Skip to main content
Erschienen in: International Orthopaedics 6/2016

14.07.2015 | Original Paper

Study design: in vitro and in vivo assessment of bone morphogenic protein 2 combined with platelet-rich plasma on treatment of disc degeneration

verfasst von: Yang Hou, Guodong Shi, Jiangang Shi, Guohua Xu, Yongfei Guo, Peng Xu

Erschienen in: International Orthopaedics | Ausgabe 6/2016

Einloggen, um Zugang zu erhalten

Abstract

Objective

Our aim was to investigate the biological effects of bone morphogenic protein 2 (BMP2) on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocyte-like cells in platelet-rich plasma (PRP) gel in vitro. In addition, the effectiveness of BMP2-transduced BMSCs in combined with PRP gel to repair the degenerated intervertebral disc in a rabbit model was also evaluated.

Summary of background data

Previous studies have shown that tissue engineering provides many promising advantages to treating disc degeneration and may reverse the pathological process of disc degeneration.

Methods

The expressions of types I, II and X collagen, aggrecan and Sox9 of the BMP2-transduced BMSCs in monolayer or PRP gel were examined by reverse transcriptase polymerase chain reaction (RT-PCR). Sixty New Zealand white rabbits were divided into five groups: 12 normal controls; 12 puncture operated with only disc degeneration being induced; 12 PRP transplantation animals; 12 BMSC and PRP-transplantation animals; 12 BMP2-transduced BMSCs and PRP-transplantation animals. The effect of BMP2-transduced BMSCs on degenerated discs were evaluated by magnetic resonance image (MRI) scan, histology, immunohistochemistry and Western blot analysis.

Results

BMP2 could facilitate chondrogenic differentiation of BMSCs in monolayer or PRP gel. The discs treated with BMP2-transduced BMSCs exhibited relatively well-preserved nucleus pulposus (NP) structure. Significantly higher T2-weighted signal intensity and a greater amount of extracellular matrix were observed in the BMP2-transduced BMSC group compared with other groups. In addition, the presences of BMP2-transduced BMSCs were identified at week 12 postoperatively in vivo.

Conclusions

BMP2-transduced BMSCs can maintain the chondrocyte-like phenotype in PRP gel in vitro, and the combined use of these two agents can significantly promote repair of the degenerated discs in vivo.
Literatur
1.
Zurück zum Zitat Yang H, Wu J, Liu J, Ebraheim M, Castillo S, Liu X et al (2010) Transplanted mesenchymal stem cells with pure fibrinous gelatin-transforming growth factor-beta1 decrease rabbit intervertebral disc degeneration. Spine J 10:802–810CrossRefPubMed Yang H, Wu J, Liu J, Ebraheim M, Castillo S, Liu X et al (2010) Transplanted mesenchymal stem cells with pure fibrinous gelatin-transforming growth factor-beta1 decrease rabbit intervertebral disc degeneration. Spine J 10:802–810CrossRefPubMed
2.
Zurück zum Zitat Leung VY, Chan D, Cheung KM (2006) Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J 15:S406–S413CrossRefPubMed Leung VY, Chan D, Cheung KM (2006) Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J 15:S406–S413CrossRefPubMed
3.
Zurück zum Zitat Risbud MV, Shapiro IM, Vaccaro AR, Albert TJ (2004) Stem cell regeneration of the nucleus pulposus. Spine J 4:348S–353SCrossRefPubMed Risbud MV, Shapiro IM, Vaccaro AR, Albert TJ (2004) Stem cell regeneration of the nucleus pulposus. Spine J 4:348S–353SCrossRefPubMed
4.
Zurück zum Zitat Pearce R, Grimmer B, Adams M (1987) Degeneration and the chemical composition of the human intervertebral disc. J Orthop Res 5:198–205CrossRefPubMed Pearce R, Grimmer B, Adams M (1987) Degeneration and the chemical composition of the human intervertebral disc. J Orthop Res 5:198–205CrossRefPubMed
5.
Zurück zum Zitat Walsh AJ, Bradford DS, Lotz JC (2004) In vivo growth fator treatment of degenerated intervertebral discs. Spine 29:156–163CrossRefPubMed Walsh AJ, Bradford DS, Lotz JC (2004) In vivo growth fator treatment of degenerated intervertebral discs. Spine 29:156–163CrossRefPubMed
6.
Zurück zum Zitat Masuda K, Oegema TR Jr, An HS (2004) Growth factors and treatment of intervertebral disc degeneration. Spine 29:2757–2769CrossRefPubMed Masuda K, Oegema TR Jr, An HS (2004) Growth factors and treatment of intervertebral disc degeneration. Spine 29:2757–2769CrossRefPubMed
7.
Zurück zum Zitat Li J, Kim KS, Park JS, Elmer WA, Hutton WC, Yoon ST (2003) BMP-2 and CDMP-2: stimulation of chondrocyte production of proteoglycan. J Orthop Sci 8:829–835CrossRefPubMed Li J, Kim KS, Park JS, Elmer WA, Hutton WC, Yoon ST (2003) BMP-2 and CDMP-2: stimulation of chondrocyte production of proteoglycan. J Orthop Sci 8:829–835CrossRefPubMed
8.
Zurück zum Zitat Li J, Yoon T, Hutton W (2004) Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech 17:423–428CrossRefPubMed Li J, Yoon T, Hutton W (2004) Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech 17:423–428CrossRefPubMed
9.
Zurück zum Zitat Chen WH, Lo WC, Lee JJ, Su CH, Lin CT, Liu HY et al (2006) Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in platelet-rich plasma. J Cell Physiol 209:744–754CrossRefPubMed Chen WH, Lo WC, Lee JJ, Su CH, Lin CT, Liu HY et al (2006) Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in platelet-rich plasma. J Cell Physiol 209:744–754CrossRefPubMed
10.
Zurück zum Zitat Liu Y, Kalen A, Risto O, Wahlstrom O (2002) Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen 10:336–340CrossRefPubMed Liu Y, Kalen A, Risto O, Wahlstrom O (2002) Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen 10:336–340CrossRefPubMed
11.
Zurück zum Zitat Lucarelli E, Beccheroni A, Donati D, Sangiorgi L, Cenacchi A, Del Vento AM et al (2003) Platelet-derived growth factors enhance proliferation of human stromal stem cells. Biomaterials 24:3095–3100CrossRefPubMed Lucarelli E, Beccheroni A, Donati D, Sangiorgi L, Cenacchi A, Del Vento AM et al (2003) Platelet-derived growth factors enhance proliferation of human stromal stem cells. Biomaterials 24:3095–3100CrossRefPubMed
12.
Zurück zum Zitat Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K et al (2003) Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 24:3531–3541CrossRefPubMed Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K et al (2003) Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 24:3531–3541CrossRefPubMed
13.
Zurück zum Zitat Yang HN, Park JS, Na K, Woo DG, Kwon YD, Park KH (2009) The use of greenfluorescence gene (GFP)-modified rabbit mesenchymal stem cells (rMSCs) cocultured with chondrocytes in hydrogel constructs to reveal the chondrogenesis of MSCs. Biomaterials 30:6374–6385CrossRefPubMed Yang HN, Park JS, Na K, Woo DG, Kwon YD, Park KH (2009) The use of greenfluorescence gene (GFP)-modified rabbit mesenchymal stem cells (rMSCs) cocultured with chondrocytes in hydrogel constructs to reveal the chondrogenesis of MSCs. Biomaterials 30:6374–6385CrossRefPubMed
14.
Zurück zum Zitat Elliott D, Yerramalli C, Beckstein J, Boxberger JI, Johannessen W, Vresilovic EJ (2008) The effect of relative needle diameter in puncture and sham injection animal models of degeneration. Spine 33:588–596CrossRefPubMed Elliott D, Yerramalli C, Beckstein J, Boxberger JI, Johannessen W, Vresilovic EJ (2008) The effect of relative needle diameter in puncture and sham injection animal models of degeneration. Spine 33:588–596CrossRefPubMed
15.
Zurück zum Zitat Huang YC, Yang ZM, Chen XH, Tan MY, Wang J, Li XQ et al (2009) Isolation of mesenchymal stem cells from human placental decidua basalis and resistance to hypoxia and serum deprivation. Stem Cell Rev 5:247–255CrossRefPubMed Huang YC, Yang ZM, Chen XH, Tan MY, Wang J, Li XQ et al (2009) Isolation of mesenchymal stem cells from human placental decidua basalis and resistance to hypoxia and serum deprivation. Stem Cell Rev 5:247–255CrossRefPubMed
16.
Zurück zum Zitat Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M et al (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27:335–345CrossRefPubMed Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M et al (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27:335–345CrossRefPubMed
17.
18.
Zurück zum Zitat Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884CrossRefPubMed Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884CrossRefPubMed
19.
Zurück zum Zitat Wang SZ, Chang Q, Lu J, Wang C (2015) Growth factors and platelet-rich plasma: promising biological strategies for early intervertebral disc degeneration. Int Orthop 39:927–934CrossRefPubMed Wang SZ, Chang Q, Lu J, Wang C (2015) Growth factors and platelet-rich plasma: promising biological strategies for early intervertebral disc degeneration. Int Orthop 39:927–934CrossRefPubMed
20.
Zurück zum Zitat Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT et al (2010) Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 31:3572–3579CrossRefPubMed Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT et al (2010) Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 31:3572–3579CrossRefPubMed
21.
Zurück zum Zitat Anitua E, Sanchez M, Orive G, Andia I (2007) The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials 28:4551–4560CrossRefPubMed Anitua E, Sanchez M, Orive G, Andia I (2007) The potential impact of the preparation rich in growth factors (PRGF) in different medical fields. Biomaterials 28:4551–4560CrossRefPubMed
22.
Zurück zum Zitat Chen WH, Liu HY, Lo WC, Wu SC, Chi CH, Chang HY et al (2009) Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 30:5523–5533CrossRefPubMed Chen WH, Liu HY, Lo WC, Wu SC, Chi CH, Chang HY et al (2009) Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 30:5523–5533CrossRefPubMed
23.
Zurück zum Zitat Wang SZ, Rui YF, Tan Q et al (2013) Enhancing intervertebral disc repair and regeneration through biology: platelet-rich plasma as an alternative strategy. Arthritis Res Ther 15:220CrossRefPubMedPubMedCentral Wang SZ, Rui YF, Tan Q et al (2013) Enhancing intervertebral disc repair and regeneration through biology: platelet-rich plasma as an alternative strategy. Arthritis Res Ther 15:220CrossRefPubMedPubMedCentral
Metadaten
Titel
Study design: in vitro and in vivo assessment of bone morphogenic protein 2 combined with platelet-rich plasma on treatment of disc degeneration
verfasst von
Yang Hou
Guodong Shi
Jiangang Shi
Guohua Xu
Yongfei Guo
Peng Xu
Publikationsdatum
14.07.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
International Orthopaedics / Ausgabe 6/2016
Print ISSN: 0341-2695
Elektronische ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-015-2840-5

Weitere Artikel der Ausgabe 6/2016

International Orthopaedics 6/2016 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.