Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage

Stem Cell Research & Therapy

Ngoc Kim Phan³  Vien Tuong Le²  Thanh Duc Nguyen²  Triet Dinh Duong²  Dung Minh Le³  Nhan Lu-Chinh Phan³  Nhung Hai Truong³  Ngoc Bich Vu³  Dat Quoc Ngo¹  Khanh Hong-Thien Bui²  Phuc Van Pham³ 

[1] Department of Pathology, University of Medicine and Pharmacy, 217 Hong Bang, District 5, Ho Chi Minh City, Vietnam;University of Medical Center, Ho Chi Minh University of Medicine and Pharmacy, 215 Hong Bang, District 5, Ho Chi Minh City, Vietnam;Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, 227 Nguyen Van Cu, District 5, Ho Chi Minh City, Vietnam

关键词: Platelet-rich plasma;    Osteoarthritis;    Mesenchymal stem cells;    Joint failure;    Articular cartilage injury;    Adipose tissue-derived stem cells;   

Others  :  847157
DOI  :  10.1186/scrt277

 received in 2013-05-16, accepted in 2013-07-16,  发布年份 2013

【 摘 要 】

Introduction

Adipose-derived stem cells (ADSCs) have been isolated, expanded, and applied in the treatment of many diseases. ADSCs have also been used to treat injured articular cartilage. However, there is controversy regarding the treatment efficiency. We considered that ADSC transplantation with activated platelet-rich plasma (PRP) may improve injured articular cartilage compared with that of ADSC transplantation alone. In this study, we determined the role of PRP in ADSC transplantation to improve the treatment efficiency.

Methods

ADSCs were isolated and expanded from human adipose tissue. PRP was collected and activated from human peripheral blood. The effects of PRP were evaluated in vitro and in ADSC transplantation in vivo. In vitro, the effects of PRP on ADSC proliferation, differentiation into chondrogenic cells, and inhibition of angiogenic factors were investigated at three concentrations of PRP (10%, 15% and 20%). In vivo, ADSCs pretreated with or without PRP were transplanted into murine models of injured articular cartilage.

Results

PRP promoted ADSC proliferation and differentiation into chondrogenic cells that strongly expressed collagen II, Sox9 and aggrecan. Moreover, PRP inhibited expression of the angiogenic factor vascular endothelial growth factor. As a result, PRP-pretreated ADSCs improved healing of injured articular cartilage in murine models compared with that of untreated ADSCs.

Conclusion

Pretreatment of ADSCs with PRP is a simple method to efficiently apply ADSCs in cartilage regeneration. This study provides an important step toward the use of autologous ADSCs in the treatment of injured articular cartilage.

【 授权许可】

   
2013 Van Pham et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Borrione P, Gianfrancesco AD, Pereira MT, Pigozzi F: Platelet-rich plasma in muscle healing. Am J Phys Med Rehabil 2010, 89:854-861.
• [2]Yu W, Wang J, Yin J: Platelet-rich plasma: a promising product for treatment of peripheral nerve regeneration after nerve injury. Int J Neurosci 2011, 121:176-180.
• [3]Kim DH, Je YJ, Kim CD, Lee YH, Seo YJ, Lee JH, Lee Y: Can platelet-rich plasma be used for skin rejuvenation? Evaluation of effects of platelet-rich plasma on human dermal fibroblast. Ann Dermatol 2011, 23:424-431.
• [4]Cho JW, Kim SA, Lee KS: Platelet-rich plasma induces increased expression of G1 cell cycle regulators, type I collagen, and matrix metalloproteinase-1 in human skin fibroblasts. Int J Mol Med 2012, 29:32-36.
• [5]Kwon DR, Park GY, Lee SU: The effects of intra-articular platelet-rich plasma injection according to the severity of collagenase-induced knee osteoarthritis in a rabbit model. Ann Rehabil Med 2012, 36:458-465.
• [6]Lippross S, Moeller B, Haas H, Tohidnezhad M, Steubesand N, Wruck CJ, Kurz B, Seekamp A, Pufe T, Varoga D: Intraarticular injection of platelet-rich plasma reduces inflammation in a pig model of rheumatoid arthritis of the knee joint. Arthritis Rheum 2011, 63:3344-3353.
• [7]Siclari A, Mascaro G, Gentili C, Kaps C, Cancedda R, Boux E: Cartilage repair in the knee with subchondral drilling augmented with a platelet-rich plasma-immersed polymer-based implant. Knee Surg Sports Traumatol Arthrosc 2013. Epub ahead of print
• [8]Lee GW, Son JH, Kim JD, Jung GH: Is platelet-rich plasma able to enhance the results of arthroscopic microfracture in early osteoarthritis and cartilage lesion over 40 years of age? Eur J Orthop Surg Traumatol 2013, 23:581-587.
• [9]Jang SJ, Kim JD, Cha SS: Platelet-rich plasma (PRP) injections as an effective treatment for early osteoarthritis. Eur J Orthop Surg Traumatol 2013, 23:573-580.
• [10]Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A: Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med 2013, 41:356-364.
• [11]Spakova T, Rosocha J, Lacko M, Harvanova D, Gharaibeh A: Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil 2012, 91:411-417.
• [12]Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH: Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001, 7:211-228.
• [13]Zimmerlin L, Donnenberg VS, Rubin JP, Donnenberg AD: Mesenchymal markers on human adipose stem/progenitor cells. Cytometry A 2013, 83:134-140.
• [14]Zhu X, Du J, Liu G: The comparison of multilineage differentiation of bone marrow and adipose-derived mesenchymal stem cells. Clin Lab 2012, 58:897-903.
• [15]Gaiba S, Franca LP, Franca JP, Ferreira LM: Characterization of human adipose-derived stem cells. Acta Cir Bras 2012, 27:471-476.
• [16]Khan WS, Adesida AB, Tew SR, Longo UG, Hardingham TE: Fat pad-derived mesenchymal stem cells as a potential source for cell-based adipose tissue repair strategies. Cell Prolif 2012, 45:111-120.
• [17]Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statemen. Cytotherapy 2006, 8:315-317.
• [18]Christodoulou I, Kolisis FN, Papaevangeliou D, Zoumpourlis V: Comparative evaluation of human mesenchymal stem cells of fetal (Wharton’s jelly) and adult (adipose tissue) origin during prolonged in vitro expansion: considerations for cytotherapy. Stem Cells Int 2013, 2013:246134.
• [19]Harn HJ, Lin SZ, Hung SH, Subeq YM, Li YS, Syu WS, Ding DC, Lee RP, Hsieh DK, Lin PC, Chiou TW: Adipose-derived stem cells can abrogate chemical-induced liver fibrosis and facilitate recovery of liver function. Cell Transplant 2012, 21:2753-2764.
• [20]Gu JH, Ji YH, Dhong ES, Kim DH, Yoon ES: Transplantation of adipose derived stem cells for peripheral nerve regeneration in sciatic nerve defects of the rat. Curr Stem Cell Res Ther 2012, 7:347-355.
• [21]Liu G, Cheng Y, Guo S, Feng Y, Li Q, Jia H, Wang Y, Tong L, Tong X: Transplantation of adipose-derived stem cells for peripheral nerve repair. Int J Mol Med 2011, 28:565-572.
• [22]Santiago LY, Clavijo-Alvarez J, Brayfield C, Rubin JP, Marra KG: Delivery of adipose-derived precursor cells for peripheral nerve repair. Cell Transplant 2009, 18:145-158.
• [23]Mazo M, Hernández S, Gavira JJ, Abizanda G, Araña M, López-Martínez T, Moreno C, Merino J, Martino-Rodríguez A, Uixeira A, García de Jalón JA, Pastrana J, Martínez-Caro D, Prósper F: Treatment of reperfused ischemia with adipose-derived stem cells in a preclinical Swine model of myocardial infarction. Cell Transplant 2012, 21:2723-2733.
• [24]Rigol M, Solanes N, Farré J, Roura S, Roqué M, Berruezo A, Bellera N, Novensà L, Tamborero D, Prat-Vidal C, Huzman MA, Batlle M, Hoefsloot M, Sitges M, Ramírez J, Dantas AP, Merino A, Sanz G, Brugada J, Bayés-Genís A, Heras M: Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration. J Card Fail 2010, 16:357-366.
• [25]Pecanha R, Bagno LL, Ribeiro MB, Robottom Ferreira AB, Moraes MO, Zapata-Sudo G, Kasai-Brunswick TH, Campos-de-Carvalho AC, Goldenberg RC, Saar Werneck-de-Castro JP: Adipose-derived stem-cell treatment of skeletal muscle injury. J Bone Joint Surg Am 2012, 94:609-617.
• [26]Xiao J, Zhang C, Zhang Y, Zhang X, Zhao J, Liang J, Zhong X, Chen Y: Transplantation of adipose-derived mesenchymal stem cells into a murine model of passive chronic immune thrombocytopenia. Transfusion 2012, 52:2551-2558.
• [27]Yang JJ, Yang X, Liu ZQ, Hu SY, Du ZY, Feng LL, Liu JF, Chen YD: Transplantation of adipose tissue-derived stem cells overexpressing heme oxygenase-1 improves functions and remodeling of infarcted myocardium in rabbits. Tohoku J Exp Med 2012, 226:231-241.
• [28]Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F, Alfaro M, Rodriguez JP, Harman RJ, Patel AN, Murphy MP, Lee RR, Minev B: Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med 2009, 7:29. BioMed Central Full Text
• [29]Scuderi N, Ceccarelli S, Onesti MG, Fioramonti P, Guidi C, Romano F, Frati L, Angeloni A, Marchese C: Human adipose-derived stem cells for cell-based therapies in the treatment of systemic sclerosis. Cell Transplant 2013, 22:779-795.
• [30]Black LL, Gaynor J, Adams C, Dhupa S, Sams AE, Taylor R, Harman S, Gingerich DA, Harman R: Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Vet Ther 2008, 9:192-200.
• [31]Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, Gingerich DA, Harman R: Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther 2007, 8:272-284.
• [32]Guercio A, Di Marco P, Casella S, Cannella V, Russotto L, Purpari G, Di Bella S, Piccione G: Production of canine mesenchymal stem cells from adipose tissue and their application in dogs with chronic osteoarthritis of the humeroradial joints. Cell Biol Int 2012, 36:189-194.
• [33]Toghraie FS, Chenari N, Gholipour MA, Faghih Z, Torabinejad S, Dehghani S, Ghaderi A: Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in rabbit. Knee 2011, 18:71-75.
• [34]Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW: Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res 2009, 27:1675-1680.
• [35]Lee JM, Im GI: SOX trio-co-transduced adipose stem cells in fibrin gel to enhance cartilage repair and delay the progression of osteoarthritis in the rat. Biomaterials 2012, 33:2016-2024.
• [36]ter Huurne MC, van Lent PLEM, Blom AB, Blattes R, Jeanson Y, Casteilla L, Jorgensen C: A single injection of adipose-derived stem cells protects against cartilage damage and lowers synovial activation in experimental osteoarthritis. Arthritis Rheum 2011, 63:1784.
• [37]ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, Jeanson J, Noël D, Casteilla L, Jorgensen C, van den Berg W, van Lent PL: Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 2012, 64:3604-3613.
• [38]Van Pham P, Hong-Thien Bui K, Quoc Ngo D, Tan Khuat L, Kim Phan N: Transplantation of nonexpanded adipose stromal vascular fraction and platelet-rich plasma for articular cartilage injury treatment in mice model. J Med Eng 2013, 2013:7.
• [39]Murphy JM, Fink DJ, Hunziker EB, Barry FP: Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 2003, 48:3464-3474.
• [40]Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W, Tuan RS, Zhang C: Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 2012, 33:7008-7018.
• [41]Pak J: Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep 2011, 5:296. BioMed Central Full Text
• [42]Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, Choi YJ: Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 2013, 29:748-755.
• [43]Lee CS, Burnsed OA, Raghuram V, Kalisvaart J, Boyan BD, Schwartz Z: Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration. Stem Cell Res Ther 2012, 3:35. BioMed Central Full Text
• [44]Phuc PV, Nhung TH, Loan DT, Chung DC, Ngoc PK: Differentiating of banked human umbilical cord blood-derived mesenchymal stem cells into insulin-secreting cells. In Vitro Cell Dev Biol Anim 2011, 47:54-63.
• [45]Martin I, Jakob M, Schafer D, Dick W, Spagnoli G, Heberer M: Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints. Osteoarthr Cartil 2001, 9:112-118.
• [46]Li Y, Tew SR, Russell AM, Gonzalez KR, Hardingham TE, Hawkins RE: Transduction of passaged human articular chondrocytes with adenoviral, retroviral, and lentiviral vectors and the effects of enhanced expression of SOX9. Tissue Eng 2004, 10:575-584.
• [47]Van Pham P, Dang LT-T, Truong NH, Phan NK: Can activated platelet rich plasma combined with adipose-derived stem cells be used to treat skin wrinkles? a mechanism study. In Medical Advancements in Aging and Regenerative Technologies: Clinical Tools and Applications. Germany: IGI Global; 2013:313-329.
• [48]Gharibi B, Hughes FJ: Effects of medium supplements on proliferation, differentiation potential, and in vitro expansion of mesenchymal stem cells. Stem Cells Transl Med 2012, 1:771-782.
• [49]Chieregato K, Castegnaro S, Madeo D, Astori G, Pegoraro M, Rodeghiero F: Epidermal growth factor, basic fibroblast growth factor and platelet-derived growth factor-bb can substitute for fetal bovine serum and compete with human platelet-rich plasma in the ex vivo expansion of mesenchymal stromal cells derived from adipose tissue. Cytotherapy 2011, 13:933-943.
• [50]Kocaoemer A, Kern S, Kluter H, Bieback K: Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue. Stem Cells 2007, 25:1270-1278.
• [51]Zhang YS, He JH, Xiao GY, Li QM: Effect of platelet-rich plasma on the proliferation and adipogenic differentiation of human adipose-derived stem cells in vitro. Nan Fang Yi Ke Da Xue Xue Bao 2011, 31:525-528.
• [52]Li H, Liu D, Yu Y, Wu T: Experimental research of the promotion effect of autogeneic PRP on osteogenic differentiation of human adipose-derived stem cells in vitro. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2009, 23:732-736.
• [53]Kakudo N, Minakata T, Mitsui T, Kushida S, Notodihardjo FZ, Kusumoto K: Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts. Plast Reconstr Surg 2008, 122:1352-1360.
• [54]Pfander D, Kortje D, Zimmermann R, Weseloh G, Kirsch T, Gesslein M, Cramer T, Swoboda B: Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints. Ann Rheum Dis 2001, 60:1070-1073.
• [55]Enomoto H, Inoki I, Komiya K, Shiomi T, Ikeda E, Obata K, Matsumoto H, Toyama Y, Okada Y: Vascular endothelial growth factor isoforms and their receptors are expressed in human osteoarthritic cartilage. Am J Pathol 2003, 162:171-181.
• [56]Pufe T, Harde V, Petersen W, Goldring MB, Tillmann B, Mentlein R: Vascular endothelial growth factor (VEGF) induces matrix metalloproteinase expression in immortalized chondrocytes. J Pathol 2004, 202:367-374.
• [57]Mifune Y, Matsumoto T, Takayama K, Ota S, Li H, Meszaros LB, Usas A, Nagamune K, Gharaibeh B, Fu FH, Huard J: The effect of platelet-rich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthr Cartil 2013, 21:175-185.
• [58]Browning SR, Weiser AM, Woolf N, Golish SR, SanGiovanni TP, Scuderi GJ, Carballo C, Hanna LS: Platelet-rich plasma increases matrix metalloproteinases in cultures of human synovial fibroblasts. J Bone Joint Surg Am 2012, 94:e1721-e1727.
• [59]Cheng T, Yang C, Weber N, Kim HT, Kuo AC: Fibroblast growth factor 2 enhances the kinetics of mesenchymal stem cell chondrogenesis. Biochem Biophys Res Commun 2012, 426:544-550.
• [60]Kabiri A, Esfandiari E, Hashemibeni B, Kazemi M, Mardani M, Esmaeili A: Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture. Biochem Biophys Res Commun 2012, 424:234-238.
• [61]Buckley CT, Kelly DJ: Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs. J Mech Behav Biomed Mater 2012, 11:102-111.
• [62]Stewart AA, Byron CR, Pondenis H, Stewart MC: Effect of fibroblast growth factor-2 on equine mesenchymal stem cell monolayer expansion and chondrogenesis. Am J Vet Res 2007, 68:941-945.
• [63]Bhang SH, Jeon JY, La WG, Seong JY, Hwang JW, Ryu SE, Kim BS: Enhanced chondrogenic marker expression of human mesenchymal stem cells by interaction with both TGF-β3 and hyaluronic acid. Biotechnol Appl Biochem 2011, 58:271-276.
• [64]Fan H, Zhang C, Li J, Bi L, Qin L, Wu H, Hu Y: Gelatin microspheres containing TGF-beta3 enhance the chondrogenesis of mesenchymal stem cells in modified pellet culture. Biomacromolecules 2008, 9:927-934.
• [65]Koh YG, Choi YJ: Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee 2012, 19:902-907.