大鼠骨髓基质干细胞与肌腱细胞在体外间接共培养的实验研究
摘要
目的肌腱病的治疗是临床骨科的难点,骨髓基质干细胞的应用为肌腱病的治疗提供了新思路。骨髓基质干细胞具有多向分化潜能并可以被诱导分化为多种细胞,但由于骨髓基质干细胞的分化机制及在治疗过程中的作用方式尚未明确,限制了其在肌腱病治疗中的应用。本课题通过体外构建骨髓基质干细胞与自体肌腱细胞的间接共培养体系,在单纯间接共培养环境下与间接共培养同时添加自体富血小板血浆进行干预的情况下研究间接共培养环境对骨髓基质干细胞的分化诱导作用,以探索骨髓基质干细胞的分化机制并为骨髓基质干细胞在肌腱病治疗中的应用提供参考。
方法应用组织块培养法分离培养大鼠肌腱细胞。体外采集大鼠骨髓基质干细胞并扩增。采集大鼠血液制备富血小板血浆并激活以获取富血小板血浆萃取液。利用孔径0.4μm的细胞共培养嵌盒与6孔板构建培养液相通但细胞不直接接触的间接共培养体系。将生长状态良好的第三代(P3)大鼠肌腱细胞及第四代大鼠骨髓基质干细胞(P4)用于实验,实验组骨髓基质干细胞被接种于间接共培养体系外室,将同体肌腱细胞种植于内室,另外单独设置一组间接共培养组并加入富血小板血浆萃取液。于间接共培养后第3天、第7天及第10天,分别提取各组间接共培养体系内外室的细胞进行形态学观察,并利用RT-PCR及免疫组化染色技术分别对各组肌腱细胞与骨髓基质干细胞的Ⅰ型胶原与腱调蛋白(TNMD)进行基因层面与蛋白层面的检测,以分析间接共培养环境对骨髓基质干细胞分化与细胞外基质表达的影响。
结果应用组织块培养法成功分离出细胞,并经鉴定证实为肌腱细胞。应用肌腱细胞与骨髓基质干细胞间接共培养3天后,间接共培养组的骨髓基质干细胞在RT-PCR检测与免疫组化染色检测中均未表达Ⅰ型胶原与腱调蛋白(TNMD)。间接共培养7天后,间接共培养组干细胞在Ⅰ型胶原的PCR电泳图像中出现模糊条带,同时Ⅰ型胶原免疫组化显示部分细胞呈弱阳性染色,单纯间接共培养组与富血小板血浆干预组之间结果无显著差异。间接共培养组干细胞在各种检测中未出现对腱调蛋白(TNMD)的表达。间接共培养10天后,间接共培养组干细胞在Ⅰ型胶原的PCR电泳图像中出现清晰条带,但亮度低于肌腱细胞对照组。同时Ⅰ型胶原免疫组化显示间接共培养组干细胞呈广泛弱阳性染色,通过测定免疫组化结果的平均光密度进行统计学分析,结果显示间接共培养组骨髓基质干细胞Ⅰ型胶原表达量显著高于干细胞阴性对照组,但低于肌腱细胞对照组。间接共培养组干细胞在腱调蛋白(TNMD)的PCR电泳图像中表现为模糊条带,但腱调蛋白(TNMD)免疫组化染色结果为阴性。
结论通过组织块培养法可以在体外成功分离并培养大鼠肌腱细胞。与肌腱细胞间接共培养的培养环境可以诱导骨髓基质干细胞表达Ⅰ型胶原。间接共培养环境下骨髓基质干细胞未出现明显的腱调蛋白表达。根据实验结果,不能认为富血小板血浆的干预对间接共培养环境诱导后骨髓基质干细胞细胞外基质的分泌产生影响。尚不能认为间接共培养环境可以诱导骨髓基质干细胞向肌腱细胞分化。
Objective:How to treat tendinopathy is a Clinical difficulty. The application of bone marrow mesenchymal cells(BMSCs) in treating tendinopathy is a novel method which has already lead to some positive results. BMSCs have the multipotentials of differentiation into various cell types,but both of the mechanism of differentiation and the role BMSCs plays in the therapeutic process are poorly understood and because of which the scientific and Clinical application of BMSCs has been restricted. We were trying to build an indirect coculture system to investigate differentiation of BMSCs induced by indirect coculturing with tenocytes. comparison was also made between the simple coculture group and the coculture group with platelet-rich plasma added to study the effects of platelet-rich plasma to BMSCs on secretion of extracellular matrix when being inducted by indirect coculture with tenocytes. On this basis we could explore the mechanism of differentiation and making a reference for Clinical application of BMSCs in treatment of tendinopathy.
Methods:Tenocytes of SD rats were isolated using explant cuture method.BMSCs were collected using adherence screening method. Autolo-gous platelet-rich plasma was prepared. An indirect coculture system was established using transwell(0.4μm pore size) to inhibiting migration of cells and direct contact.The BMSCs(P4) and tenocytes (P3) were collected, BMSCs were placed in the outer chamber of this system and tenocytes in the inner chamber, one additional PRP added indirect coculture group was set up. The mRNA expression of TNMD and typeⅠcollagen were measured by RT-PCR and the corresponding protein levels of TNMD and typeⅠcollagen by technique of immunohistochemistry at various time points (3d,7d,10d) to study the secretion of extracellular matrix and differentiation of BMSCs induced by the coculture envioroment.
Results:Cells were isolated using tendon explant cuture and proved to be tenocytes.There is no significant TNMD nor typeⅠcollagen expresssion observed 3days after coculture. Indistinc bands were observed on the PCR image detecting typeⅠcollagen expression by BMSCs in coculture enciroment and some of BMSCs were stained by immunohistochemical staining 7days later.TNMD expression of BMSCs in coculture enciroment was not observed.On the 10th day after coculture,distinct bands were observed on the PCR image detecting typeⅠcollagen expression by BMSCs in coculture enciroment and BMSCs of experimental groups were widely stained by immunohistochemical staining.Mean optical density(MOD)of the results of immunohistochemical staining were measured for statistical analysis.The statistical data showed that experimental groups had a higher typeⅠcollagen expression than the negative control but lower than the positive control.During the experimental groups, there is no marked qualitative difference between the simple coculture group and PRP group.There is indistinct bands on the PCR image detecting TNMD expression by BMSCs in coculture enciroment,the result of TNMD immuno-histochemical staining is negative.
Conclusions:Tenocytes of SD rats could be successfully isolated using explant cuture method.The typeⅠCollagen expression of BMSCs could be induced by the enviroment of being cocultured with tenocytes.No significant TNMD expression of BMSCs was observed after coculture process.There is no significant effect of PRP to the secretion of extracellular matrix of BMSCs in the enviroment of coculture.There is not enough evidence to prove that BMSCs could differentiate into tenocytes after being induced by the inviroment of coculture.
方法应用组织块培养法分离培养大鼠肌腱细胞。体外采集大鼠骨髓基质干细胞并扩增。采集大鼠血液制备富血小板血浆并激活以获取富血小板血浆萃取液。利用孔径0.4μm的细胞共培养嵌盒与6孔板构建培养液相通但细胞不直接接触的间接共培养体系。将生长状态良好的第三代(P3)大鼠肌腱细胞及第四代大鼠骨髓基质干细胞(P4)用于实验,实验组骨髓基质干细胞被接种于间接共培养体系外室,将同体肌腱细胞种植于内室,另外单独设置一组间接共培养组并加入富血小板血浆萃取液。于间接共培养后第3天、第7天及第10天,分别提取各组间接共培养体系内外室的细胞进行形态学观察,并利用RT-PCR及免疫组化染色技术分别对各组肌腱细胞与骨髓基质干细胞的Ⅰ型胶原与腱调蛋白(TNMD)进行基因层面与蛋白层面的检测,以分析间接共培养环境对骨髓基质干细胞分化与细胞外基质表达的影响。
结果应用组织块培养法成功分离出细胞,并经鉴定证实为肌腱细胞。应用肌腱细胞与骨髓基质干细胞间接共培养3天后,间接共培养组的骨髓基质干细胞在RT-PCR检测与免疫组化染色检测中均未表达Ⅰ型胶原与腱调蛋白(TNMD)。间接共培养7天后,间接共培养组干细胞在Ⅰ型胶原的PCR电泳图像中出现模糊条带,同时Ⅰ型胶原免疫组化显示部分细胞呈弱阳性染色,单纯间接共培养组与富血小板血浆干预组之间结果无显著差异。间接共培养组干细胞在各种检测中未出现对腱调蛋白(TNMD)的表达。间接共培养10天后,间接共培养组干细胞在Ⅰ型胶原的PCR电泳图像中出现清晰条带,但亮度低于肌腱细胞对照组。同时Ⅰ型胶原免疫组化显示间接共培养组干细胞呈广泛弱阳性染色,通过测定免疫组化结果的平均光密度进行统计学分析,结果显示间接共培养组骨髓基质干细胞Ⅰ型胶原表达量显著高于干细胞阴性对照组,但低于肌腱细胞对照组。间接共培养组干细胞在腱调蛋白(TNMD)的PCR电泳图像中表现为模糊条带,但腱调蛋白(TNMD)免疫组化染色结果为阴性。
结论通过组织块培养法可以在体外成功分离并培养大鼠肌腱细胞。与肌腱细胞间接共培养的培养环境可以诱导骨髓基质干细胞表达Ⅰ型胶原。间接共培养环境下骨髓基质干细胞未出现明显的腱调蛋白表达。根据实验结果,不能认为富血小板血浆的干预对间接共培养环境诱导后骨髓基质干细胞细胞外基质的分泌产生影响。尚不能认为间接共培养环境可以诱导骨髓基质干细胞向肌腱细胞分化。
Objective:How to treat tendinopathy is a Clinical difficulty. The application of bone marrow mesenchymal cells(BMSCs) in treating tendinopathy is a novel method which has already lead to some positive results. BMSCs have the multipotentials of differentiation into various cell types,but both of the mechanism of differentiation and the role BMSCs plays in the therapeutic process are poorly understood and because of which the scientific and Clinical application of BMSCs has been restricted. We were trying to build an indirect coculture system to investigate differentiation of BMSCs induced by indirect coculturing with tenocytes. comparison was also made between the simple coculture group and the coculture group with platelet-rich plasma added to study the effects of platelet-rich plasma to BMSCs on secretion of extracellular matrix when being inducted by indirect coculture with tenocytes. On this basis we could explore the mechanism of differentiation and making a reference for Clinical application of BMSCs in treatment of tendinopathy.
Methods:Tenocytes of SD rats were isolated using explant cuture method.BMSCs were collected using adherence screening method. Autolo-gous platelet-rich plasma was prepared. An indirect coculture system was established using transwell(0.4μm pore size) to inhibiting migration of cells and direct contact.The BMSCs(P4) and tenocytes (P3) were collected, BMSCs were placed in the outer chamber of this system and tenocytes in the inner chamber, one additional PRP added indirect coculture group was set up. The mRNA expression of TNMD and typeⅠcollagen were measured by RT-PCR and the corresponding protein levels of TNMD and typeⅠcollagen by technique of immunohistochemistry at various time points (3d,7d,10d) to study the secretion of extracellular matrix and differentiation of BMSCs induced by the coculture envioroment.
Results:Cells were isolated using tendon explant cuture and proved to be tenocytes.There is no significant TNMD nor typeⅠcollagen expresssion observed 3days after coculture. Indistinc bands were observed on the PCR image detecting typeⅠcollagen expression by BMSCs in coculture enciroment and some of BMSCs were stained by immunohistochemical staining 7days later.TNMD expression of BMSCs in coculture enciroment was not observed.On the 10th day after coculture,distinct bands were observed on the PCR image detecting typeⅠcollagen expression by BMSCs in coculture enciroment and BMSCs of experimental groups were widely stained by immunohistochemical staining.Mean optical density(MOD)of the results of immunohistochemical staining were measured for statistical analysis.The statistical data showed that experimental groups had a higher typeⅠcollagen expression than the negative control but lower than the positive control.During the experimental groups, there is no marked qualitative difference between the simple coculture group and PRP group.There is indistinct bands on the PCR image detecting TNMD expression by BMSCs in coculture enciroment,the result of TNMD immuno-histochemical staining is negative.
Conclusions:Tenocytes of SD rats could be successfully isolated using explant cuture method.The typeⅠCollagen expression of BMSCs could be induced by the enviroment of being cocultured with tenocytes.No significant TNMD expression of BMSCs was observed after coculture process.There is no significant effect of PRP to the secretion of extracellular matrix of BMSCs in the enviroment of coculture.There is not enough evidence to prove that BMSCs could differentiate into tenocytes after being induced by the inviroment of coculture.
引文
1. Kujala UM, Sarna S, Kaprio J. Cumulative incidence of achilles tendon rupture and tendinopathy in male former elite athletes.Clin J Sport Med. 2005;15:133-135.
2. Murray IR, Murray SA, MacKenzie K, coleman S. How evidence based is the management of two common sports injuries in a sports injury Clinic? Br J Sports Med.2005;39:912-916;
3. Maffulli N, Wong J, Almekinders LC. Types and epidemiology of tendinopathy. Clin Sports Med.2003;22(4):675-692.
4.4.P. Sharmal and N. Maffulli, Biology of tendon injury:healing,modeling and remodeling.J Musculoskelet Neuronal Interact 2006; 6(2):181-190
5. Evgenia Karousou, Mario Ronga,Davide Vigetti, Alberto Passi,Nicola Maffulli, FRCS, collagens, Proteoglycans, MMP-2, MMP-9 and TIMPs in Human Achilles Tendon Rupture, Clin Orthop Relat Res (2008) 466:1577-1582.
6. Pankaj Sharma and Nicola Maffulli,Tendon Injury and Tendinopathy:Healing and Repair.J Bone Joint Surg Am,2005;87:187-202.
7. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med.2006;10(10):1-5.
8. Edwards SG, Calandruccio JH. Autologous blood injections for refractory lateral epicondylitis. Am J Hand Surg.2003;28(2):272-8.
9. Kannus P, Jozsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am.1991; 73:1507-1525.
10. Scott A, Khan KM, Heer J, cook JL, Lian O, Duronio V. High strain mechanical loading rapidly induces tendon apoptosis:an ex vivo rat tibialis anterior model. Br J Sports Med.2005;39:e25.
11. Wang F, Murrell GA, Wang MX. Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression. J Orthop Res.2007;25:378-389.
12. Bosman, F. T. and Stamenkovic, I.2003. Functional structure and composition of the extracellular matrix. J. Pathol.200:423-428.
13.13.de Mos M, van E1 B, DeGroot J, Jahr H, van Schie H, van Arkel E, Tol H, KHeijboer R, van Osch G, Verhaar J. Achilles tendinosis:changes in biochemical composition and collagen turnover rate. Am J Sports Med.2007; 35:1549-1556.
14. Lian, Dahl J, Ackermann PW, Frihagen F, Engebretsen I, Bahr R.Prono-ciceptive and antinociceptive neuromediators in patellar tendinopathy.Am J Sports Med.2006;34:1801-1808.
15. Lui PP, Chan LS, Fu SC, Chan KM.,Expression of Sensory Neuropeptides in Tendon Is Associated With Failed Healing and Activity-Related Tendon Pain in collagenase-Induced Tendon Injury. Am J Sports Med.2010 Apr;38(4): 757-64. Epub 2010 Feb 5.
16. Ziche M, Morbidelli L, Pacini M, Geppetti P, Alessandri G, Maggi CA. Substance P stimulates neovascularisation in vivo and proliferation of cultured endothelial cells. Microvasc Res.1990;40:
17. Alfredson H, Lorentzon R. Chronic tendon pain:no signs of chemical inflammation but high concentrations of the neurotransmitter glutamate. Implications for treatment? Curr Drug Targets.2002;3:43-54.
18. Schubert TE, Weidler C, Lerch K, et al. Achilles tendinosis is associated with sprouting of substance P positive nerve fibres. Ann Rheum Dis 2005 Jul;64:1083
19. K. M. Heinemeier, J. L. Olesenl, F. Haddad, H. Langbergl, M. Kjaerl, K. M. Baldwin and P. Schjerling,Expression of collagen and related growth factors in rat tendon and skeletal musCle in response to specific contraction types. J Physiol 582.3 (2007) pp 1303-1316
20.20.Scott A, Lian 0, Bahr R, Hart DA, Duronio V, Khan KM. Br J Sports Med. Increased mast cell numbers in human patellar tendinosis:correlation with symptom duration and vascular hyperplasia.2008 Sep;42(9):753-7.
21. Yinghua Xu MBBS, George A. C. Murrell MD, Dphil, The Basic Science of Tendinopathy Clin Orthop Relat Res (2008) 466:1528-1538.
22. Krishna R. Asundi,Karen B. King,David M.Rempel,Evaluation of gene expression through qRT-PCR in cyClically loaded tendons:an in vivo model,Eur J Appl Physiol (2008) 102:265-270
23. Andres BM, Murrell GA.,Treatment of Tendinopathy:What Works, What Does Not, and What is on the Horizon. Clin Orthop Relat Res.2008 Jul;466(7):1539-54.
24. Kader D, Sakena A, Movin T, Magulli N. Achilles tendinopathy:some aspects of basic science and Clinical management. Br J Sports Med.2002;36:239-49.
25. Roos EM, Engstrom M, Lagerquist A, et al. Clinical improvement after 6 weeks of eccentric exercise in patients with mid-portion Achilles tendino-pathy-a randomized trial with 1-year follow-up. Scand J Med Sci Sports. 2004;14:286-295.
26. Silbernagel KG, Thomee R, Eriksson BI. continued sports activity,using a pain-monitoring model, during rehabilitation in patients with Achilles tendinopathy:a randomized controlled study. Am J Sports Med.2007; 35: 897-906.
27. Zelle BA, Gollwitzer H, Zlowodzki M, Buhren V. Extracorporeal shock wave therapy: current evidence. J Orthop Trauma.2010 Mar;24 Suppl 1:S66-70.
28. Van Leeuwen MT, Zwerver J, Akker-Scheek I:Extracorporeal shockwave therapy for patellar tendinopathy:a review of the literature. Br J Sports Med 2009,43:163-168.
29. Johannes Zwerver, Evert Verhagen, Fred Hartgens, Inge van den Akker-Scheek, Ron L Diercks, Zwerver.The Topgame-study:effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy. Design of a randomised controlled trial Musculoskeletal Disorders. BMC Musculoskelet Disord.2010 Feb 8;11:28.
30. Smidt N, Assendelft W, Arola H. Effectiveness of physiotherapy for lateral epicondylitis:a systemic review. Ann Med.2003;35:51-62.
31. Jobe F, Ciccotti M. Lateral and medial epicondylitis of the elbow. J Am Acad Orthop Surg.1994;2:1-8.
32.32.C Gaujoux-Viala, M Dougados, and L Gossec, Efficacy and safety of steroid injections for shoulder and elbow tendonitis:a meta-analysis of randomised controlled trials, Ann Rheum Dis.2009 December; 68(12): 1843-1849.
33. Martin Clementson,Ingemar Lore'n (?)E Leif Dahlberg,Mats A strom. SClerosing injections in midportion Achilles tendinopathy:a retrospective study of 25 patients, Knee Surg Sports Traumatol Arthrosc (2008) 16:887-890
34. Lake JE, Ishikawa SN.conservative treatment of Achilles tendinopathy: emerging techniques. Foot Ankle Clin.2009 Dec;14(4):663-74.
35. collen A, Hanemaaijer R, Lupu F, Quax P, van Lent N, Grimbergen J, Peters E, Koolwijk P, van Hinsbergh V. Membrane-type maxtrix metelloproteinase mediated angiogenesis in a fibrin-collagen matrix. Blood.2003; 101: 1810-1817.
36.36.R Brown, J Orchard, M Kinchington, A Hooper, G Nalder Aprotinin in the management of Achilles tendinopathy:a randomised controlled trial. Br J Sports Med 2006; 40:275-279.
37. John OrchardAndrew Massey,Richard Brown,Ade'line Cardon-Dunbar, Jamie Hofmann,Successful Management of Tendinopathy With Injections of the MMP-inhibitor Aprotinin, Clin Orthop Relat Res (2008) 466:1625-1632
38. Dietrich W, Spath P, ZuhlSDorf M, et al. Anaphylactic reactions of aprotinin reexposure in cardiac surgery:relation to antiaprotinin immunoglobulin G and E antibodies. Anesthesiology.2001;95:64-71.
39. Orchard J, Massey A, Rimmer J, Hofman J, Brown R. Delay of 6 weeks between aprotinin injections for tendinopathy reduces risk of allergic reaction. J Sci Med Sport.2007:Aug 11 epub
40. Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ., Mesenchymal Stem Cells and Insulin-Like Growth Factor-Ⅰ Gene-Enhanced Mesenchymal Stem Cells Improve Structural Aspects of Healing in Equine Flexor Digitorum Superficialis Tendons J Orthop Res.2009 Oct;27(10):1392-8.
41. Wang XT, Liu PY, Tang JB. Tendon healing in vitro:Genetic modification of tenocytes with exogenous PDGF gene and promotion of collagen gene expression. J Hand Surg (Am) 2004;29(5):884-890.
42. Liu Q, Muruve DA. Molecular basis of the inflammatory response to adenovirus vectors. Gene Ther.2003 Jun; 10(11):935-40.
43. Kryger GS, Chong AK, costa M, Pham H, Bates SJ, Chang J. A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. J Hand Surg Am.2007 May-Jun;32(5):597-605.
44. Juncosa-Melvin N, Boivin GP, Gooch C, Galloway MT, West JR, Dunn MG, Butler DL. The effect of autologous mesenchymal stem cells on the biomechanics and histology of gelcollagen sponge constructs used for rabbit patellar tendon repair.Tissue Eng.2006;12:369-379.
45. Soon MY, Hassan A, Hui JH, Goh JC, Lee EH. An analysis of soft tissue allograft anterior cruciate ligament reconstruction in a rabbit model:a short-term study of the use of mesenchymal stem cells to enhance tendon osteointegration. Am J Sports Med.2007;35:962-971.
46. Chong AK, Ang AD, Goh JC, Hui JH, Lim AY, Lee EH, Lim BH. Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model. J BoneJoint Surg Am.2007;89:74-81.
47. Lacitignola, Crovace. Rossi, Francioso,Cell therapy for tendinitis, experimental and Clinical report.Vet Res commun 2008; 32 (Suppll):S33-S38
48. ROGER K. W. SMITH, Mesenchymal stem cell therapy for equine tendinopathy.Disability and Rehabilitation,2008; 30(20-22):1752-1758.
49. Richardson LE, Dudhia J, Sadler CJ, Goodship AE, Smith RKW. Extracellular matrix cues for mesenchymal stem cell differentiation. Proceedings of the 53rd Orthopaedic Research Society 2007;32:472.
50. 聂继乎,温树正,细胞生长因子在肌腱修复中作用的研究进展.《医学综述》。2008年14卷1期：11-13页。
51. Anitua M, Sa'nchez E, Nurden A, Nurden P, Orive G, Andi'a I.New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol.2006; 24(5):227-34.
52. Brandon P. Donnelly, BS; Alan J. Nixon, BVSc, MS; Jennifer L. Haupt, BS; Linda A. Dahlgren,NuCleotide structure of equine platelet-derived growth factor-A and -B and expression in horses with induced acute tendinitis.Am J Vet Res.2006 Jul;67(7):1218-25.
53. Everts P, Knape J, Weirich G, Schonberger J, Hoffman J, Overdevest E. Platelet- rich plasma and platelet gel:a review. JECT.2006;38:174-87.
54. Rolf CG, Fu BS, Pau A, Wang W, Chan B.Increased cell proliferation and associated expression of PDGFRbeta causing hypercellularity in patellar tendinosis. Rheumatology Oxford.2001 Mar;40(3):256-61.
55. Ranly D, Lohmann C, Andreacchio D, Boyan B, Schwartz Z. Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in nude mice. J Bone Joint Surg.2007;89.
56. Sharma P, Maffulli N.,Tendinopathy and tendon injury:The future, Disability and Rehabilitation,2008; 30(20-22):1733-1745)139-46.
57. Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers.2006 Nov;10(4):515-27
58. Scott A, Lian 0, Bahr R, Hart DA, Duronio V., VEGF expression in patellar tendinopathy:a preliminary study. Clin Orthop Relat Res.2008 Jul;466(7): 598-604. Epub 2008 May 6.
59. Danielson P, Alfredson H, Forsgren S, Distribution of general (PGP 9.5) and sensory (substance P/CGRP) innervations in the human patellar tendon.Knee Surg Sports Traumatol Arthrosc.2006 Feb; 14(2):125-32. Epub 2005 Jun 28.
60.60.Antitua E, Andia I, Sanchez M, Azofra J, Del Mar Zalduendo M,De La Fuente M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF productions by human tendon cells in culture. J Orthop Res.2005;23:281-6.
61. 任强,黄昌林,郭振海,兔跟腱修复过程中胰岛素样生长因子-Ⅰ的表达,Journal of zhengzhou University(Medical Sciences)Nov.2005; Vol40 No.6
62. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med.2003; 33(5):381-94.
63. Banes AJ, Horesovsky G, Larson C, Tsuzaki M, Judex S,A rchambault J, et al. Mechanical load stimulates expression of novel genes in vivo and in vitro in avian flexor tendon cells.Osteoarth Cartilage 1999;7:141-153.
64. 宋德业,倪江东,体外培养肌腱细胞增殖与碱性成纤维细胞,医学临床研2007年8月第24卷第8期
65. Sheng J, Zeng B, Jiang P. Effects of exogenous basic fibroblast in-sheathed tendon healing and adhesion, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007 Jul;21(7):733-7.
66. Marx R, Garg A. Dental and craniofacial applications of plateletrich plasma.出版社：Quintessence Publishing company,出版日期：2005年1月
67. Everts P, Knape J, Weirich G, Schonberger J, Hoffman J,Overdevest E, et al. Platelet-rich plasma and platelet gel:a review. JECT.2006;38:174-87.
68. Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N.. Autologous platelet rich plasma for arthroscopic rotator cuff repair.:A pilot study. Disabil Rehabil. 2008; 30(20-22):1584-9.
69. 余情,陈统一,创伤后富血小板血浆治疗研究进展,国际骨科学杂志,2008年7月第29卷第4期
70. Allan Mishra, Padmaja Tummala, Aaron King, Byung Lee, Mark Kraus,Victor Tse, Christopher R.Jacobs, Buffered Platelet-Rich Plasma Enhances Mesenchymal Stem Cell Proliferation and Chondrogenic Differentiation. TISSUE ENGINEERING:Part C Volume 15, Number 00,2009
71. E. Anitua, M. Sanchez, M. M. Zalduendo, M. de la Fuente, R. Prado, G. Orive and I. Andia.Fibroblastic response to treatment with different preparations rich in growth factors. Cell Prolif.2009 Apr;42(2):162-70. Epub 2009 Feb 24.
72. Moon YL, Jo SH, Song CH, Park G, Lee HJ, Jang SJ.Autologous Bone Marrow Plasma Injection after Arthroscopic Debridementfor Elbow Tendinosis. Ann Acad Med Singapore.2008;Jul;37(7):559-63.
73. Gardner MJ, Demetrakopoulos D, Klepchick P, Mooar P. The efficacy of autologous platelet gel in pain control and blood loss in total knee arthroplasty:an analysis of the haemoglobin, narcotic requirement and range of motion. Int Orthop.2006;31:309-13.
74. Berghoff W, Pietrzak W, Rhodes R. Platelet-rich plasma applicationduring Closure following total knee arthroplasty.Orthopedics.2006;29(7):590-8.
75. Kajikawa Y, Morihara T, Sakamoto H, Matsuda K, Oshima Y,Yoshida A, et al. Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing. J Cell Physiol.2008;215(3):837-45.
76. Taylor M, Norman T, Clovis N, Blaha D. The response of rabbit patellar tendons after autologous blood injection. Med Sci Sports Exerc. 2002;34(1):70-3
77. de Vos RJ, van Veldhoven PL, Moen MH, Weir A, Tol JL, Maffulli N., Autologous growth factor injections in chronic tendinopathy:a systematic review. Br Med Bull.2010 Mar 2.
78. 陈琳,富含血小板血浆临床应用的优势,中国口腔种植学杂志2008年第13卷第3期
79. 张卫兵,洪光祥,康皓富。血小板血浆对兔骨髓间充质干细胞增殖的作用,中国组织工程研究与 1 临床康复第,12卷34期
1. Magnusson SP, Langberg H, Kjaer M. Nat Rev Rheumatol. The pathogenesis of tendinopathy:balancing the response to loading. Nat Rev Rheumatol.2010 May; 6(5):262-8. Epub 2010 Mar 23.
2. Sensebe L, Bourin P.Mesenchymal stem cells for therapeutic purposes. Transplantation.2009 May 15;87(9 Suppl):S49-53.
3. ROGER K. W. SMITH. Mesenchymal stem cell therapy for equine tendinopathy, Disability and Rehabilitation,2008; 30(20-22):1752-1758
4. Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ.Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons.J Orthop Res.2009 Oct; 27(10):1392-8.
5. Park JS, Hashi C, Li S.Culture of bone marrow mesenchymal stem cells on engineered matrix. Methods Mol Biol.2010;621:117-37.
6. Taralyn McCarrel, Lisa Fortier. Temporal Growth Factor Release from Platelet-Rich Plasma, Trehalose Lyophilized Platelets, and Bone Marrow Aspirate and Their Effect on Tendon and Ligament Gene Expression.Journal of orthopaedic research.2009 vol.27 no.8
7. Lacci KM, Dardik A. Platelet-rich plasma:support for its use in wound healing. Yale J Biol Med.2010 Mar;83(1):1-9.
8. Xiaobing CHENG,1 Delin LEI,1 Tianqiu MAO,1 Shuyong YANG.1 Fulin CHEN,2 Wei WU1 Repair of critical bone defects with injectable platelet rich plasma/bone marrow-derived stromal cells composite:experimental study in rabbits.Ulus Travma Acil Cerrahi Derg 2008;14(2):87-95
9. 黄谦吴涛金丹黄爱文江汕裴国献.不同比例激活富血小板血浆对其生长因子浓度及人骨髓基质干细胞增殖的影响.中华创伤骨科杂志2008年10月第10卷第10期
10.张卫兵,洪光祥,康皓富。血小板血浆对兔骨髓间充质干细胞增殖的作用,中国组织工程研究与 1 临床康复第,12卷34期
11. Wen-Fei Nia, Li-Hui Yinb,*, Jike Luc, Hua-Zi Xua, Yong-Long Chia, Jian-Bo Wub, Nu Zhangd In vitro neural differentiation of bone marrow stromal cells induced by cocultured olfactory ensheathing cells. Neurosci Lett.2010 Mar 27.
12. LI Zhuo, GU Tian-xiang and ZHANG Yu-hai. Hepatocyte growth factor Combined with insulin like growth factor-1 improves expression of GATA-4 in mesenchymal stem cells cocultured with cardiomyocytes Chin Med J 2008; 121(4):336-340
13. Richardson LE, Dudhia J, Sadler CJ, Goodship AE, Smith RKW. Extracellular matrix cues for mesenchymal stem cell differentiation. Proceedings of the 53rd OrthopaedicResearch Society 2007;32:472.
14. Magnusson SP, Langberg H, Kjaer M. The pathogenesis of tendinopathy: balancing the response to loading.Nat Rev Rheumatol.2010 May;6(5):262-8. Epub 2010 Mar 23
15. Sahoo S, Ang LT, Cho-Hong Goh J, Toh SL. Bioactive nanofibers for fibroblastic differentiation of mesenchymal precursor cells for ligament/tendon tissue engineering applications. Differentiation.2010 Feb;79(2):102-10. Epub 2009 Dec 5.
16.王锋,吴小涛,王运涛,李果,张明.非接触共培养条件下人BMSCs对氧化应激环境中退变髓核细胞凋亡的保护研究.中国修复重建外科杂志2010年4月第24卷第4期
17. P. Sharmal, N. Maffulli. Biology of tendon injury:healing, modeling and remodeling.L J Musculoskelet Neuronal Interact 2006; 6(2):181-190
18. Denitsa Docheva, Ernst B. Hunziker, Reinhard Fassler, Oliver Bandau. Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation. Molecular and cellular biology, Jan.2005, P699-705, Vol.25, No.2
19. Omae H, Zhao C, Sun YL, An KN, Amadio PC. Multilayer tendon slices seeded with bone marrow stromal cells:a novel composite for tendon engineering. J Orthop Res.2009 Jul;27(7):937-42.
20.许峰,刘伟,曹谊林.肌腱细胞的生物特性.《中华医学研究杂志》.2003年第3卷第11期
21.夏冰,王捷,郭立达,詹纯列,肖育华,杨传红.不同种属骨髓间充质干细胞体外培养特性的比较研究,中国微侵袭神经外科杂志2006年第11卷第12期：555-557
2. Murray IR, Murray SA, MacKenzie K, coleman S. How evidence based is the management of two common sports injuries in a sports injury Clinic? Br J Sports Med.2005;39:912-916;
3. Maffulli N, Wong J, Almekinders LC. Types and epidemiology of tendinopathy. Clin Sports Med.2003;22(4):675-692.
4.4.P. Sharmal and N. Maffulli, Biology of tendon injury:healing,modeling and remodeling.J Musculoskelet Neuronal Interact 2006; 6(2):181-190
5. Evgenia Karousou, Mario Ronga,Davide Vigetti, Alberto Passi,Nicola Maffulli, FRCS, collagens, Proteoglycans, MMP-2, MMP-9 and TIMPs in Human Achilles Tendon Rupture, Clin Orthop Relat Res (2008) 466:1577-1582.
6. Pankaj Sharma and Nicola Maffulli,Tendon Injury and Tendinopathy:Healing and Repair.J Bone Joint Surg Am,2005;87:187-202.
7. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med.2006;10(10):1-5.
8. Edwards SG, Calandruccio JH. Autologous blood injections for refractory lateral epicondylitis. Am J Hand Surg.2003;28(2):272-8.
9. Kannus P, Jozsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am.1991; 73:1507-1525.
10. Scott A, Khan KM, Heer J, cook JL, Lian O, Duronio V. High strain mechanical loading rapidly induces tendon apoptosis:an ex vivo rat tibialis anterior model. Br J Sports Med.2005;39:e25.
11. Wang F, Murrell GA, Wang MX. Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression. J Orthop Res.2007;25:378-389.
12. Bosman, F. T. and Stamenkovic, I.2003. Functional structure and composition of the extracellular matrix. J. Pathol.200:423-428.
13.13.de Mos M, van E1 B, DeGroot J, Jahr H, van Schie H, van Arkel E, Tol H, KHeijboer R, van Osch G, Verhaar J. Achilles tendinosis:changes in biochemical composition and collagen turnover rate. Am J Sports Med.2007; 35:1549-1556.
14. Lian, Dahl J, Ackermann PW, Frihagen F, Engebretsen I, Bahr R.Prono-ciceptive and antinociceptive neuromediators in patellar tendinopathy.Am J Sports Med.2006;34:1801-1808.
15. Lui PP, Chan LS, Fu SC, Chan KM.,Expression of Sensory Neuropeptides in Tendon Is Associated With Failed Healing and Activity-Related Tendon Pain in collagenase-Induced Tendon Injury. Am J Sports Med.2010 Apr;38(4): 757-64. Epub 2010 Feb 5.
16. Ziche M, Morbidelli L, Pacini M, Geppetti P, Alessandri G, Maggi CA. Substance P stimulates neovascularisation in vivo and proliferation of cultured endothelial cells. Microvasc Res.1990;40:
17. Alfredson H, Lorentzon R. Chronic tendon pain:no signs of chemical inflammation but high concentrations of the neurotransmitter glutamate. Implications for treatment? Curr Drug Targets.2002;3:43-54.
18. Schubert TE, Weidler C, Lerch K, et al. Achilles tendinosis is associated with sprouting of substance P positive nerve fibres. Ann Rheum Dis 2005 Jul;64:1083
19. K. M. Heinemeier, J. L. Olesenl, F. Haddad, H. Langbergl, M. Kjaerl, K. M. Baldwin and P. Schjerling,Expression of collagen and related growth factors in rat tendon and skeletal musCle in response to specific contraction types. J Physiol 582.3 (2007) pp 1303-1316
20.20.Scott A, Lian 0, Bahr R, Hart DA, Duronio V, Khan KM. Br J Sports Med. Increased mast cell numbers in human patellar tendinosis:correlation with symptom duration and vascular hyperplasia.2008 Sep;42(9):753-7.
21. Yinghua Xu MBBS, George A. C. Murrell MD, Dphil, The Basic Science of Tendinopathy Clin Orthop Relat Res (2008) 466:1528-1538.
22. Krishna R. Asundi,Karen B. King,David M.Rempel,Evaluation of gene expression through qRT-PCR in cyClically loaded tendons:an in vivo model,Eur J Appl Physiol (2008) 102:265-270
23. Andres BM, Murrell GA.,Treatment of Tendinopathy:What Works, What Does Not, and What is on the Horizon. Clin Orthop Relat Res.2008 Jul;466(7):1539-54.
24. Kader D, Sakena A, Movin T, Magulli N. Achilles tendinopathy:some aspects of basic science and Clinical management. Br J Sports Med.2002;36:239-49.
25. Roos EM, Engstrom M, Lagerquist A, et al. Clinical improvement after 6 weeks of eccentric exercise in patients with mid-portion Achilles tendino-pathy-a randomized trial with 1-year follow-up. Scand J Med Sci Sports. 2004;14:286-295.
26. Silbernagel KG, Thomee R, Eriksson BI. continued sports activity,using a pain-monitoring model, during rehabilitation in patients with Achilles tendinopathy:a randomized controlled study. Am J Sports Med.2007; 35: 897-906.
27. Zelle BA, Gollwitzer H, Zlowodzki M, Buhren V. Extracorporeal shock wave therapy: current evidence. J Orthop Trauma.2010 Mar;24 Suppl 1:S66-70.
28. Van Leeuwen MT, Zwerver J, Akker-Scheek I:Extracorporeal shockwave therapy for patellar tendinopathy:a review of the literature. Br J Sports Med 2009,43:163-168.
29. Johannes Zwerver, Evert Verhagen, Fred Hartgens, Inge van den Akker-Scheek, Ron L Diercks, Zwerver.The Topgame-study:effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy. Design of a randomised controlled trial Musculoskeletal Disorders. BMC Musculoskelet Disord.2010 Feb 8;11:28.
30. Smidt N, Assendelft W, Arola H. Effectiveness of physiotherapy for lateral epicondylitis:a systemic review. Ann Med.2003;35:51-62.
31. Jobe F, Ciccotti M. Lateral and medial epicondylitis of the elbow. J Am Acad Orthop Surg.1994;2:1-8.
32.32.C Gaujoux-Viala, M Dougados, and L Gossec, Efficacy and safety of steroid injections for shoulder and elbow tendonitis:a meta-analysis of randomised controlled trials, Ann Rheum Dis.2009 December; 68(12): 1843-1849.
33. Martin Clementson,Ingemar Lore'n (?)E Leif Dahlberg,Mats A strom. SClerosing injections in midportion Achilles tendinopathy:a retrospective study of 25 patients, Knee Surg Sports Traumatol Arthrosc (2008) 16:887-890
34. Lake JE, Ishikawa SN.conservative treatment of Achilles tendinopathy: emerging techniques. Foot Ankle Clin.2009 Dec;14(4):663-74.
35. collen A, Hanemaaijer R, Lupu F, Quax P, van Lent N, Grimbergen J, Peters E, Koolwijk P, van Hinsbergh V. Membrane-type maxtrix metelloproteinase mediated angiogenesis in a fibrin-collagen matrix. Blood.2003; 101: 1810-1817.
36.36.R Brown, J Orchard, M Kinchington, A Hooper, G Nalder Aprotinin in the management of Achilles tendinopathy:a randomised controlled trial. Br J Sports Med 2006; 40:275-279.
37. John OrchardAndrew Massey,Richard Brown,Ade'line Cardon-Dunbar, Jamie Hofmann,Successful Management of Tendinopathy With Injections of the MMP-inhibitor Aprotinin, Clin Orthop Relat Res (2008) 466:1625-1632
38. Dietrich W, Spath P, ZuhlSDorf M, et al. Anaphylactic reactions of aprotinin reexposure in cardiac surgery:relation to antiaprotinin immunoglobulin G and E antibodies. Anesthesiology.2001;95:64-71.
39. Orchard J, Massey A, Rimmer J, Hofman J, Brown R. Delay of 6 weeks between aprotinin injections for tendinopathy reduces risk of allergic reaction. J Sci Med Sport.2007:Aug 11 epub
40. Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ., Mesenchymal Stem Cells and Insulin-Like Growth Factor-Ⅰ Gene-Enhanced Mesenchymal Stem Cells Improve Structural Aspects of Healing in Equine Flexor Digitorum Superficialis Tendons J Orthop Res.2009 Oct;27(10):1392-8.
41. Wang XT, Liu PY, Tang JB. Tendon healing in vitro:Genetic modification of tenocytes with exogenous PDGF gene and promotion of collagen gene expression. J Hand Surg (Am) 2004;29(5):884-890.
42. Liu Q, Muruve DA. Molecular basis of the inflammatory response to adenovirus vectors. Gene Ther.2003 Jun; 10(11):935-40.
43. Kryger GS, Chong AK, costa M, Pham H, Bates SJ, Chang J. A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering. J Hand Surg Am.2007 May-Jun;32(5):597-605.
44. Juncosa-Melvin N, Boivin GP, Gooch C, Galloway MT, West JR, Dunn MG, Butler DL. The effect of autologous mesenchymal stem cells on the biomechanics and histology of gelcollagen sponge constructs used for rabbit patellar tendon repair.Tissue Eng.2006;12:369-379.
45. Soon MY, Hassan A, Hui JH, Goh JC, Lee EH. An analysis of soft tissue allograft anterior cruciate ligament reconstruction in a rabbit model:a short-term study of the use of mesenchymal stem cells to enhance tendon osteointegration. Am J Sports Med.2007;35:962-971.
46. Chong AK, Ang AD, Goh JC, Hui JH, Lim AY, Lee EH, Lim BH. Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model. J BoneJoint Surg Am.2007;89:74-81.
47. Lacitignola, Crovace. Rossi, Francioso,Cell therapy for tendinitis, experimental and Clinical report.Vet Res commun 2008; 32 (Suppll):S33-S38
48. ROGER K. W. SMITH, Mesenchymal stem cell therapy for equine tendinopathy.Disability and Rehabilitation,2008; 30(20-22):1752-1758.
49. Richardson LE, Dudhia J, Sadler CJ, Goodship AE, Smith RKW. Extracellular matrix cues for mesenchymal stem cell differentiation. Proceedings of the 53rd Orthopaedic Research Society 2007;32:472.
50. 聂继乎,温树正,细胞生长因子在肌腱修复中作用的研究进展.《医学综述》。2008年14卷1期：11-13页。
51. Anitua M, Sa'nchez E, Nurden A, Nurden P, Orive G, Andi'a I.New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol.2006; 24(5):227-34.
52. Brandon P. Donnelly, BS; Alan J. Nixon, BVSc, MS; Jennifer L. Haupt, BS; Linda A. Dahlgren,NuCleotide structure of equine platelet-derived growth factor-A and -B and expression in horses with induced acute tendinitis.Am J Vet Res.2006 Jul;67(7):1218-25.
53. Everts P, Knape J, Weirich G, Schonberger J, Hoffman J, Overdevest E. Platelet- rich plasma and platelet gel:a review. JECT.2006;38:174-87.
54. Rolf CG, Fu BS, Pau A, Wang W, Chan B.Increased cell proliferation and associated expression of PDGFRbeta causing hypercellularity in patellar tendinosis. Rheumatology Oxford.2001 Mar;40(3):256-61.
55. Ranly D, Lohmann C, Andreacchio D, Boyan B, Schwartz Z. Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in nude mice. J Bone Joint Surg.2007;89.
56. Sharma P, Maffulli N.,Tendinopathy and tendon injury:The future, Disability and Rehabilitation,2008; 30(20-22):1733-1745)139-46.
57. Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers.2006 Nov;10(4):515-27
58. Scott A, Lian 0, Bahr R, Hart DA, Duronio V., VEGF expression in patellar tendinopathy:a preliminary study. Clin Orthop Relat Res.2008 Jul;466(7): 598-604. Epub 2008 May 6.
59. Danielson P, Alfredson H, Forsgren S, Distribution of general (PGP 9.5) and sensory (substance P/CGRP) innervations in the human patellar tendon.Knee Surg Sports Traumatol Arthrosc.2006 Feb; 14(2):125-32. Epub 2005 Jun 28.
60.60.Antitua E, Andia I, Sanchez M, Azofra J, Del Mar Zalduendo M,De La Fuente M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF productions by human tendon cells in culture. J Orthop Res.2005;23:281-6.
61. 任强,黄昌林,郭振海,兔跟腱修复过程中胰岛素样生长因子-Ⅰ的表达,Journal of zhengzhou University(Medical Sciences)Nov.2005; Vol40 No.6
62. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med.2003; 33(5):381-94.
63. Banes AJ, Horesovsky G, Larson C, Tsuzaki M, Judex S,A rchambault J, et al. Mechanical load stimulates expression of novel genes in vivo and in vitro in avian flexor tendon cells.Osteoarth Cartilage 1999;7:141-153.
64. 宋德业,倪江东,体外培养肌腱细胞增殖与碱性成纤维细胞,医学临床研2007年8月第24卷第8期
65. Sheng J, Zeng B, Jiang P. Effects of exogenous basic fibroblast in-sheathed tendon healing and adhesion, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007 Jul;21(7):733-7.
66. Marx R, Garg A. Dental and craniofacial applications of plateletrich plasma.出版社：Quintessence Publishing company,出版日期：2005年1月
67. Everts P, Knape J, Weirich G, Schonberger J, Hoffman J,Overdevest E, et al. Platelet-rich plasma and platelet gel:a review. JECT.2006;38:174-87.
68. Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N.. Autologous platelet rich plasma for arthroscopic rotator cuff repair.:A pilot study. Disabil Rehabil. 2008; 30(20-22):1584-9.
69. 余情,陈统一,创伤后富血小板血浆治疗研究进展,国际骨科学杂志,2008年7月第29卷第4期
70. Allan Mishra, Padmaja Tummala, Aaron King, Byung Lee, Mark Kraus,Victor Tse, Christopher R.Jacobs, Buffered Platelet-Rich Plasma Enhances Mesenchymal Stem Cell Proliferation and Chondrogenic Differentiation. TISSUE ENGINEERING:Part C Volume 15, Number 00,2009
71. E. Anitua, M. Sanchez, M. M. Zalduendo, M. de la Fuente, R. Prado, G. Orive and I. Andia.Fibroblastic response to treatment with different preparations rich in growth factors. Cell Prolif.2009 Apr;42(2):162-70. Epub 2009 Feb 24.
72. Moon YL, Jo SH, Song CH, Park G, Lee HJ, Jang SJ.Autologous Bone Marrow Plasma Injection after Arthroscopic Debridementfor Elbow Tendinosis. Ann Acad Med Singapore.2008;Jul;37(7):559-63.
73. Gardner MJ, Demetrakopoulos D, Klepchick P, Mooar P. The efficacy of autologous platelet gel in pain control and blood loss in total knee arthroplasty:an analysis of the haemoglobin, narcotic requirement and range of motion. Int Orthop.2006;31:309-13.
74. Berghoff W, Pietrzak W, Rhodes R. Platelet-rich plasma applicationduring Closure following total knee arthroplasty.Orthopedics.2006;29(7):590-8.
75. Kajikawa Y, Morihara T, Sakamoto H, Matsuda K, Oshima Y,Yoshida A, et al. Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing. J Cell Physiol.2008;215(3):837-45.
76. Taylor M, Norman T, Clovis N, Blaha D. The response of rabbit patellar tendons after autologous blood injection. Med Sci Sports Exerc. 2002;34(1):70-3
77. de Vos RJ, van Veldhoven PL, Moen MH, Weir A, Tol JL, Maffulli N., Autologous growth factor injections in chronic tendinopathy:a systematic review. Br Med Bull.2010 Mar 2.
78. 陈琳,富含血小板血浆临床应用的优势,中国口腔种植学杂志2008年第13卷第3期
79. 张卫兵,洪光祥,康皓富。血小板血浆对兔骨髓间充质干细胞增殖的作用,中国组织工程研究与 1 临床康复第,12卷34期
1. Magnusson SP, Langberg H, Kjaer M. Nat Rev Rheumatol. The pathogenesis of tendinopathy:balancing the response to loading. Nat Rev Rheumatol.2010 May; 6(5):262-8. Epub 2010 Mar 23.
2. Sensebe L, Bourin P.Mesenchymal stem cells for therapeutic purposes. Transplantation.2009 May 15;87(9 Suppl):S49-53.
3. ROGER K. W. SMITH. Mesenchymal stem cell therapy for equine tendinopathy, Disability and Rehabilitation,2008; 30(20-22):1752-1758
4. Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ.Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons.J Orthop Res.2009 Oct; 27(10):1392-8.
5. Park JS, Hashi C, Li S.Culture of bone marrow mesenchymal stem cells on engineered matrix. Methods Mol Biol.2010;621:117-37.
6. Taralyn McCarrel, Lisa Fortier. Temporal Growth Factor Release from Platelet-Rich Plasma, Trehalose Lyophilized Platelets, and Bone Marrow Aspirate and Their Effect on Tendon and Ligament Gene Expression.Journal of orthopaedic research.2009 vol.27 no.8
7. Lacci KM, Dardik A. Platelet-rich plasma:support for its use in wound healing. Yale J Biol Med.2010 Mar;83(1):1-9.
8. Xiaobing CHENG,1 Delin LEI,1 Tianqiu MAO,1 Shuyong YANG.1 Fulin CHEN,2 Wei WU1 Repair of critical bone defects with injectable platelet rich plasma/bone marrow-derived stromal cells composite:experimental study in rabbits.Ulus Travma Acil Cerrahi Derg 2008;14(2):87-95
9. 黄谦吴涛金丹黄爱文江汕裴国献.不同比例激活富血小板血浆对其生长因子浓度及人骨髓基质干细胞增殖的影响.中华创伤骨科杂志2008年10月第10卷第10期
10.张卫兵,洪光祥,康皓富。血小板血浆对兔骨髓间充质干细胞增殖的作用,中国组织工程研究与 1 临床康复第,12卷34期
11. Wen-Fei Nia, Li-Hui Yinb,*, Jike Luc, Hua-Zi Xua, Yong-Long Chia, Jian-Bo Wub, Nu Zhangd In vitro neural differentiation of bone marrow stromal cells induced by cocultured olfactory ensheathing cells. Neurosci Lett.2010 Mar 27.
12. LI Zhuo, GU Tian-xiang and ZHANG Yu-hai. Hepatocyte growth factor Combined with insulin like growth factor-1 improves expression of GATA-4 in mesenchymal stem cells cocultured with cardiomyocytes Chin Med J 2008; 121(4):336-340
13. Richardson LE, Dudhia J, Sadler CJ, Goodship AE, Smith RKW. Extracellular matrix cues for mesenchymal stem cell differentiation. Proceedings of the 53rd OrthopaedicResearch Society 2007;32:472.
14. Magnusson SP, Langberg H, Kjaer M. The pathogenesis of tendinopathy: balancing the response to loading.Nat Rev Rheumatol.2010 May;6(5):262-8. Epub 2010 Mar 23
15. Sahoo S, Ang LT, Cho-Hong Goh J, Toh SL. Bioactive nanofibers for fibroblastic differentiation of mesenchymal precursor cells for ligament/tendon tissue engineering applications. Differentiation.2010 Feb;79(2):102-10. Epub 2009 Dec 5.
16.王锋,吴小涛,王运涛,李果,张明.非接触共培养条件下人BMSCs对氧化应激环境中退变髓核细胞凋亡的保护研究.中国修复重建外科杂志2010年4月第24卷第4期
17. P. Sharmal, N. Maffulli. Biology of tendon injury:healing, modeling and remodeling.L J Musculoskelet Neuronal Interact 2006; 6(2):181-190
18. Denitsa Docheva, Ernst B. Hunziker, Reinhard Fassler, Oliver Bandau. Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation. Molecular and cellular biology, Jan.2005, P699-705, Vol.25, No.2
19. Omae H, Zhao C, Sun YL, An KN, Amadio PC. Multilayer tendon slices seeded with bone marrow stromal cells:a novel composite for tendon engineering. J Orthop Res.2009 Jul;27(7):937-42.
20.许峰,刘伟,曹谊林.肌腱细胞的生物特性.《中华医学研究杂志》.2003年第3卷第11期
21.夏冰,王捷,郭立达,詹纯列,肖育华,杨传红.不同种属骨髓间充质干细胞体外培养特性的比较研究,中国微侵袭神经外科杂志2006年第11卷第12期：555-557