调控骨髓间充质干细胞成软骨分化的研究进展
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摘要
成体骨髓间充质干细胞(BMSCs)具有多向分化的能力,是软骨组织工程常用的种子细胞。诱导BMSCs成软骨分化对于体外或体内构建组织工程化软骨都具有重要意义,而目前已有多种促进BMSCs成软骨分化的诱导方式,却依然没有一个最优化的方法可以获得既保存良好增殖能力、不发生细胞肥大,又能分化成软骨具备透明软骨表型。本文对目前的大部分使BMSCs成软骨分化的方法做一综述,希望能为开发最优诱导分化方案提供参考。
The adult bone mesenchymal stem cells(BMSCs) are commonly used as seed cells in cartilage tissue engineering which have the multi-differenciation potentials. Inducing the chondrogenesis of BMSCs is a vital part of tissue-engineered cartilage construction, yet till now many methods for chondrogenesis induction can not fulfill the demands of chondrocyte differentiation without hypertrophy. The purpose of this review was to summarize the different induction methods, thus provide reference for developing optimized programs for chondrogenesis of BMSCs.
The adult bone mesenchymal stem cells(BMSCs) are commonly used as seed cells in cartilage tissue engineering which have the multi-differenciation potentials. Inducing the chondrogenesis of BMSCs is a vital part of tissue-engineered cartilage construction, yet till now many methods for chondrogenesis induction can not fulfill the demands of chondrocyte differentiation without hypertrophy. The purpose of this review was to summarize the different induction methods, thus provide reference for developing optimized programs for chondrogenesis of BMSCs.
引文
[1]冯均伟,王跃,吕波,等.骨髓间充质干细胞体外诱导成软骨细胞的动态观察[J].中国组织工程研究,2013,17(36):6409-6416.
[2]刘天一,周广东,魏娴,等.转化生长因子β1诱导时间对骨髓基质细胞体外成软骨分化的影响[J].中华医学杂志,2007,87(31):2218-2222.
[3]邓进,彭吾训,王蕾,等.骨髓间充质干细胞二维培养条件下向软骨细胞诱导分化的实验研究[J].中国现代医学杂志,2008,18(16):2340-2343.
[4]方军,李华壮,高克海,等.体外团状培养系统中Ad-h TGF-β1诱导骨髓间充质干细胞向软骨细胞的分化[J].中国组织工程研究与临床康复,2009,13(49):9717-9721.
[5]鞠晓东,敖英芳,王建全,等.腺病毒介导人转化生长因子β2基因转染诱导骨髓间充质干细胞向软骨细胞的定向分化[J].中国组织工程研究与临床康复,2010,14(49):9194-9198.
[6]Arikawa T,Matsukawa A,Watanabe K,et al.Galectin-9accelerates transforming growth factor beta 3-induced differentiation of human mesenchymal stem cells to chondrocytes[J].Bone,2009,44(5):849-857.
[7]Longobardi L,O’Rear L,Aakula S,et al.Effect of IGF-1 in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling[J].J Bone Minera Res,2006,21(4):626-636.
[8]汪健,李小飞,田苗,等.骨形态发生蛋白对兔骨髓间充质干细胞成软骨分化的定向诱导作用[J].中华实验外科杂志,2005,22(7):829-831.
[9]Zhou N,Hu N,Liao JY,et al.HIF-1 alpha as a Regulator of BMP2-Induced Chondrogenic Differentiation,Osteogenic Differentiation,and Endochondral Ossification in Stem Cells[J].Cell Physiol Biochem,2015,36(1):44-60.
[10]Mwale F,Yao GY,Ouellet JA,et al.Effect of parathyroid hormone on type X and type II collagen expression in mesenchymal stem cells from osteoarthritic patients[J].Tissue Eng Part A,2010,16(11):3449-3455.
[11]Zhang Y,Kumagai K,Saito T.Effect of parathyroid hormone on early chondrogenic differentiation from mesenchymal stem cells[J].J Orthop Surg Res,2014,9:68.
[12]Mueller MB,Fischer M,Zellner J,et al.Effect of parathyroid hormone-related protein in an in vitro hypertrophy model for mesenchymal stem cell chondrogenesis[J].Int Orthop,2013,37(5):945-951.
[13]Kim YJ,Kim HJ,Im GI.PTHr P promotes chondrogenesis and suppresses hypertrophy from both bone marrow-derived and adipose tissue-derived MSCs[J].Biochem Biophys Res Commun,2008,373(1):104–108.
[14]Lee JM,Im GI.PTHr P isoforms have differing effect on chondrogenic differentiation and hypertrophy of mesenchymal stem cells[J].Biochem Biophys Res Commun,2012,421(4):819-824.
[15]Chen Y,Chen Y,Zhang S,et al.Parathyroid Hormone-Induced Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and its Repair of Articular Cartilage Injury in Rabbits[J].Med Sci Monit Basic Res,2016;22:132–145.
[16]Fischer J,Aulmann A,Dexheimer V,et al.Intermittent PTHr P(1-34)exposure augments chondrogenesis and reduces hypertrophy of mesenchymal stromal cells[J].Stem Cells Dev,2014,23(20):2513-2523.
[17]Liu Y,He L,Tian J,et al.Effect of basic fibroblast growth factor and parathyroid hormone-related protein on early and late chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells induced by transforming growth factor beta 1[J].Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi,2013,27(2):199-206.
[18]Weiss S,Hennig T,Bock R,et al.Impact of growth factors and PTHr P on early and late chondrogenic differentiation of human mesenchymal stem cells[J].J Cell Physiol,2010,223(1):84-93.
[19]晏杰,刘玲蓉,张其清.诱导骨髓间充质干细胞向软骨细胞分化的体外研究[J].中国修复重建外科杂志,2006,20(11):1114-1118.
[20]张清林,吕惠成,吴一民.转化生长因子β1联合骨形态发生蛋白2诱导骨髓间充质干细胞体外向软骨细胞的分化[J].中国组织工程研究与临床康复,2010,14(24):4371-4375.
[21]张云鹏,白希壮,孙羽.BMP-14与b FGF联合诱导骨髓间充质干细胞向软骨分化的实验研究[J].中国医科大学学报,2009,38(12):898-899,903.
[22]Worster AA,Brower-Toland BD,Fortier LA,et al.Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-p1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix[J].J Orthop Res,2001,19(4):738-749.
[23]Tian Y,Guo R,Shi B,et al.MicroRNA-30a promotes chondrogenic differentiation of mesenchymal stem cells through inhibiting Delta-like 4 expression[J].Life Sci,2016,148:220-228.
[24]苏金梅,金晔,曲强,等.骨髓间充质干细胞向软骨细胞分化过程中miR130a的表达[J].基础医学与临床,2010,30(5):520-523.
[25]Ham O,Song BW,Lee SY,et al.The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling[J].Biomaterials,2012,33(18):4500-4507.
[26]王万宗,陈宗雄,刘晓强.骨髓间充质干细胞与关节软骨细胞Transwell共培养诱导形成软骨[J].中国组织工程研究与临床康复,2010,14(38):7041-7044.
[27]张瑾,张子琦,张滟,等.微囊化软骨细胞诱导骨髓间充质干细胞的体外定向分化[J].中国组织工程研究,2014,18(30):4790-4796.
[28]苗春雷,周广东,刘天一,等.软骨细胞与骨髓基质细胞共培养体外构建软骨的初步研究[J].上海第二医科大学学报,2004,24(4):246-249,283.
[29]Aung A,Gupta G,Majid G,et al.Osteoarthritic ChondrocyteSecreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells[J].Arthritis Rheum,2011,63(1):148-158.
[30]Fischer J,Dickhut A,Rickert M,et al.Human articular chondrocytes secrete parathyroid hormone–related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis[J].Arthritis Rheum,2010,62(9):2696–2706.
[31]Bosnakovski D,Mizuno M,Kim G,et al.Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells(MSCs)in different hydrogels:influence of collagen type II extracellular matrix on MSC chondrogenesis[J].Biotechnol Bioeng.2006,93(6):1152-1163.
[32]N9th U,Rackwitz L,Heymer A,et al.Chondrogenic differentiation of human mesenchymal stem cells in collagen type I hydrogels[J].J Biomed Mater Res A,2007,83(3):626-635.
[33]寇建强,王昌耀,王英振.外源性透明质酸对兔骨髓间充质干细胞定向分化为软骨细胞的影响[J].中国组织工程研究与临床康复,2011,15(3):381-385.
[34]Karunanithi P,Murali MR,Samuel S,et al.Three dimensional alginate-fucoidan composite hydrogel augments the chondrogenic differentiation of mesenchymal stromal cells[J].Carbohydr Polym,2016,147:294-303.
[35]Choi JW,Choi BH,Park SH,et al.Mechanical stimulation by ultrasound enhances chondrogenic differentiation of mesenchymal stem cells in a Fibrin-Hyaluronic acid hydrogel[J].Artif Organs,2013,37(7):648-655.
[36]Lim SM,Oh SH,Lee HH,et al.Dual growth factor-releasing nanoparticle/hydrogel system for cartilage tissue engineering[J].J Mater Sci Mater Med,2010,21(9):2593-2600.
[37]Jae WL,Hyoseok A,Kuen YL,et al.Introduction of N-cadherinbinding motif to alginate hydrogels for controlled stem cell differentiation[J].Colloids Surf B Biointerfaces,2017,155:229-237.
[38]Yao Y,Huang Y,Qian D,et al.Effect of various ratios of cocultured ATDC5 cells and chondrocytes ontheexpression of cartilaginous phenotype in microcavitary alginate hydrogel[J].J Cell Biochem,2017,118(11):3607-3615.
[39]戴云,何静,吴方.基底膜基质/壳聚糖诱导骨髓间充质干细胞成软骨分化[J].中国组织工程研究,2015,19(10):1506-1510.
[40]Spadaccio C,Rainer A.Poly-L-Lactic acid/hydroxyapatite electrospun nanocomposites induce chondrogenic differentiation of human MSC[J].Ann Biomed Eng,2009,37(7):1376–1389.
[41]苗春雷,牟少春,梁晓琴,等.软骨细胞与骨髓基质细胞共培养裸鼠体内构建软骨组织的实验研究[J].中国美容医学,2010,19(2):204-207.
[42]吴广文,刘伯龄,刘献样,等.疏密波最佳波段组合诱导大鼠骨髓问充质十细胞向软骨细胞的分化[J].中国组织工程研究与临床康复,2009,13(6):1059-1063.
[43]Zscharnack M,Poesel C,Galle J,et al.Low Oxygen expansion improves subsequent chondrogenesis of ovine Bone-Marrow-Derived mesenchymal stem cells in collagen type I hydrogel[J].Cells Tissues Organs,2009,190(2):81-93.
[44]Meretoja VV,Dahlin RL,Wright S,et al.The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds[J].Biomaterials,2013,34(17):4266-4273.
[45]Takagi M,Umetsu Y,Fujiwara M,et al.High inoculation cell density could accelerate the differentiation of human bone marrow mesenchymal stem cells to chondrocyte cells[J].J Biosci Bioeng,2007,103(1):98-100.
[46]Guo T,Yu L,Lim CG,et al.Effect of dynamic culture and periodic compression on human mesenchymal stem cell proliferation and chondrogenesis[J].Ann Biomed Eng,2016,44(7):2103-2113.
[2]刘天一,周广东,魏娴,等.转化生长因子β1诱导时间对骨髓基质细胞体外成软骨分化的影响[J].中华医学杂志,2007,87(31):2218-2222.
[3]邓进,彭吾训,王蕾,等.骨髓间充质干细胞二维培养条件下向软骨细胞诱导分化的实验研究[J].中国现代医学杂志,2008,18(16):2340-2343.
[4]方军,李华壮,高克海,等.体外团状培养系统中Ad-h TGF-β1诱导骨髓间充质干细胞向软骨细胞的分化[J].中国组织工程研究与临床康复,2009,13(49):9717-9721.
[5]鞠晓东,敖英芳,王建全,等.腺病毒介导人转化生长因子β2基因转染诱导骨髓间充质干细胞向软骨细胞的定向分化[J].中国组织工程研究与临床康复,2010,14(49):9194-9198.
[6]Arikawa T,Matsukawa A,Watanabe K,et al.Galectin-9accelerates transforming growth factor beta 3-induced differentiation of human mesenchymal stem cells to chondrocytes[J].Bone,2009,44(5):849-857.
[7]Longobardi L,O’Rear L,Aakula S,et al.Effect of IGF-1 in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling[J].J Bone Minera Res,2006,21(4):626-636.
[8]汪健,李小飞,田苗,等.骨形态发生蛋白对兔骨髓间充质干细胞成软骨分化的定向诱导作用[J].中华实验外科杂志,2005,22(7):829-831.
[9]Zhou N,Hu N,Liao JY,et al.HIF-1 alpha as a Regulator of BMP2-Induced Chondrogenic Differentiation,Osteogenic Differentiation,and Endochondral Ossification in Stem Cells[J].Cell Physiol Biochem,2015,36(1):44-60.
[10]Mwale F,Yao GY,Ouellet JA,et al.Effect of parathyroid hormone on type X and type II collagen expression in mesenchymal stem cells from osteoarthritic patients[J].Tissue Eng Part A,2010,16(11):3449-3455.
[11]Zhang Y,Kumagai K,Saito T.Effect of parathyroid hormone on early chondrogenic differentiation from mesenchymal stem cells[J].J Orthop Surg Res,2014,9:68.
[12]Mueller MB,Fischer M,Zellner J,et al.Effect of parathyroid hormone-related protein in an in vitro hypertrophy model for mesenchymal stem cell chondrogenesis[J].Int Orthop,2013,37(5):945-951.
[13]Kim YJ,Kim HJ,Im GI.PTHr P promotes chondrogenesis and suppresses hypertrophy from both bone marrow-derived and adipose tissue-derived MSCs[J].Biochem Biophys Res Commun,2008,373(1):104–108.
[14]Lee JM,Im GI.PTHr P isoforms have differing effect on chondrogenic differentiation and hypertrophy of mesenchymal stem cells[J].Biochem Biophys Res Commun,2012,421(4):819-824.
[15]Chen Y,Chen Y,Zhang S,et al.Parathyroid Hormone-Induced Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and its Repair of Articular Cartilage Injury in Rabbits[J].Med Sci Monit Basic Res,2016;22:132–145.
[16]Fischer J,Aulmann A,Dexheimer V,et al.Intermittent PTHr P(1-34)exposure augments chondrogenesis and reduces hypertrophy of mesenchymal stromal cells[J].Stem Cells Dev,2014,23(20):2513-2523.
[17]Liu Y,He L,Tian J,et al.Effect of basic fibroblast growth factor and parathyroid hormone-related protein on early and late chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells induced by transforming growth factor beta 1[J].Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi,2013,27(2):199-206.
[18]Weiss S,Hennig T,Bock R,et al.Impact of growth factors and PTHr P on early and late chondrogenic differentiation of human mesenchymal stem cells[J].J Cell Physiol,2010,223(1):84-93.
[19]晏杰,刘玲蓉,张其清.诱导骨髓间充质干细胞向软骨细胞分化的体外研究[J].中国修复重建外科杂志,2006,20(11):1114-1118.
[20]张清林,吕惠成,吴一民.转化生长因子β1联合骨形态发生蛋白2诱导骨髓间充质干细胞体外向软骨细胞的分化[J].中国组织工程研究与临床康复,2010,14(24):4371-4375.
[21]张云鹏,白希壮,孙羽.BMP-14与b FGF联合诱导骨髓间充质干细胞向软骨分化的实验研究[J].中国医科大学学报,2009,38(12):898-899,903.
[22]Worster AA,Brower-Toland BD,Fortier LA,et al.Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-p1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix[J].J Orthop Res,2001,19(4):738-749.
[23]Tian Y,Guo R,Shi B,et al.MicroRNA-30a promotes chondrogenic differentiation of mesenchymal stem cells through inhibiting Delta-like 4 expression[J].Life Sci,2016,148:220-228.
[24]苏金梅,金晔,曲强,等.骨髓间充质干细胞向软骨细胞分化过程中miR130a的表达[J].基础医学与临床,2010,30(5):520-523.
[25]Ham O,Song BW,Lee SY,et al.The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling[J].Biomaterials,2012,33(18):4500-4507.
[26]王万宗,陈宗雄,刘晓强.骨髓间充质干细胞与关节软骨细胞Transwell共培养诱导形成软骨[J].中国组织工程研究与临床康复,2010,14(38):7041-7044.
[27]张瑾,张子琦,张滟,等.微囊化软骨细胞诱导骨髓间充质干细胞的体外定向分化[J].中国组织工程研究,2014,18(30):4790-4796.
[28]苗春雷,周广东,刘天一,等.软骨细胞与骨髓基质细胞共培养体外构建软骨的初步研究[J].上海第二医科大学学报,2004,24(4):246-249,283.
[29]Aung A,Gupta G,Majid G,et al.Osteoarthritic ChondrocyteSecreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells[J].Arthritis Rheum,2011,63(1):148-158.
[30]Fischer J,Dickhut A,Rickert M,et al.Human articular chondrocytes secrete parathyroid hormone–related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis[J].Arthritis Rheum,2010,62(9):2696–2706.
[31]Bosnakovski D,Mizuno M,Kim G,et al.Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells(MSCs)in different hydrogels:influence of collagen type II extracellular matrix on MSC chondrogenesis[J].Biotechnol Bioeng.2006,93(6):1152-1163.
[32]N9th U,Rackwitz L,Heymer A,et al.Chondrogenic differentiation of human mesenchymal stem cells in collagen type I hydrogels[J].J Biomed Mater Res A,2007,83(3):626-635.
[33]寇建强,王昌耀,王英振.外源性透明质酸对兔骨髓间充质干细胞定向分化为软骨细胞的影响[J].中国组织工程研究与临床康复,2011,15(3):381-385.
[34]Karunanithi P,Murali MR,Samuel S,et al.Three dimensional alginate-fucoidan composite hydrogel augments the chondrogenic differentiation of mesenchymal stromal cells[J].Carbohydr Polym,2016,147:294-303.
[35]Choi JW,Choi BH,Park SH,et al.Mechanical stimulation by ultrasound enhances chondrogenic differentiation of mesenchymal stem cells in a Fibrin-Hyaluronic acid hydrogel[J].Artif Organs,2013,37(7):648-655.
[36]Lim SM,Oh SH,Lee HH,et al.Dual growth factor-releasing nanoparticle/hydrogel system for cartilage tissue engineering[J].J Mater Sci Mater Med,2010,21(9):2593-2600.
[37]Jae WL,Hyoseok A,Kuen YL,et al.Introduction of N-cadherinbinding motif to alginate hydrogels for controlled stem cell differentiation[J].Colloids Surf B Biointerfaces,2017,155:229-237.
[38]Yao Y,Huang Y,Qian D,et al.Effect of various ratios of cocultured ATDC5 cells and chondrocytes ontheexpression of cartilaginous phenotype in microcavitary alginate hydrogel[J].J Cell Biochem,2017,118(11):3607-3615.
[39]戴云,何静,吴方.基底膜基质/壳聚糖诱导骨髓间充质干细胞成软骨分化[J].中国组织工程研究,2015,19(10):1506-1510.
[40]Spadaccio C,Rainer A.Poly-L-Lactic acid/hydroxyapatite electrospun nanocomposites induce chondrogenic differentiation of human MSC[J].Ann Biomed Eng,2009,37(7):1376–1389.
[41]苗春雷,牟少春,梁晓琴,等.软骨细胞与骨髓基质细胞共培养裸鼠体内构建软骨组织的实验研究[J].中国美容医学,2010,19(2):204-207.
[42]吴广文,刘伯龄,刘献样,等.疏密波最佳波段组合诱导大鼠骨髓问充质十细胞向软骨细胞的分化[J].中国组织工程研究与临床康复,2009,13(6):1059-1063.
[43]Zscharnack M,Poesel C,Galle J,et al.Low Oxygen expansion improves subsequent chondrogenesis of ovine Bone-Marrow-Derived mesenchymal stem cells in collagen type I hydrogel[J].Cells Tissues Organs,2009,190(2):81-93.
[44]Meretoja VV,Dahlin RL,Wright S,et al.The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds[J].Biomaterials,2013,34(17):4266-4273.
[45]Takagi M,Umetsu Y,Fujiwara M,et al.High inoculation cell density could accelerate the differentiation of human bone marrow mesenchymal stem cells to chondrocyte cells[J].J Biosci Bioeng,2007,103(1):98-100.
[46]Guo T,Yu L,Lim CG,et al.Effect of dynamic culture and periodic compression on human mesenchymal stem cell proliferation and chondrogenesis[J].Ann Biomed Eng,2016,44(7):2103-2113.