human cell therapy translation.Clin Pharmacol Ther.2007;82(3):320-324.
[6]Karp JM,Leng Teo GS.Mesenchymal stem cell homing:the devil is in the details.Cell Stem Cell.2009;4(3):206-216.
[7]Fekete N,Rojewski MT,Fürst D,et al.GMP-compliant isolation and large-scale expansion of bone marrow-derived MSC.PLo S One.2012;7(8):e43255.
[8]Woodbury D,Schwarz EJ,Prockop DJ,et al.Adult rat and human bone marrow stromal cells differentiate into neurons.J Neurosci Res.2000;61(4):364-370.
[9]Di Nicola M,Carlo-Stella C,Magni M,et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.Blood.2002;99(10):3838-3843.
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[11]Krampera M,Glennie S,Dyson J,et al.Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide.Blood.2003;101(9):3722-3729.
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[13]Nixon AJ,Goodrich LR,Scimeca MS,et al.Gene therapy in musculoskeletal repair.Ann N Y Acad Sci.2007;1117:310-327.
[14]Karp JM,Leng Teo GS.Mesenchymal stem cell homing:the devil is in the details.Cell Stem Cell.2009;4(3):206-216.
[15]Ringe J,Strassburg S,Neumann K,et al.Towards in situ tissue repair:human mesenchymal stem cells express chemokine receptors CXCR1,CXCR2 and CCR2,and migrate upon stimulation with CXCL8 but not CCL2.J Cell Biochem.2007;101(1):135-146.
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[17]Forte G,Minieri M,Cossa P,et al.Hepatocyte growth factor effects on mesenchymal stem cells:proliferation,migration,and differentiation.Stem Cells.2006;24(1):23-33.
[18]Cui Y,Madeddu P.The role of chemokines,cytokines and adhesion molecules in stem cell trafficking and homing.Curr Pharm Des.2011;17(30):3271-3279.
[19]Broxmeyer HE.Chemokines in hematopoiesis.Curr Opin Hematol.2008;15(1):49-58.
[20]Moll NM,Ransohoff RM.CXCL12 and CXCR4 in bone marrow physiology.Expert Rev Hematol.2010;3(3):315-322.
[21]Ghadge SK,Mühlstedt S,Ozcelik C,et al.SDF-1αas a therapeutic stem cell homing factor in myocardial infarction.Pharmacol Ther.2011;129(1):97-108.
[22]Wang Y,Deng Y,Zhou GQ.SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model.Brain Res.2008;1195:104-112.
[23]Shi M,Li J,Liao L,et al.Regulation of CXCR4expression in human mesenchymal stem cells by cytokine treatment:role in homing efficiency in NOD/SCID mice.Haematologica.2007;92(7):897-904.
[24]Tang JM,Wang JN,Zhang L,et al.VEGF/SDF-1promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart.Cardiovasc Res.2011;91(3):402-411.
[25]Bhakta S,Hong P,Koc O.The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation.Cardiovasc Revasc Med.2006;7(1):19-24.
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[27]Wang Y,Johnsen HE,Mortensen S,et al.Changes in circulating mesenchymal stem cells,stem cell homing factor,and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention.Heart.2006;92(6):768-774.
[28]Schenk S,Mal N,Finan A,et al.Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor.Stem Cells.2007;25(1):245-251.
[29]Huang J,Zhang Z,Guo J,et al.Genetic modification of mesenchymal stem cells overexpressing CCR1increases cell viability,migration,engraftment,and capillary density in the injured myocardium.Circ Res.2010;106(11):1753-1762.
[30]Guo J,Zhang H,Xiao J,et al.Monocyte chemotactic protein-1 promotes the myocardial homing of mesenchymal stem cells in dilated cardiomyopathy.Int J Mol Sci.2013;14(4):8164-8178.
[31]Que W,Chen J.Knockdown of c-Met inhibits cell proliferation and invasion and increases chemosensitivity to doxorubicin in human multiple myeloma U266 cells in vitro.Mol Med Rep.2011;4(2):343-349.
[32]Molnarfi N,Benkhoucha M,Funakoshi H,et al.Hepatocyte growth factor:A regulator of inflammation and autoimmunity.Autoimmun Rev.2015;14(4):293-303.
[33]Baek SJ,Kang SK,Ra JC.In vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors.Exp Mol Med.2011;43(10):596-603.
[34]Aenlle KK,Curtis KM,Roos BA,et al.Hepatocyte growth factor and p38 promote osteogenic differentiation of human mesenchymal stem cells.Mol Endocrinol.2014;28(5):722-730.
[35]Kucia M,Zhang YP,Reca R,et al.Cells enriched in markers of neural tissue-committed stem cells reside in the bone marrow and are mobilized into the peripheral blood following stroke.Leukemia.2006;20(1):18-28.
[36]Trapp T,K?gler G,El-Khattouti A,et al.Hepatocyte growth factor/c-MET axis-mediated tropism of cord blood-derived unrestricted somatic stem cells for neuronal injury.J Biol Chem.2008;283(47):32244-32253.
[37]黄小兵,李靖,梁平,等.龟板含药血清对骨髓间充质干细胞c-met表达及迁移的影响[J].中国中西医结合消化杂志,2013,21(11):569-571.
[38]Liu J,Pan G,Liang T,et al.HGF/c-Met signaling mediated mesenchymal stem cell-induced liver recovery in intestinal ischemia reperfusion model.Int J Med Sci.2014;11(6):626-633.
[39]Liu X,Shen W,Yang Y,et al.Therapeutic implications of mesenchymal stem cells transfected with hepatocyte growth factor transplanted in rat kidney with unilateral ureteral obstruction.J Pediatr Surg.2011;46(3):537-545.
[40]Brooke G,Tong H,Levesque JP,et al.Molecular trafficking mechanisms of multipotent mesenchymal stem cells derived from human bone marrow and placenta.Stem Cells Dev.2008;17(5):929-940.
[41]Steingen C,Brenig F,Baumgartner L,et al.Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells.J Mol Cell Cardiol.2008;44(6):1072-1084.
[42]Segers VF,Van Riet I,Andries LJ,et al.Mesenchymal stem cell adhesion to cardiac microvascular endothelium:activators and mechanisms.Am J Physiol Heart Circ Physiol.2006;290(4):H1370-1377.
[43]陆紫媛.TNF-α通过ERK/JNK-NF-κB信号通路刺激骨髓间充质干细胞表达VCAM-1[D].广州:南方医科大学,2014.
[44]吕浩敏,王爱玲,万俊.黏附分子在骨髓间充质干细胞的表达及向心肌梗死区归巢的作用[J].安徽医科大学学报,2012,47(4):415-418.
[45]Ip JE,Wu Y,Huang J,et al.Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor 4 for myocardial migration and engraftment.Mol Biol Cell.2007;18(8):2873-2882.
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