干细胞在肌腱组织损伤修复中的潜能
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摘要
损伤的肌腱组织修复过程非常缓慢,并且很难恢复到原来结构完整和机械力学正常的状态。对肌腱基本特征的了解缺乏限制了挛缩肌腱治疗方法的发展。肌腱细胞再生能力有限,而外基质绝大多数由这种再生能力较弱的肌腱细胞分泌。肌腱损伤后即使在恢复应力后依靠自身的修复功能依然不可能逆转其挛缩的状态。因此,寻找新型的、可促进肌腱生理性再生修复的方法具有极其重要的临床意义,而发现合适的种子细胞和理想的诱导剂是组织工程化肌腱细胞构建的关键所在,其中一些方法包括利用胚胎干细胞、肌腱前体细胞、脂肪干细胞及相应的转录调控因子形成新的肌腱组织。
The repair process is very slow in tendon injuries. It is generally difficult to restore to its original structure of integrity and normal mechanical state. The lack of understanding in the basic features of the tendon contracture limits the development of tendon treatment. Because the tendon cells regeneration ability is very weak,and the vast majority of extracellular matrix is secreted by the tendon cells,it is almost impossible to reverse the contracture of the state on its own repair function after tendon recovery stress. Therefore,looking for new method promoting tendon physiological regenerative repair is of great clinical significance,and the key to the construction of tissue-engineered tendon cells is to find suitable seed cells and ideal inducers. Some of these methods are the use of embryonic stem cells,tendons precursor cells,adipose-derived stem cells and the corresponding transcription regulatory factors to form new tendon tissue.
The repair process is very slow in tendon injuries. It is generally difficult to restore to its original structure of integrity and normal mechanical state. The lack of understanding in the basic features of the tendon contracture limits the development of tendon treatment. Because the tendon cells regeneration ability is very weak,and the vast majority of extracellular matrix is secreted by the tendon cells,it is almost impossible to reverse the contracture of the state on its own repair function after tendon recovery stress. Therefore,looking for new method promoting tendon physiological regenerative repair is of great clinical significance,and the key to the construction of tissue-engineered tendon cells is to find suitable seed cells and ideal inducers. Some of these methods are the use of embryonic stem cells,tendons precursor cells,adipose-derived stem cells and the corresponding transcription regulatory factors to form new tendon tissue.
引文
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[3]刘运晃,邢更彦.肌腱细胞相关基础研究进展[J].实用医学杂志,2009,25(10):1715-1717.
[4]James HC Wang,Bhavani P Thampatty.成纤维细胞的力学生物学[J].中华骨科杂志,2007,27(6):477-480.
[5]Lee JY,Zhou Z,Taub PJ,et al.BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo[J].PLo S One,2011,6(3):e17531.
[6]Cao Y,Huo R,Feng Y,et al.Effects of intense pulsed light on the biological properties and ultrastructure of skin dermal fibroblasts:potential roles in photoaging[J].Photomed Laser Surg,2011,29(5):327-332.
[7]Chong AK,Chang J,Go JC.Mesenchymal stem cells and tendon healing[J].Front Biosci(Landmark Ed),2009,14:4598-4605.
[8]Via AG,Frizziero A,Oliva F.Biological properties of mesenchymal stem cells from different sources[J].Muscles Ligaments Tendons J,2012,2(3):154-162.
[9]Chen X,Yin Z,Ouyang HW,et al.Force and scleraxis synergistically promote the commitment of human ES cells derived MSCs to tenocytes[J].Sci Rep,2012,2:977.
[10]Luo Q,Song G,Song Y,et al.Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells[J].Cytotechnology,2009,61(1/2):1-10.
[11]Cai TY,Zhu W,Chen XS,et al.Fibroblast growth factor 2 induces mesenchymal stem cells to differentiate into tenocytes through the MAPK pathway[J].Mol Med Rep,2013,8(5):1323-1328.
[12]Ricchetti ET,Reddy SC,Beredjiklian PK,et al.Effect of interleukin-10 overexpression on the properties of healing tendon in a murine patellar tendon model[J].J Hand Surg Am,2008,33(10):1843-1852.
[13]Ruzehaji N,Kopecki Z,Cowin AJ,et al.Attenuation of flightless I improves wound healing and enhances angiogenesis in a murine model of type 1 diabetes[J].Diabetologia,2014,57(2):402-412.
[14]Chen X,Song XH,Yin Z,et al.Stepwise differentiation of human embryonic stem cells promotes tendon regeneration by secreting fetal tendon matrix and differentiation factors[J].Stem Cells,2009,27(6):1276-1287.
[15]Liu W,Yin L,Yan X,et al.Directing the differentiation of parthenogenetic stem cells into tenocytes for tissue-engineeredtendon regeneration[J].Stem Cells Transl Med,2017,6(1):196-208.
[16]张玉峰,程祥荣,施斌,等.诱导成体人牙周韧带干细胞向软骨细胞分化的实验研究[J].中华口腔医学杂志,2006,41(4):216-219.
[17]Bi Y,Ehirchiou D,Kilts TM,et al.Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche[J].Nat Med,2007,13(10):1219-1227.
[18]林禹丞,王宸,芮云峰,等.慢性腱病治疗的新策略:调控肌腱干细胞成肌腱分化促进肌腱愈合[J].中国矫形外科杂志,2013,21(21):2169-2176.
[19]Bi Y,Stuelten CH,Kilts T,et al.Extracellular matrix proteoglycans control the fate of bone marrow stromal cells[J].J Biol Chem,2005,280(34):30481-30489.
[20]Song F,Jiang D,Wang T,et al.Mechanical loading improves tendon-bone healing in a rabbit anterior cruciate ligament reconstruction model by promoting proliferation and matrix formation of mesenchymal stem cells and tendon cells[J].Cell Physiol Biochem,2017,41(3):875-889.
[21]Towler DA,Gelberman RH.The alchemy of tendon repair:a primer for the(S)mad scientist[J].J Clin Invest,2006,116(4):863-866.
[22]Zhang Y,Liu N,Tang Y,et al.Efficient generation of neural stem cell-like cells from rat adipose derived stem cells after lentiviral transduction with green fluorescent protein[J].Mol Neurobiol,2014,50(2):647-654.
[23]Deng D,Wang W,Wang B.Repair of achilles tendon defect with autologous ADSC engineered tendon in a rabbit model[J].Biomaterials,2014,35(31):8801-8809.
[24]Behfar M,Javanmardi S,Sarrafzadeh-Rezaei F.Comparative study on functional effects of allotransplantation of bone marrow stromal cells and adipose derived stromal vascular fraction on tendon repair:a biomechanical study in rabbits[J].Cell J,2014,16(3):263-270.
[25]Oh JH,Chung SW,Kim SH,et al.2013 Neer Award:Effect of the adipose-derived stem cell for the improvement of fatty degeneration and rotator cuff healing in rabbit model[J].J Shoulder Elbow Surg,2014,23(4):445-455.
[26]Chen HS,Su YT,Chan TM,et al.Human adipose-derived stem cells accelerate the restoration of tensile strength of tendon and alleviate the progression of rotator cuff injury in a rat model[J].Cell Transplant,2015,24(3):509-520.
[27]Yang G,Rothrauff BB,Lin H,et al.Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix[J].Biomaterials,2013,34(37):9295-9306.
[28]Schmitt T,Fox PM,Woon CY,et al.Human flexor tendon tissue engineering:in vivo effects of stem cell reseeding[J].Plast Reconstr Surg,2013,132(4):567e-576e.
[29]Hoffmann A,Pelled G,Turgeman G,et al.Neotendon formation induced by manipulation of the smad8 signalling pathway in mesenchymal stem cells[J].J Clin Invest,2006,116(4):940-952.
[30]Violini S,Ramelli P,Pisani LF,et al.Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12[J].BMC Cell Biol,2009,10:29.
[31]倪明,芮云峰,陈启明,等.生长分化因子7体外促进BMSCs向肌腱细胞分化的研究[J].中国修复重建外科杂志,2011,25(9):1103-1109.
[32]Wang QW,Chen ZL,Piao YJ.Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein(BMP)12 gene transfer[J].J Biosci Bioeng,2005,100(4):418-422.
[33]Uysal CA,Tobita M,Hyakusoku H,et al.Adipose-derived stem cells enhance primary tendon repair:biomechanical and immunohistochemical evaluation[J].J Plast Reconstr Aesthet Surg,2012,65(12):1712-1719.
[34]严明明,倪江东.脂肪干细胞在肌腱组织工程中的研究进展[J].中南大学学报(医学版),2014,39(2):199-203.
[35]Hee CK,Dines JS,Solchaga LA,et al.Regenerative ten-don and ligament healing:opportunities with recombinant human plateletderived growth factor BB-homodimer[J].Tissue Eng Part B Rev,2012,18(3):225-234.
[36]Xia C,Zuo J,Wang C,et al.Tendon healing in vivo:effect of mannose-6-phosphate on flexor tendon adhesion formation[J].Orthopedics,2012,35(7):e1056-1060.
[37]Okamoto S,Tohyama H,Kondo E,et al.Ex vivo supplementation of TGF-beta1 enhances the fibrous tissue re-generation effect of synovium-derived fibroblast transplantation in a tendon defect:a biomechanical study[J].Knee Surg Sports Traumatol Arthrosc,2008,16(3):333-339.
[38]朱红,曹文,李娅娟,等.磷酸果糖抑制肌腱胶原产生和趾屈指肌腱吻合后的粘连[J].中国组织工程研究,2013,17(8):1430-1434.
[39]聂继平,温树正,白志刚,等.去细胞异种肌腱复合IGF-I修复肌腱缺损的实验研究[J/CD].中华临床医师杂志(电子版),2013,7(17):7858-7863.
[40]姜月梅,邱轶伟,张鑫,等.胰岛素样生长因子-1和转化生长因子-β3对人肌腱细胞表型分化标志物mRNA表达的影响[J].中华实验外科杂志,2014,31(2):395-358.
[41]Sèdes L,Leclerc A,Moindjie H,et al.Anti-Müllerian hormone recruits BMPR-IA in immature granulosa cells[J].PLo S One,2013,8(11):e81551.
[42]MyllylRM,Haapasaari KM,Lehenkari P,et al.Bone morphogenetic proteins 4 and 2/7 induce osteogenic differentiation of mouse skin derived fibroblast and dermal papilla cells[J].Cell Tissue Res,2014,355(2):463-470.
[2]许锋,刘伟,曹谊林.肌腱细胞的生物学特性[J].中华医学研究杂志,2004,3(11):993-995.
[3]刘运晃,邢更彦.肌腱细胞相关基础研究进展[J].实用医学杂志,2009,25(10):1715-1717.
[4]James HC Wang,Bhavani P Thampatty.成纤维细胞的力学生物学[J].中华骨科杂志,2007,27(6):477-480.
[5]Lee JY,Zhou Z,Taub PJ,et al.BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo[J].PLo S One,2011,6(3):e17531.
[6]Cao Y,Huo R,Feng Y,et al.Effects of intense pulsed light on the biological properties and ultrastructure of skin dermal fibroblasts:potential roles in photoaging[J].Photomed Laser Surg,2011,29(5):327-332.
[7]Chong AK,Chang J,Go JC.Mesenchymal stem cells and tendon healing[J].Front Biosci(Landmark Ed),2009,14:4598-4605.
[8]Via AG,Frizziero A,Oliva F.Biological properties of mesenchymal stem cells from different sources[J].Muscles Ligaments Tendons J,2012,2(3):154-162.
[9]Chen X,Yin Z,Ouyang HW,et al.Force and scleraxis synergistically promote the commitment of human ES cells derived MSCs to tenocytes[J].Sci Rep,2012,2:977.
[10]Luo Q,Song G,Song Y,et al.Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells[J].Cytotechnology,2009,61(1/2):1-10.
[11]Cai TY,Zhu W,Chen XS,et al.Fibroblast growth factor 2 induces mesenchymal stem cells to differentiate into tenocytes through the MAPK pathway[J].Mol Med Rep,2013,8(5):1323-1328.
[12]Ricchetti ET,Reddy SC,Beredjiklian PK,et al.Effect of interleukin-10 overexpression on the properties of healing tendon in a murine patellar tendon model[J].J Hand Surg Am,2008,33(10):1843-1852.
[13]Ruzehaji N,Kopecki Z,Cowin AJ,et al.Attenuation of flightless I improves wound healing and enhances angiogenesis in a murine model of type 1 diabetes[J].Diabetologia,2014,57(2):402-412.
[14]Chen X,Song XH,Yin Z,et al.Stepwise differentiation of human embryonic stem cells promotes tendon regeneration by secreting fetal tendon matrix and differentiation factors[J].Stem Cells,2009,27(6):1276-1287.
[15]Liu W,Yin L,Yan X,et al.Directing the differentiation of parthenogenetic stem cells into tenocytes for tissue-engineeredtendon regeneration[J].Stem Cells Transl Med,2017,6(1):196-208.
[16]张玉峰,程祥荣,施斌,等.诱导成体人牙周韧带干细胞向软骨细胞分化的实验研究[J].中华口腔医学杂志,2006,41(4):216-219.
[17]Bi Y,Ehirchiou D,Kilts TM,et al.Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche[J].Nat Med,2007,13(10):1219-1227.
[18]林禹丞,王宸,芮云峰,等.慢性腱病治疗的新策略:调控肌腱干细胞成肌腱分化促进肌腱愈合[J].中国矫形外科杂志,2013,21(21):2169-2176.
[19]Bi Y,Stuelten CH,Kilts T,et al.Extracellular matrix proteoglycans control the fate of bone marrow stromal cells[J].J Biol Chem,2005,280(34):30481-30489.
[20]Song F,Jiang D,Wang T,et al.Mechanical loading improves tendon-bone healing in a rabbit anterior cruciate ligament reconstruction model by promoting proliferation and matrix formation of mesenchymal stem cells and tendon cells[J].Cell Physiol Biochem,2017,41(3):875-889.
[21]Towler DA,Gelberman RH.The alchemy of tendon repair:a primer for the(S)mad scientist[J].J Clin Invest,2006,116(4):863-866.
[22]Zhang Y,Liu N,Tang Y,et al.Efficient generation of neural stem cell-like cells from rat adipose derived stem cells after lentiviral transduction with green fluorescent protein[J].Mol Neurobiol,2014,50(2):647-654.
[23]Deng D,Wang W,Wang B.Repair of achilles tendon defect with autologous ADSC engineered tendon in a rabbit model[J].Biomaterials,2014,35(31):8801-8809.
[24]Behfar M,Javanmardi S,Sarrafzadeh-Rezaei F.Comparative study on functional effects of allotransplantation of bone marrow stromal cells and adipose derived stromal vascular fraction on tendon repair:a biomechanical study in rabbits[J].Cell J,2014,16(3):263-270.
[25]Oh JH,Chung SW,Kim SH,et al.2013 Neer Award:Effect of the adipose-derived stem cell for the improvement of fatty degeneration and rotator cuff healing in rabbit model[J].J Shoulder Elbow Surg,2014,23(4):445-455.
[26]Chen HS,Su YT,Chan TM,et al.Human adipose-derived stem cells accelerate the restoration of tensile strength of tendon and alleviate the progression of rotator cuff injury in a rat model[J].Cell Transplant,2015,24(3):509-520.
[27]Yang G,Rothrauff BB,Lin H,et al.Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix[J].Biomaterials,2013,34(37):9295-9306.
[28]Schmitt T,Fox PM,Woon CY,et al.Human flexor tendon tissue engineering:in vivo effects of stem cell reseeding[J].Plast Reconstr Surg,2013,132(4):567e-576e.
[29]Hoffmann A,Pelled G,Turgeman G,et al.Neotendon formation induced by manipulation of the smad8 signalling pathway in mesenchymal stem cells[J].J Clin Invest,2006,116(4):940-952.
[30]Violini S,Ramelli P,Pisani LF,et al.Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12[J].BMC Cell Biol,2009,10:29.
[31]倪明,芮云峰,陈启明,等.生长分化因子7体外促进BMSCs向肌腱细胞分化的研究[J].中国修复重建外科杂志,2011,25(9):1103-1109.
[32]Wang QW,Chen ZL,Piao YJ.Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein(BMP)12 gene transfer[J].J Biosci Bioeng,2005,100(4):418-422.
[33]Uysal CA,Tobita M,Hyakusoku H,et al.Adipose-derived stem cells enhance primary tendon repair:biomechanical and immunohistochemical evaluation[J].J Plast Reconstr Aesthet Surg,2012,65(12):1712-1719.
[34]严明明,倪江东.脂肪干细胞在肌腱组织工程中的研究进展[J].中南大学学报(医学版),2014,39(2):199-203.
[35]Hee CK,Dines JS,Solchaga LA,et al.Regenerative ten-don and ligament healing:opportunities with recombinant human plateletderived growth factor BB-homodimer[J].Tissue Eng Part B Rev,2012,18(3):225-234.
[36]Xia C,Zuo J,Wang C,et al.Tendon healing in vivo:effect of mannose-6-phosphate on flexor tendon adhesion formation[J].Orthopedics,2012,35(7):e1056-1060.
[37]Okamoto S,Tohyama H,Kondo E,et al.Ex vivo supplementation of TGF-beta1 enhances the fibrous tissue re-generation effect of synovium-derived fibroblast transplantation in a tendon defect:a biomechanical study[J].Knee Surg Sports Traumatol Arthrosc,2008,16(3):333-339.
[38]朱红,曹文,李娅娟,等.磷酸果糖抑制肌腱胶原产生和趾屈指肌腱吻合后的粘连[J].中国组织工程研究,2013,17(8):1430-1434.
[39]聂继平,温树正,白志刚,等.去细胞异种肌腱复合IGF-I修复肌腱缺损的实验研究[J/CD].中华临床医师杂志(电子版),2013,7(17):7858-7863.
[40]姜月梅,邱轶伟,张鑫,等.胰岛素样生长因子-1和转化生长因子-β3对人肌腱细胞表型分化标志物mRNA表达的影响[J].中华实验外科杂志,2014,31(2):395-358.
[41]Sèdes L,Leclerc A,Moindjie H,et al.Anti-Müllerian hormone recruits BMPR-IA in immature granulosa cells[J].PLo S One,2013,8(11):e81551.
[42]MyllylRM,Haapasaari KM,Lehenkari P,et al.Bone morphogenetic proteins 4 and 2/7 induce osteogenic differentiation of mouse skin derived fibroblast and dermal papilla cells[J].Cell Tissue Res,2014,355(2):463-470.