干细胞组织工程技术辅助下颌牵张成骨的研究与进展
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摘要
背景:下颌牵张成骨在临床取得重大反响以来,大量学者致力于增强成骨、缩短疗程的研究,其中干细胞移植作为当前的热点备受关注。目的:总结目前使用干细胞组织工程技术辅助下颌牵张成骨的进展与不足。方法:遵循PRISMA指南,由第一作者以"牵张成骨,下颌骨,下颌,干细胞"为中文检索词,以"distraction osteogenesis,mandibular,mandible,stemcells"为英文检索词,对PubMed、WOS、CNKI、万方等数据库分别进行检索,对文献中的动物模型、干细胞种类及移植方式等进行统计并制表做简要介绍。结果与结论:从目标文献中严格按照标准筛选出51篇文献进行分析、总结。文献中干细胞移植的时机、方式及种类等有着很大的差异。大量动物实验结果证实干细胞组织工程技术可以增强下颌牵张成骨中骨与血管的再生。探讨干细胞组织工程技术辅助下颌牵张成骨中干细胞的选择与应用,不仅能为将来的治疗提供思路,还能为接下来的临床试验打下基础。
BACKGROUND: Since mandibular distraction osteogenesis has achieved significant repercussions in clinical practice, many scholars have been working on studies that enhancing osteogenesis and shortening the course of treatment. Among them, stem cell transplantation has attracted much attention as a hotspot.OBJECTIVE: To summarize the current progress and deficiency of stem cell-based tissue engineering technology assisting mandibular distraction osteogenesis.METHODS: Following the PRISMA guidelines, a computer-based search of PubMed, WOS, CNKI and WanFang databases was performed by the first author for relevant articles with the keywords of "distraction osteogenesis,mandibular, mandible, stem cells" in English and Chinese, respectively. Animal models, types of stem cells and routes of transplantation in the selected literature were extracted and counted up. The results were tabulated and introduced briefly.RESULTS AND CONCLUSION: Fifty-one articles were strictly selected as per the eligibility criteria, analyzed and summarized. In the selected literature, the timing, methods and types of stem cell transplantation vary greatly. The majority of animal experimental studies have confirmed that stem cell-based tissue engineering technology can enhance bone and blood vessel regeneration in mandibular distraction osteogenesis. Explorations on the selection and application of stem cells in mandibular distraction osteogenesis assisted by stem cell-based tissue engineering technology cannot only provide ideas for future treatment, but also lay the foundation for clinical trials.
BACKGROUND: Since mandibular distraction osteogenesis has achieved significant repercussions in clinical practice, many scholars have been working on studies that enhancing osteogenesis and shortening the course of treatment. Among them, stem cell transplantation has attracted much attention as a hotspot.OBJECTIVE: To summarize the current progress and deficiency of stem cell-based tissue engineering technology assisting mandibular distraction osteogenesis.METHODS: Following the PRISMA guidelines, a computer-based search of PubMed, WOS, CNKI and WanFang databases was performed by the first author for relevant articles with the keywords of "distraction osteogenesis,mandibular, mandible, stem cells" in English and Chinese, respectively. Animal models, types of stem cells and routes of transplantation in the selected literature were extracted and counted up. The results were tabulated and introduced briefly.RESULTS AND CONCLUSION: Fifty-one articles were strictly selected as per the eligibility criteria, analyzed and summarized. In the selected literature, the timing, methods and types of stem cell transplantation vary greatly. The majority of animal experimental studies have confirmed that stem cell-based tissue engineering technology can enhance bone and blood vessel regeneration in mandibular distraction osteogenesis. Explorations on the selection and application of stem cells in mandibular distraction osteogenesis assisted by stem cell-based tissue engineering technology cannot only provide ideas for future treatment, but also lay the foundation for clinical trials.
引文
[1]Primrose AC,Broadfoot E,Diner PA,et al.Patients'responses to distraction osteogenesis:a multi-centre study.Int J Oral Maxillofac Surg.2005;34(3):238-242.
[2]王良,李军,沈毅,等.虚拟手术辅助的血管化腓骨肌(皮)瓣行下颌骨精确重建[J].中国耳鼻咽喉颅底外科杂志,2016,22(3):220-224.
[3]张赛,张龙城.下颌骨缺损修复的研究进展[J].中国耳鼻咽喉颅底外科杂志,2017,23(2):177-181.
[4]邹霓.骨组织工程人工合成支架材料的研究现状[J].中国组织工程研究与临床康复,2008,12(23):4481-4484.
[5]Codivilla A.The classic:On the means of lengthening,in the lower limbs,the muscles and tissues which are shortened through deformity.1905.Clin Orthop Relat Res.2008;466(12):2903-2909.
[6]Ilizarov GA.The principles of the Ilizarov method.1988.Bull Hosp Jt Dis.1997;56(1):49-53.
[7]McCarthy JG,Schreiber J,Karp N,et al.Lengthening the human mandible by gradual distraction.Plast Reconstr Surg.1992;89(1):1-8;discussion 9-10.
[8]N?rholt SE,Jensen J,Schou S,et al.Complications after mandibular distraction osteogenesis:a retrospective study of 131patients.Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2011;111(4):420-427.
[9]Ai-Aql ZS,Alagl AS,Graves DT,et al.Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis.J Dent Res.2008;87(2):107-118.
[10]Khedr MS,Abdel Al SE,Osman MM,et al.The effect of electrical stimulation on mandibular distraction osteogenesis.Egyptian Journal of Oral&Maxillofacial Surgery.2011;2(2):41-49.
[11]Xie LK,Wangrangsimakul K,Suttapreyasri S,et al.A preliminary study of the effect of low intensity pulsed ultrasound on new bone formation during mandibular distraction osteogenesis in rabbits.Int J Oral Maxillofac Surg.2011;40(7):730-736.
[12]Wang L,Zhou S,Liu B,et al.Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis.J Orthop Res.2006;24(12):2238-2245.
[13]Ma G,Zhao JL,Mao M,et al.Scaffold-Based Delivery of Bone Marrow Mesenchymal Stem Cell Sheet Fragments Enhances New Bone Formation In Vivo.J Oral Maxillofac Surg.2017;75(1):92-104.
[14]El Hadidi YN,El Kassaby M,El Fatah Ahmed SA,et al.Effect of Mesenchymal Stem Cell Application on the Distracted Bone Microstructure:An Experimental Study.J Oral Maxillofac Surg.2016;74(7):1463.e1-1463.e11.
[15]Zheutlin AR,Deshpande SS,Nelson NS,et al.Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis:A histomorphometric evaluation.Cytotherapy.2016;18(5):664-672.
[16]Zeng JJ,Guo P,Zhou N,et al.Treatment of large bone defects with a novel biological transport disc in non-vascular transport distraction osteogenesis.Int J Oral Maxillofac Surg.2016;45(5):670-677.
[17]冯桂娟,郑科,宋冬惠,等.Runt相关基因2修饰的骨髓间充质干细胞促进兔下颌骨牵张成骨的研究[J].华西口腔医学杂志,2016,34(2):125-129.
[18]Deshpande SS,Gallagher KK,Donneys A,et al.Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.Plast Reconstr Surg.2015;135(3):799-806.
[19]王亚茜.EPCs在犬下颌骨非血管化输送盘牵张成骨血管新生中的作用的研究[D].南宁:广西医科大学,2015.
[20]Lai QG,Sun SL,Zhou XH,et al.Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis.J Zhejiang Univ Sci B.2014;15(5):482-490.
[21]Alkaisi A,Ismail AR,Mutum SS,et al.Transplantation of human dental pulp stem cells:enhance bone consolidation in mandibular distraction osteogenesis.J Oral Maxillofac Surg.2013;71(10):1758.e1-13.
[22]Ma D,Ren L,Yao H,et al.Locally injection of cell sheet fragments enhances new bone formation in mandibular distraction osteogenesis:a rabbit model.J Orthop Res.2013;31(7):1082-108.
[23]Deshpande SS,Gallagher KK,Donneys A,et al.Stem cell therapy remediates reconstruction of the craniofacial skeleton after radiation therapy.Stem Cells Dev.2013;22(11):1625-1632.
[24]Aykan A,Ozturk S,Sahin I,et al.Biomechanical analysis of the effect of mesenchymal stem cells on mandibular distraction osteogenesis.J Craniofac Surg.2013;24(2):e169-175.
[25]Sun Z,Tee BC,Kennedy KS,et al.Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis:preliminary studies in a porcine model.PLoS One.2013;8(9):e74672.
[26]Kim IS,Cho TH,Lee ZH,et al.Bone regeneration by transplantation of human mesenchymal stromal cells in a rabbit mandibular distraction osteogenesis model.Tissue Eng Part A.2013;19(1-2):66-78.
[27]周诺,黄旋平,江献芳,等.骨形态发生蛋白-2基因修饰骨髓间充质干细胞复合对氧化聚乙烯和聚丙烯共聚物移植促进兔下颌骨牵张成骨的实验研究[J].华西口腔医学杂志,2013,31(3):247-252.
[28]黄旋平,周诺,杨媛媛,等.hBMP-2基因修饰自体BMSCs移植促进兔下颌骨牵张成骨新骨形成的X线分析[J].实用口腔医学杂志,2012,28(4):457-460.
[29]Zhang WB,Zheng LW,Chua DT,et al.Treatment of irradiated mandibles with mesenchymal stem cells transfected with bone morphogenetic protein 2/7.J Oral Maxillofac Surg.2012;70(7):1711-1176.
[30]Castro-Govea Y,Cervantes-Kardasch VH,Borrego-Soto G,et al.Human bone morphogenetic protein 2-transduced mesenchymal stem cells improve bone regeneration in a model of mandible distraction surgery.J Craniofac Surg.2012;23(2):392-396.
[31]Long J,Li P,Du HM,et al.Effects of bone morphogenetic protein2 gene therapy on new bone formation during mandibular distraction osteogenesis at rapid rate in rabbits.Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2011;112(1):50-57.
[32]Hwang YJ,Choi JY.Addition of mesenchymal stem cells to the scaffold of platelet-rich plasma is beneficial for the reduction of the consolidation period in mandibular distraction osteogenesis.JOral Maxillofac Surg.2010;68(5):1112-1124.
[33]Jiang X,Zou S,Ye B,et al.bFGF-Modified BMMSCs enhance bone regeneration following distraction osteogenesis in rabbits.Bone.2010;46(4):1156-1161.
[34]来庆国.OSX基因修饰的骨髓MSCs促进兔下颌骨牵张成骨的实验研究[D].济南:山东大学,2010.
[35]Hu J,Qi MC,Zou SJ,et al.Callus formation enhanced by BMP-7ex vivo gene therapy during distraction osteogenesis in rats.JOrthop Res.2007;25(2):241-251.
[36]Shao Z,Liu B,Peng Q,et al.Transplantation of osteoblast-like cells to the distracted callus in the rabbit mandible.Plast Reconstr Surg.2007;119(2):500-507.
[37]Qi M,Hu J,Zou S,et al.Mandibular distraction osteogenesis enhanced by bone marrow mesenchymal stem cells in rats.JCraniomaxillofac Surg.2006;34(5):283-289.
[38]戚孟春,胡静,邹淑娟,等.骨髓间充质干细胞移植促进大鼠下颌骨牵张成骨的实验研究[J].中国口腔颌面外科杂志,2005,3(2):151-154.
[39]Pearce AI,Richards RG,Milz S,et al.Animal models for implant biomaterial research in bone:a review.Eur Cell Mater.2007;13:1-10.
[40]Friedenstein AJ,Gorskaja JF,Kulagina NN.Fibroblast precursors in normal and irradiated mouse hematopoietic organs.Exp Hematol.1976;4(5):267-274.
[41]Isobe Y,Koyama N,Nakao K,et al.Comparison of human mesenchymal stem cells derived from bone marrow,synovial fluid,adult dental pulp,and exfoliated deciduous tooth pulp.Int J Oral Maxillofac Surg.2016;45(1):124-131.
[42]陈燕,李志刚.MSCs对兔下颌骨牵张成骨处OPG表达的影响[J].药物与人,2014,27(7):9-10.
[43]Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endothelial cells for angiogenesis.Science.1997;275(5302):964-967.
[44]Rozen N,Bick T,Bajayo A,et al.Transplanted blood-derived endothelial progenitor cells(EPC)enhance bridging of sheep tibia critical size defects.Bone.2009;45(5):918-924.
[45]Halvorsen YD,Franklin D,Bond AL,et al.Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells.Tissue Eng.2001;7(6):729-741.
[46]Mahmoudifar N,Doran PM.Osteogenic differentiation and osteochondral tissue engineering using human adipose-derived stem cells.Biotechnol Prog.2013;29(1):176-185.
[47]Gronthos S,Mankani M,Brahim J,et al.Postnatal human dental pulp stem cells(DPSCs)in vitro and in vivo.Proc Natl Acad Sci US A.2000;97(25):13625-13630.
[48]霍永标.乳牙牙髓干细胞库的构建及其研究进展[J].国际口腔医学杂志,2011,38(2):188-191.
[49]Wu W,Le AV,Mendez JJ,et al.Osteogenic performance of donor-matched human adipose and bone marrow mesenchymal cells under dynamic culture.Tissue Eng Part A.2015;21(9-10):1621-1632.
[50]Ceccarelli G,Bloise N,Mantelli M,et al.A comparative analysis of the in vitro effects of pulsed electromagnetic field treatment on osteogenic differentiation of two different mesenchymal cell lineages.Biores Open Access.2013;2(4):283-294.
[51]Kitoh H,Kitakoji T,Tsuchiya H,et al.Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases.Bone.2004;35(4):892-898.
[2]王良,李军,沈毅,等.虚拟手术辅助的血管化腓骨肌(皮)瓣行下颌骨精确重建[J].中国耳鼻咽喉颅底外科杂志,2016,22(3):220-224.
[3]张赛,张龙城.下颌骨缺损修复的研究进展[J].中国耳鼻咽喉颅底外科杂志,2017,23(2):177-181.
[4]邹霓.骨组织工程人工合成支架材料的研究现状[J].中国组织工程研究与临床康复,2008,12(23):4481-4484.
[5]Codivilla A.The classic:On the means of lengthening,in the lower limbs,the muscles and tissues which are shortened through deformity.1905.Clin Orthop Relat Res.2008;466(12):2903-2909.
[6]Ilizarov GA.The principles of the Ilizarov method.1988.Bull Hosp Jt Dis.1997;56(1):49-53.
[7]McCarthy JG,Schreiber J,Karp N,et al.Lengthening the human mandible by gradual distraction.Plast Reconstr Surg.1992;89(1):1-8;discussion 9-10.
[8]N?rholt SE,Jensen J,Schou S,et al.Complications after mandibular distraction osteogenesis:a retrospective study of 131patients.Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2011;111(4):420-427.
[9]Ai-Aql ZS,Alagl AS,Graves DT,et al.Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis.J Dent Res.2008;87(2):107-118.
[10]Khedr MS,Abdel Al SE,Osman MM,et al.The effect of electrical stimulation on mandibular distraction osteogenesis.Egyptian Journal of Oral&Maxillofacial Surgery.2011;2(2):41-49.
[11]Xie LK,Wangrangsimakul K,Suttapreyasri S,et al.A preliminary study of the effect of low intensity pulsed ultrasound on new bone formation during mandibular distraction osteogenesis in rabbits.Int J Oral Maxillofac Surg.2011;40(7):730-736.
[12]Wang L,Zhou S,Liu B,et al.Locally applied nerve growth factor enhances bone consolidation in a rabbit model of mandibular distraction osteogenesis.J Orthop Res.2006;24(12):2238-2245.
[13]Ma G,Zhao JL,Mao M,et al.Scaffold-Based Delivery of Bone Marrow Mesenchymal Stem Cell Sheet Fragments Enhances New Bone Formation In Vivo.J Oral Maxillofac Surg.2017;75(1):92-104.
[14]El Hadidi YN,El Kassaby M,El Fatah Ahmed SA,et al.Effect of Mesenchymal Stem Cell Application on the Distracted Bone Microstructure:An Experimental Study.J Oral Maxillofac Surg.2016;74(7):1463.e1-1463.e11.
[15]Zheutlin AR,Deshpande SS,Nelson NS,et al.Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis:A histomorphometric evaluation.Cytotherapy.2016;18(5):664-672.
[16]Zeng JJ,Guo P,Zhou N,et al.Treatment of large bone defects with a novel biological transport disc in non-vascular transport distraction osteogenesis.Int J Oral Maxillofac Surg.2016;45(5):670-677.
[17]冯桂娟,郑科,宋冬惠,等.Runt相关基因2修饰的骨髓间充质干细胞促进兔下颌骨牵张成骨的研究[J].华西口腔医学杂志,2016,34(2):125-129.
[18]Deshpande SS,Gallagher KK,Donneys A,et al.Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.Plast Reconstr Surg.2015;135(3):799-806.
[19]王亚茜.EPCs在犬下颌骨非血管化输送盘牵张成骨血管新生中的作用的研究[D].南宁:广西医科大学,2015.
[20]Lai QG,Sun SL,Zhou XH,et al.Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis.J Zhejiang Univ Sci B.2014;15(5):482-490.
[21]Alkaisi A,Ismail AR,Mutum SS,et al.Transplantation of human dental pulp stem cells:enhance bone consolidation in mandibular distraction osteogenesis.J Oral Maxillofac Surg.2013;71(10):1758.e1-13.
[22]Ma D,Ren L,Yao H,et al.Locally injection of cell sheet fragments enhances new bone formation in mandibular distraction osteogenesis:a rabbit model.J Orthop Res.2013;31(7):1082-108.
[23]Deshpande SS,Gallagher KK,Donneys A,et al.Stem cell therapy remediates reconstruction of the craniofacial skeleton after radiation therapy.Stem Cells Dev.2013;22(11):1625-1632.
[24]Aykan A,Ozturk S,Sahin I,et al.Biomechanical analysis of the effect of mesenchymal stem cells on mandibular distraction osteogenesis.J Craniofac Surg.2013;24(2):e169-175.
[25]Sun Z,Tee BC,Kennedy KS,et al.Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis:preliminary studies in a porcine model.PLoS One.2013;8(9):e74672.
[26]Kim IS,Cho TH,Lee ZH,et al.Bone regeneration by transplantation of human mesenchymal stromal cells in a rabbit mandibular distraction osteogenesis model.Tissue Eng Part A.2013;19(1-2):66-78.
[27]周诺,黄旋平,江献芳,等.骨形态发生蛋白-2基因修饰骨髓间充质干细胞复合对氧化聚乙烯和聚丙烯共聚物移植促进兔下颌骨牵张成骨的实验研究[J].华西口腔医学杂志,2013,31(3):247-252.
[28]黄旋平,周诺,杨媛媛,等.hBMP-2基因修饰自体BMSCs移植促进兔下颌骨牵张成骨新骨形成的X线分析[J].实用口腔医学杂志,2012,28(4):457-460.
[29]Zhang WB,Zheng LW,Chua DT,et al.Treatment of irradiated mandibles with mesenchymal stem cells transfected with bone morphogenetic protein 2/7.J Oral Maxillofac Surg.2012;70(7):1711-1176.
[30]Castro-Govea Y,Cervantes-Kardasch VH,Borrego-Soto G,et al.Human bone morphogenetic protein 2-transduced mesenchymal stem cells improve bone regeneration in a model of mandible distraction surgery.J Craniofac Surg.2012;23(2):392-396.
[31]Long J,Li P,Du HM,et al.Effects of bone morphogenetic protein2 gene therapy on new bone formation during mandibular distraction osteogenesis at rapid rate in rabbits.Oral Surg Oral Med Oral Pathol Oral Radiol Endod.2011;112(1):50-57.
[32]Hwang YJ,Choi JY.Addition of mesenchymal stem cells to the scaffold of platelet-rich plasma is beneficial for the reduction of the consolidation period in mandibular distraction osteogenesis.JOral Maxillofac Surg.2010;68(5):1112-1124.
[33]Jiang X,Zou S,Ye B,et al.bFGF-Modified BMMSCs enhance bone regeneration following distraction osteogenesis in rabbits.Bone.2010;46(4):1156-1161.
[34]来庆国.OSX基因修饰的骨髓MSCs促进兔下颌骨牵张成骨的实验研究[D].济南:山东大学,2010.
[35]Hu J,Qi MC,Zou SJ,et al.Callus formation enhanced by BMP-7ex vivo gene therapy during distraction osteogenesis in rats.JOrthop Res.2007;25(2):241-251.
[36]Shao Z,Liu B,Peng Q,et al.Transplantation of osteoblast-like cells to the distracted callus in the rabbit mandible.Plast Reconstr Surg.2007;119(2):500-507.
[37]Qi M,Hu J,Zou S,et al.Mandibular distraction osteogenesis enhanced by bone marrow mesenchymal stem cells in rats.JCraniomaxillofac Surg.2006;34(5):283-289.
[38]戚孟春,胡静,邹淑娟,等.骨髓间充质干细胞移植促进大鼠下颌骨牵张成骨的实验研究[J].中国口腔颌面外科杂志,2005,3(2):151-154.
[39]Pearce AI,Richards RG,Milz S,et al.Animal models for implant biomaterial research in bone:a review.Eur Cell Mater.2007;13:1-10.
[40]Friedenstein AJ,Gorskaja JF,Kulagina NN.Fibroblast precursors in normal and irradiated mouse hematopoietic organs.Exp Hematol.1976;4(5):267-274.
[41]Isobe Y,Koyama N,Nakao K,et al.Comparison of human mesenchymal stem cells derived from bone marrow,synovial fluid,adult dental pulp,and exfoliated deciduous tooth pulp.Int J Oral Maxillofac Surg.2016;45(1):124-131.
[42]陈燕,李志刚.MSCs对兔下颌骨牵张成骨处OPG表达的影响[J].药物与人,2014,27(7):9-10.
[43]Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endothelial cells for angiogenesis.Science.1997;275(5302):964-967.
[44]Rozen N,Bick T,Bajayo A,et al.Transplanted blood-derived endothelial progenitor cells(EPC)enhance bridging of sheep tibia critical size defects.Bone.2009;45(5):918-924.
[45]Halvorsen YD,Franklin D,Bond AL,et al.Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells.Tissue Eng.2001;7(6):729-741.
[46]Mahmoudifar N,Doran PM.Osteogenic differentiation and osteochondral tissue engineering using human adipose-derived stem cells.Biotechnol Prog.2013;29(1):176-185.
[47]Gronthos S,Mankani M,Brahim J,et al.Postnatal human dental pulp stem cells(DPSCs)in vitro and in vivo.Proc Natl Acad Sci US A.2000;97(25):13625-13630.
[48]霍永标.乳牙牙髓干细胞库的构建及其研究进展[J].国际口腔医学杂志,2011,38(2):188-191.
[49]Wu W,Le AV,Mendez JJ,et al.Osteogenic performance of donor-matched human adipose and bone marrow mesenchymal cells under dynamic culture.Tissue Eng Part A.2015;21(9-10):1621-1632.
[50]Ceccarelli G,Bloise N,Mantelli M,et al.A comparative analysis of the in vitro effects of pulsed electromagnetic field treatment on osteogenic differentiation of two different mesenchymal cell lineages.Biores Open Access.2013;2(4):283-294.
[51]Kitoh H,Kitakoji T,Tsuchiya H,et al.Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases.Bone.2004;35(4):892-898.