骨髓间充质干细胞的诱导分化机制及其在消化道组织再生中的作用
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摘要
骨髓间充质干细胞是一种具有多种分化潜能的非造血干细胞,它是从骨髓中分离得到,能被诱导分化为骨、软骨、肌肉、神经、血管内皮等多种类型的组织细胞,现已应用到再生医学的多个领域。本文将就骨髓间充质干细胞的诱导分化机制及其在促进消化道组织再生中的作用作一综述。
Bone marrow mesenchymal stem cell(BMSC) is the non-hematopoietic stem cell with good differentiating potential. BMSCs are mainly isolated from bone marrow. They can be differentiated into several types of cells like osteoblast, chondrocyte, muscle cell, neurons and endothelial cell etc. They have been studied in applications in vast areas of tissue regeneration. In this article, the differentiation mechanism of BMSC and how the BMSC promotes the regeneration of digestive system were reviewed.
Bone marrow mesenchymal stem cell(BMSC) is the non-hematopoietic stem cell with good differentiating potential. BMSCs are mainly isolated from bone marrow. They can be differentiated into several types of cells like osteoblast, chondrocyte, muscle cell, neurons and endothelial cell etc. They have been studied in applications in vast areas of tissue regeneration. In this article, the differentiation mechanism of BMSC and how the BMSC promotes the regeneration of digestive system were reviewed.
引文
[1]Shao J, Zhang W, Yang T. Using mesenchymal stem cells asatherapyforboneregenerationandrepairing.Biol Res, 2015, 48(1):62-68
[2]Friedenstein AJ,ChailakhjanRK,LalykinaKS.The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet, 1970, 3(4):393-403
[3]TongZ,Solanki A,Hamilos A,etal. Applicationof biomaterialstoadvanceinducedpluripotentstemcell research and therapy. EMBO J, 2015, 34(8):987-1008
[4]Wang M, Liang C, Hu H, et al. Intraperitoneal injection(IP),Intravenousinjection(IV)oranalinjection(AI)?Best way for mesenchymal stem cells transplantation for colitis. Sci Rep, 2016, 6:32-32
[5]Zhang GW, Gu TX, Guan XY, et al. bFGF binding cardiac extracellular matrix promotes the repair potential of bone marrow mesenchymal stem cells in a rabbit model foracutemyocardialinfarction.BiomedMater,2015,10(6):065018
[6]Xiong N, Yang H, Liu L, et al. bFGF promotes the differentiation and effectiveness of human bone marrow mesenchymal stem cells in a rotenone model for Parkinson's disease.Environ ToxicolPharmacol,2013,36(2):411-422
[7]Ramirez JJ, Finklestein SP, Keller J,et al. Basic fibroblast growthfactorenhancesaxonalsproutingaftercortical injury in rats. Neuroreport, 1999, 10(6):1201-1204
[8]ChenXQ,ChenLL,FanL,etal.Stemcellswith FGF4-bFGFfusedgeneenhancestheexpressionof bFGF and improves myocardial repair in rats. Biochem Biophys Res Commun, 2014, 447(1):145-151
[9]Ai G, Shao X, Meng M, et al. Epidermal growth factor promotesproliferationandmaintainsmultipotencyof continuousculturedadiposestemcellsviaactivating STAT signal pathway in vitro. Medicine, 2017, 96(30):e7607
[10]Chen J, Shen RD, Wang LN. EGF united HGF induced BMSCs differentiation into neuron-like cells. Jilin Med J,2013, 34(10):1805-1807
[11]Volz AC, Huber B, Schwandt AM, et al. EGF and hydrocortisone as critical factors for the co-culture of adipogenic differentiated ASCs and endothelial cells. Differentiation, 2017, 95:21-30
[12]Wang C, Li Y, Yang M, et al. Efficient differentiation of bonemarrowmesenchymalstemcellsintoendothelial cellsinvitro.EurJ VascEndovascSurg,2017,55(2):257-265
[13]Kang ML, Kim JE, Im GI. Vascular endothelial growth factor-transfected adipose-derived stromal cells enhance boneregenerationandneovascularizationfrombone marrowstromalcells.J TissueEngRegenMed,2017,11(12):3337-3348
[14]ZongX, WuS,LiF,etal. Transplantationof VEGFmediatedbonemarrowmesenchymalstemcellspromotesfunctionalimprovementinaratacutecerebral infarction model. Brain Res, 2017, 1676:9-18
[15]von Knoch F, Jaquiery C, Kowalsky M, et al. Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells. Biomaterials, 2005, 26(34):6941-6949
[16]Mohammad MH, Al-Shammari AM, Al-Juboory AA, et al.Characterizationofneuralstemnessstatusthrough the neurogenesis process for bone marrow mesenchymal stem cells. Stem Cells Cloning, 2016, 9:1-15
[17]PingJ,ChenHY,YangZ,etal.EffectofYiguan Decoction on differentiation of bone marrow mesenchymal stemcellsintohepatocyte-likecells:anexperimental research.ZhongguoZhongXi YiJieHeZaZhi,2014,34(3):348-354
[18]ZhangJF,LiG,ChanCY,etal.FlavonoidsofHerba Epimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt/beta-catenin signaling pathway. Mol Cell Endocrinol, 2010, 314(1):70-74
[19]Das RK, Gocheva V, Hammink R, et al. Stress-stiffeningmediated stem-cell commitment switch in soft responsive hydrogels. Nat Mater, 2015, 15(3):318-325
[20]Ovijit C, Koshy ST, Cristiana BDC, et al. Extracellular matrixstiffnessandcompositionjointlyregulatethe induction of malignant phenotypes in mammary epithelium.Nat Mater, 2014, 13(10):970-978
[21]WenJH, VincentLG,Fuhrmann A,etal.Interplayof Matrix Stiffness and Protein Tethering in Stem Cell Differentiation. Nat Mater, 2014, 13(10):979-987
[22]Sun M, Chi G, Li P, et al. Effects of matrix stiffness on the morphology, adhesion, proliferation and osteogenic differentiation of mesenchymal stem cells. Int J Med Sci,2018, 15(3):257-268
[23]Sun M, Chi G, Xu J, et al. Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin alpha5. Stem Cell Res Ther,2018, 9(1):52-64
[24]Jun-Ha H, Ran BM, A Rum K, et al. Extracellular matrix stiffnessregulatesosteogenicdifferentiationthrough MAPK activation. PLoS One, 2015, 10(8):e0135519
[25]Floren M, Bonani W, Dharmarajan A, et al. Human mesenchymal stem cells cultured on silk hydrogels with variable stiffness and growth factor differentiate into mature smooth muscle cell phenotype. Acta Biomater, 2016, 31:156-166
[26]Wingate K, Floren M, Tan Y, et al. Synergism of matrix stiffness and vascular endothelial growth factor on mesenchymalstemcellsforvascularendothelialregeneration. Tissue Eng Part A, 2014, 20(17-18):2503-2512
[27]Lee HJ, Diaz MF, Ewere A, et al. Focal adhesion kinase signalingregulatesanti-inflammatoryfunctionofbone marrowmesenchymalstromalcellsinducedbybiomechanical force. Cell Signal, 2017, 38:1-9
[28]HuK,SunH,GuiB,etal. TRPV4functionsinflow shearstressinducedearlyosteogenicdifferentiationof humanbonemarrowmesenchymalstemcells.Biomed Pharmacother, 2017, 91:841-848
[29]JunL,ZhiheZ,JuanL,etal.Hydrostaticpressures promoteinitialosteodifferentiationwithERK1/2not p38MAPKsignalinginvolved.JCellBiochem,2010,107(2):224-232
[30]Carroll SF, Buckley CT, Kelly DJ. Cyclic tensile strain canplayaroleindirectingbothintramembranousand endochondralossificationofmesenchymalstemcells.Front Bioeng Biotechnol, 2017, 5(2):73-84
[31]Sohda M and Kuwano H. Current status and future prospects for esophageal cancer treatment. Ann Thorac Cardiovasc Surg, 2017, 23(1):1-11
[32]Klevebro F, Ekman S and Nilsson M. Current trends in multimodality treatment of esophageal and gastroesophageal junction cancer-Review article. Surg Oncol, 2017,26(3):290-295
[33]OkamotoR, YajimaT, YamazakiM,etal.Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat Med, 2002, 8(9):1011-1017
[34]Kantarcioglu M, Caliskan B, Demirci H, et al. The efficacy of mesenchymal stem cell transplantation in caustic esophagus injury:an experimental study. Stem Cells Int,2014, 2014:1-7
[35]Tan B, Wei RQ, Tan MY, et al. Tissue engineered esophagus by mesenchymal stem cell seeding for esophageal repair in a canine model. J Surg Res, 2013, 182(1):40-48
[36]SjoqvistS,JungebluthP,LimML,etal.Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. Nat Commun, 2014, 5:3562-3576
[37]YabinZ,FattLM, WeyFengO,etal.Esophagealepithelium regeneration on fibronectin grafted poly(L-lactide-co-caprolactone)(PLLC)nanofiber scaffold. Biomaterials, 2007, 28(5):861-868
[38]Zhu Y, Chian KS, Chan-Park MB, et al. Protein bonding on biodegradable poly(L-lactide-co-caprolactone)membraneforesophagealtissueengineering.Biomaterials,2006, 27(1):68-78
[39]Zhu Y, Chan-Park MB. Density quantification of collagen graftedonbiodegradablepolyester:Itsapplicationto esophagealsmoothmusclecell. AnalBiochem,2007,363(1):119-127
[40]Zhu Y, Chan-Park MB and Sin CK. The growth improvement of porcine esophageal smooth muscle cells on collagen-grafted poly(DL-lactide-co-glycolide)membrane. J Biomed Mater Res B Appl Biomater, 2010, 75B(1):193-199
[41]Changfeng G, Lei H, Yabin Z, et al. In vitro constitution of esophageal muscle tissue with endocyclic and exolongitudinalpatterns. ACS ApplMaterInterfaces,2013,5(14):6549-6555
[42]Hou L, Jin J, Lv J, et al. Constitution and in vivo test of micro-porous tubular scaffold for esophageal tissue engineering. J Biomater Appl, 2015, 30(5):568-578
[43]Hou L, Gong C, Zhu Y. In vitro construction and in vivo regenerationofesophagealbilamellarmuscletissue.J Biomater Appl, 2016, 30(9):1373-1384
[44]Chang Q, Yan L, Wang CZ, et al. In vivo transplantation ofbonemarrowmesenchymalstemcellsaccelerates repairofinjuredgastricmucosainrats.ChinMedJ,2012, 125(6):1169-1174
[45]RashedL,GharibDM,HusseinRE,etal.Combined effect of bone marrow derived mesenchymal stem cells and nitric oxide inducer on injured gastric mucosa in a rat model. Tissue Cell, 2016, 48(6):644-652
[46]Gao R, Gao Z, Huang L, et al. Gut microbiota and colorectalcancer.EurJClinMicrobiolInfectDis,2017,36(5):757-769
[47]Ciccocioppo R, Cangemi GC, Kruzliak P, et al. Cellular therapies:The potential to regenerate and restore tolerance in immune-mediated intestinal diseases. Stem Cells,2016, 34(6):1474-1486
[48]ConklinLS,HanleyPJ,GalipeauJ,etal.Intravenous mesenchymalstromalcelltherapyforinflammatory bowel disease:lessons from the acute graft versus host disease experience. Cytotherapy, 2017, 19(6):655-667
[2]Friedenstein AJ,ChailakhjanRK,LalykinaKS.The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet, 1970, 3(4):393-403
[3]TongZ,Solanki A,Hamilos A,etal. Applicationof biomaterialstoadvanceinducedpluripotentstemcell research and therapy. EMBO J, 2015, 34(8):987-1008
[4]Wang M, Liang C, Hu H, et al. Intraperitoneal injection(IP),Intravenousinjection(IV)oranalinjection(AI)?Best way for mesenchymal stem cells transplantation for colitis. Sci Rep, 2016, 6:32-32
[5]Zhang GW, Gu TX, Guan XY, et al. bFGF binding cardiac extracellular matrix promotes the repair potential of bone marrow mesenchymal stem cells in a rabbit model foracutemyocardialinfarction.BiomedMater,2015,10(6):065018
[6]Xiong N, Yang H, Liu L, et al. bFGF promotes the differentiation and effectiveness of human bone marrow mesenchymal stem cells in a rotenone model for Parkinson's disease.Environ ToxicolPharmacol,2013,36(2):411-422
[7]Ramirez JJ, Finklestein SP, Keller J,et al. Basic fibroblast growthfactorenhancesaxonalsproutingaftercortical injury in rats. Neuroreport, 1999, 10(6):1201-1204
[8]ChenXQ,ChenLL,FanL,etal.Stemcellswith FGF4-bFGFfusedgeneenhancestheexpressionof bFGF and improves myocardial repair in rats. Biochem Biophys Res Commun, 2014, 447(1):145-151
[9]Ai G, Shao X, Meng M, et al. Epidermal growth factor promotesproliferationandmaintainsmultipotencyof continuousculturedadiposestemcellsviaactivating STAT signal pathway in vitro. Medicine, 2017, 96(30):e7607
[10]Chen J, Shen RD, Wang LN. EGF united HGF induced BMSCs differentiation into neuron-like cells. Jilin Med J,2013, 34(10):1805-1807
[11]Volz AC, Huber B, Schwandt AM, et al. EGF and hydrocortisone as critical factors for the co-culture of adipogenic differentiated ASCs and endothelial cells. Differentiation, 2017, 95:21-30
[12]Wang C, Li Y, Yang M, et al. Efficient differentiation of bonemarrowmesenchymalstemcellsintoendothelial cellsinvitro.EurJ VascEndovascSurg,2017,55(2):257-265
[13]Kang ML, Kim JE, Im GI. Vascular endothelial growth factor-transfected adipose-derived stromal cells enhance boneregenerationandneovascularizationfrombone marrowstromalcells.J TissueEngRegenMed,2017,11(12):3337-3348
[14]ZongX, WuS,LiF,etal. Transplantationof VEGFmediatedbonemarrowmesenchymalstemcellspromotesfunctionalimprovementinaratacutecerebral infarction model. Brain Res, 2017, 1676:9-18
[15]von Knoch F, Jaquiery C, Kowalsky M, et al. Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells. Biomaterials, 2005, 26(34):6941-6949
[16]Mohammad MH, Al-Shammari AM, Al-Juboory AA, et al.Characterizationofneuralstemnessstatusthrough the neurogenesis process for bone marrow mesenchymal stem cells. Stem Cells Cloning, 2016, 9:1-15
[17]PingJ,ChenHY,YangZ,etal.EffectofYiguan Decoction on differentiation of bone marrow mesenchymal stemcellsintohepatocyte-likecells:anexperimental research.ZhongguoZhongXi YiJieHeZaZhi,2014,34(3):348-354
[18]ZhangJF,LiG,ChanCY,etal.FlavonoidsofHerba Epimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt/beta-catenin signaling pathway. Mol Cell Endocrinol, 2010, 314(1):70-74
[19]Das RK, Gocheva V, Hammink R, et al. Stress-stiffeningmediated stem-cell commitment switch in soft responsive hydrogels. Nat Mater, 2015, 15(3):318-325
[20]Ovijit C, Koshy ST, Cristiana BDC, et al. Extracellular matrixstiffnessandcompositionjointlyregulatethe induction of malignant phenotypes in mammary epithelium.Nat Mater, 2014, 13(10):970-978
[21]WenJH, VincentLG,Fuhrmann A,etal.Interplayof Matrix Stiffness and Protein Tethering in Stem Cell Differentiation. Nat Mater, 2014, 13(10):979-987
[22]Sun M, Chi G, Li P, et al. Effects of matrix stiffness on the morphology, adhesion, proliferation and osteogenic differentiation of mesenchymal stem cells. Int J Med Sci,2018, 15(3):257-268
[23]Sun M, Chi G, Xu J, et al. Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin alpha5. Stem Cell Res Ther,2018, 9(1):52-64
[24]Jun-Ha H, Ran BM, A Rum K, et al. Extracellular matrix stiffnessregulatesosteogenicdifferentiationthrough MAPK activation. PLoS One, 2015, 10(8):e0135519
[25]Floren M, Bonani W, Dharmarajan A, et al. Human mesenchymal stem cells cultured on silk hydrogels with variable stiffness and growth factor differentiate into mature smooth muscle cell phenotype. Acta Biomater, 2016, 31:156-166
[26]Wingate K, Floren M, Tan Y, et al. Synergism of matrix stiffness and vascular endothelial growth factor on mesenchymalstemcellsforvascularendothelialregeneration. Tissue Eng Part A, 2014, 20(17-18):2503-2512
[27]Lee HJ, Diaz MF, Ewere A, et al. Focal adhesion kinase signalingregulatesanti-inflammatoryfunctionofbone marrowmesenchymalstromalcellsinducedbybiomechanical force. Cell Signal, 2017, 38:1-9
[28]HuK,SunH,GuiB,etal. TRPV4functionsinflow shearstressinducedearlyosteogenicdifferentiationof humanbonemarrowmesenchymalstemcells.Biomed Pharmacother, 2017, 91:841-848
[29]JunL,ZhiheZ,JuanL,etal.Hydrostaticpressures promoteinitialosteodifferentiationwithERK1/2not p38MAPKsignalinginvolved.JCellBiochem,2010,107(2):224-232
[30]Carroll SF, Buckley CT, Kelly DJ. Cyclic tensile strain canplayaroleindirectingbothintramembranousand endochondralossificationofmesenchymalstemcells.Front Bioeng Biotechnol, 2017, 5(2):73-84
[31]Sohda M and Kuwano H. Current status and future prospects for esophageal cancer treatment. Ann Thorac Cardiovasc Surg, 2017, 23(1):1-11
[32]Klevebro F, Ekman S and Nilsson M. Current trends in multimodality treatment of esophageal and gastroesophageal junction cancer-Review article. Surg Oncol, 2017,26(3):290-295
[33]OkamotoR, YajimaT, YamazakiM,etal.Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat Med, 2002, 8(9):1011-1017
[34]Kantarcioglu M, Caliskan B, Demirci H, et al. The efficacy of mesenchymal stem cell transplantation in caustic esophagus injury:an experimental study. Stem Cells Int,2014, 2014:1-7
[35]Tan B, Wei RQ, Tan MY, et al. Tissue engineered esophagus by mesenchymal stem cell seeding for esophageal repair in a canine model. J Surg Res, 2013, 182(1):40-48
[36]SjoqvistS,JungebluthP,LimML,etal.Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. Nat Commun, 2014, 5:3562-3576
[37]YabinZ,FattLM, WeyFengO,etal.Esophagealepithelium regeneration on fibronectin grafted poly(L-lactide-co-caprolactone)(PLLC)nanofiber scaffold. Biomaterials, 2007, 28(5):861-868
[38]Zhu Y, Chian KS, Chan-Park MB, et al. Protein bonding on biodegradable poly(L-lactide-co-caprolactone)membraneforesophagealtissueengineering.Biomaterials,2006, 27(1):68-78
[39]Zhu Y, Chan-Park MB. Density quantification of collagen graftedonbiodegradablepolyester:Itsapplicationto esophagealsmoothmusclecell. AnalBiochem,2007,363(1):119-127
[40]Zhu Y, Chan-Park MB and Sin CK. The growth improvement of porcine esophageal smooth muscle cells on collagen-grafted poly(DL-lactide-co-glycolide)membrane. J Biomed Mater Res B Appl Biomater, 2010, 75B(1):193-199
[41]Changfeng G, Lei H, Yabin Z, et al. In vitro constitution of esophageal muscle tissue with endocyclic and exolongitudinalpatterns. ACS ApplMaterInterfaces,2013,5(14):6549-6555
[42]Hou L, Jin J, Lv J, et al. Constitution and in vivo test of micro-porous tubular scaffold for esophageal tissue engineering. J Biomater Appl, 2015, 30(5):568-578
[43]Hou L, Gong C, Zhu Y. In vitro construction and in vivo regenerationofesophagealbilamellarmuscletissue.J Biomater Appl, 2016, 30(9):1373-1384
[44]Chang Q, Yan L, Wang CZ, et al. In vivo transplantation ofbonemarrowmesenchymalstemcellsaccelerates repairofinjuredgastricmucosainrats.ChinMedJ,2012, 125(6):1169-1174
[45]RashedL,GharibDM,HusseinRE,etal.Combined effect of bone marrow derived mesenchymal stem cells and nitric oxide inducer on injured gastric mucosa in a rat model. Tissue Cell, 2016, 48(6):644-652
[46]Gao R, Gao Z, Huang L, et al. Gut microbiota and colorectalcancer.EurJClinMicrobiolInfectDis,2017,36(5):757-769
[47]Ciccocioppo R, Cangemi GC, Kruzliak P, et al. Cellular therapies:The potential to regenerate and restore tolerance in immune-mediated intestinal diseases. Stem Cells,2016, 34(6):1474-1486
[48]ConklinLS,HanleyPJ,GalipeauJ,etal.Intravenous mesenchymalstromalcelltherapyforinflammatory bowel disease:lessons from the acute graft versus host disease experience. Cytotherapy, 2017, 19(6):655-667