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Published in: Journal of Translational Medicine 1/2014

Open Access 01-12-2014 | Research

Efficacy of a mesenchymal stem cell loaded surgical mesh for tendon repair in rats

Authors: Lew C Schon, Nicholas Gill, Margaret Thorpe, Joel Davis, Joshua Nadaud, Jooyoung Kim, Jeremy Molligan, Zijun Zhang

Published in: Journal of Translational Medicine | Issue 1/2014

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Abstract

Objectives

The purpose of this study was to investigate the efficacy of a composite surgical mesh for delivery of mesenchymal stem cells (MSCs) in tendon repair.

Methods

The MSC-loaded mesh composed of a piece of conventional surgical mesh and a layer of scaffold, which supported MSC-embedded alginate gel. A 3-mm defect was surgically created at the Achilles tendon-gastrocnemius/soleus junction in 30 rats. The tendon defects were repaired with either 1) MSC-loaded mesh; or 2) surgical mesh only; or 3) routine surgical suture. Repaired tendons were harvested at days 6 and 14 for histology, which was scored on the bases of collagen organization, vascularity and cellularity, and immunohistochemisty of types I and III collagen.

Results

In comparison with the other two repair types, at day 6, the MSC-loaded mesh significantly improved the quality of the repaired tendons with dense and parallel collagen bundles, reduced vascularity and increased type I collagen. At day 14, the MSC-loaded mesh repaired tendons had better collagen formation and organization.

Conclusion

The MSC-loaded mesh enhanced early tendon healing, particularly the quality of collagen bundles. Application of the MSC-loaded mesh, as a new device and MSC delivery vehicle, may benefit to early functional recovery of the ruptured tendon.
Appendix
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Literature
1.
go back to reference James R, Kesturu G, Balian G, Chhabra AB: Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am. 2008, 33 (1): 102-112. 10.1016/j.jhsa.2007.09.007.CrossRefPubMed James R, Kesturu G, Balian G, Chhabra AB: Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. J Hand Surg Am. 2008, 33 (1): 102-112. 10.1016/j.jhsa.2007.09.007.CrossRefPubMed
2.
go back to reference Sharma P, Maffulli N: Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am. 2005, 87 (1): 187-202. 10.2106/JBJS.D.01850.CrossRefPubMed Sharma P, Maffulli N: Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am. 2005, 87 (1): 187-202. 10.2106/JBJS.D.01850.CrossRefPubMed
3.
go back to reference Lui PP, Rui YF, Ni M, Chan KM: Tenogenic differentiation of stem cells for tendon repair-what is the current evidence?. J Tissue Eng Regen Med. 2011, 5 (8): e144-e163. 10.1002/term.424.CrossRefPubMed Lui PP, Rui YF, Ni M, Chan KM: Tenogenic differentiation of stem cells for tendon repair-what is the current evidence?. J Tissue Eng Regen Med. 2011, 5 (8): e144-e163. 10.1002/term.424.CrossRefPubMed
4.
go back to reference Butler DL, Juncosa-Melvin N, Boivin GP, Galloway MT, Shearn JT, Gooch C, Awad H: Functional tissue engineering for tendon repair: A multidisciplinary strategy using mesenchymal stem cells, bioscaffolds, and mechanical stimulation. J Orthop Res. 2008, 26 (1): 1-9. 10.1002/jor.20456.CrossRefPubMed Butler DL, Juncosa-Melvin N, Boivin GP, Galloway MT, Shearn JT, Gooch C, Awad H: Functional tissue engineering for tendon repair: A multidisciplinary strategy using mesenchymal stem cells, bioscaffolds, and mechanical stimulation. J Orthop Res. 2008, 26 (1): 1-9. 10.1002/jor.20456.CrossRefPubMed
5.
go back to reference Kuschner SH, Orlando CA, McKellop HA, Sarmiento A: A comparison of the healing properties of rabbit Achilles tendon injuries at different levels. Clin Orthop Relat Res. 1991, 272: 268-273.PubMed Kuschner SH, Orlando CA, McKellop HA, Sarmiento A: A comparison of the healing properties of rabbit Achilles tendon injuries at different levels. Clin Orthop Relat Res. 1991, 272: 268-273.PubMed
6.
go back to reference Chiodo CP, Wilson MG: Current concepts review: acute ruptures of the achilles tendon. Foot Ankle Int. 2006, 27 (4): 305-313.PubMed Chiodo CP, Wilson MG: Current concepts review: acute ruptures of the achilles tendon. Foot Ankle Int. 2006, 27 (4): 305-313.PubMed
7.
go back to reference Józsa L, Kvist M, Bálint BJ, Reffy A, Järvinen M, Lehto M, Barzo M: The role of recreational sport activity in Achilles tendon rupture. A clinical, pathoanatomical, and sociological study of 292 cases. Am J Sports Med. 1989, 17 (3): 338-343. 10.1177/036354658901700305.CrossRefPubMed Józsa L, Kvist M, Bálint BJ, Reffy A, Järvinen M, Lehto M, Barzo M: The role of recreational sport activity in Achilles tendon rupture. A clinical, pathoanatomical, and sociological study of 292 cases. Am J Sports Med. 1989, 17 (3): 338-343. 10.1177/036354658901700305.CrossRefPubMed
8.
go back to reference Cao Y, Liu Y, Liu W, Shan Q, Buonocore SD, Cui L: Bridging tendon defects using autologous tenocyte engineered tendon in a hen model. Plast Reconstr Surg. 2002, 110 (5): 1280-1289. 10.1097/00006534-200210000-00011.CrossRefPubMed Cao Y, Liu Y, Liu W, Shan Q, Buonocore SD, Cui L: Bridging tendon defects using autologous tenocyte engineered tendon in a hen model. Plast Reconstr Surg. 2002, 110 (5): 1280-1289. 10.1097/00006534-200210000-00011.CrossRefPubMed
9.
go back to reference Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 1999, 284 (5411): 143-147. 10.1126/science.284.5411.143.CrossRefPubMed Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 1999, 284 (5411): 143-147. 10.1126/science.284.5411.143.CrossRefPubMed
10.
go back to reference Caplan AI, Dennis JE: Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006, 98 (5): 1076-1084. 10.1002/jcb.20886.CrossRefPubMed Caplan AI, Dennis JE: Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006, 98 (5): 1076-1084. 10.1002/jcb.20886.CrossRefPubMed
11.
go back to reference Lee JY, Zhou Z, Taub PJ, Ramcharan M, Li Y, Akinbiyi T, Maharam ER, Leong DJ, Laudier DM, Ruike T, Torina PJ, Zaidi M, Majeska RJ, Schaffler MB, Flatow EL, Sun HB: BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo. PLoS One. 2011, 6 (3): e17531-10.1371/journal.pone.0017531.PubMedCentralCrossRefPubMed Lee JY, Zhou Z, Taub PJ, Ramcharan M, Li Y, Akinbiyi T, Maharam ER, Leong DJ, Laudier DM, Ruike T, Torina PJ, Zaidi M, Majeska RJ, Schaffler MB, Flatow EL, Sun HB: BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo. PLoS One. 2011, 6 (3): e17531-10.1371/journal.pone.0017531.PubMedCentralCrossRefPubMed
12.
go back to reference Hoffmann A, Pelled G, Turgeman G, Eberle P, Zilberman Y, Shinar H, Keinan-Adamsky K, Winkel A, Shahab S, Navon G, Gross G, Gazit D: Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. J Clin Invest. 2006, 116 (4): 940-952. 10.1172/JCI22689.PubMedCentralCrossRefPubMed Hoffmann A, Pelled G, Turgeman G, Eberle P, Zilberman Y, Shinar H, Keinan-Adamsky K, Winkel A, Shahab S, Navon G, Gross G, Gazit D: Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells. J Clin Invest. 2006, 116 (4): 940-952. 10.1172/JCI22689.PubMedCentralCrossRefPubMed
13.
go back to reference Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P: Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12. BMC Cell Biol. 2009, 10: 29-10.1186/1471-2121-10-29.PubMedCentralCrossRefPubMed Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P: Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12. BMC Cell Biol. 2009, 10: 29-10.1186/1471-2121-10-29.PubMedCentralCrossRefPubMed
14.
go back to reference Mazzocca AD, McCarthy MB, Chowaniec D, Cote MP, Judson CH, Apostolakos J, Solovyova O, Beitzel K, Arciero RA: Bone marrow-derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin. Arthroscopy. 2011, 27 (11): 1459-1471. 10.1016/j.arthro.2011.06.029.CrossRefPubMed Mazzocca AD, McCarthy MB, Chowaniec D, Cote MP, Judson CH, Apostolakos J, Solovyova O, Beitzel K, Arciero RA: Bone marrow-derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin. Arthroscopy. 2011, 27 (11): 1459-1471. 10.1016/j.arthro.2011.06.029.CrossRefPubMed
15.
go back to reference Yin Z, Chen X, Chen JL, Shen WL, Hieu Nguyen TM, Gao L, Ouyang HW: The regulation of tendon stem cell differentiation by the alignment of nanofibers. Biomaterials. 2010, 31 (8): 2163-2175. 10.1016/j.biomaterials.2009.11.083.CrossRefPubMed Yin Z, Chen X, Chen JL, Shen WL, Hieu Nguyen TM, Gao L, Ouyang HW: The regulation of tendon stem cell differentiation by the alignment of nanofibers. Biomaterials. 2010, 31 (8): 2163-2175. 10.1016/j.biomaterials.2009.11.083.CrossRefPubMed
16.
go back to reference Wang QW, Chen ZL, Piao YJ: Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein (BMP) 12 gene transfer. J Biosci Bioeng. 2005, 100 (4): 418-422. 10.1263/jbb.100.418.CrossRefPubMed Wang QW, Chen ZL, Piao YJ: Mesenchymal stem cells differentiate into tenocytes by bone morphogenetic protein (BMP) 12 gene transfer. J Biosci Bioeng. 2005, 100 (4): 418-422. 10.1263/jbb.100.418.CrossRefPubMed
17.
go back to reference Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK: Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet J. 2012, 44 (1): 25-32. 10.1111/j.2042-3306.2011.00363.x.CrossRefPubMed Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK: Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet J. 2012, 44 (1): 25-32. 10.1111/j.2042-3306.2011.00363.x.CrossRefPubMed
18.
go back to reference 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, 27 (10): 1392-1398. 10.1002/jor.20887.CrossRefPubMed 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, 27 (10): 1392-1398. 10.1002/jor.20887.CrossRefPubMed
19.
go back to reference 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 gel-collagen sponge constructs used for rabbit patellar tendon repair. Tissue Eng. 2006, 12 (2): 369-379. 10.1089/ten.2006.12.369.CrossRefPubMed 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 gel-collagen sponge constructs used for rabbit patellar tendon repair. Tissue Eng. 2006, 12 (2): 369-379. 10.1089/ten.2006.12.369.CrossRefPubMed
20.
go back to reference Awad HA, Butler DL, Boivin GP, Smith FN, Malaviya P, Huibregtse B, Caplan AI: Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng. 1999, 5 (3): 267-277. 10.1089/ten.1999.5.267.CrossRefPubMed Awad HA, Butler DL, Boivin GP, Smith FN, Malaviya P, Huibregtse B, Caplan AI: Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng. 1999, 5 (3): 267-277. 10.1089/ten.1999.5.267.CrossRefPubMed
21.
go back to reference Riley GP, Goddard MJ, Hazleman BL: Histopathological assessment and pathological significance of matrix degeneration in supraspinatus tendons. Rheumatology (Oxford). 2001, 40 (2): 229-230. 10.1093/rheumatology/40.2.229.CrossRef Riley GP, Goddard MJ, Hazleman BL: Histopathological assessment and pathological significance of matrix degeneration in supraspinatus tendons. Rheumatology (Oxford). 2001, 40 (2): 229-230. 10.1093/rheumatology/40.2.229.CrossRef
22.
go back to reference Aström M, Rausing A: Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings. Clin Orthop Relat Res. 1995, 316: 151-164.PubMed Aström M, Rausing A: Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings. Clin Orthop Relat Res. 1995, 316: 151-164.PubMed
23.
go back to reference Qiu Y, Lim JJ, Scott L, Adams RC, Bui HT, Temenoff JS: PEG-based hydrogels with tunable degradation characteristics to control delivery of marrow stromal cells for tendon overuse injuries. Acta Biomater. 2011, 7 (3): 959-966. 10.1016/j.actbio.2010.11.002.CrossRefPubMed Qiu Y, Lim JJ, Scott L, Adams RC, Bui HT, Temenoff JS: PEG-based hydrogels with tunable degradation characteristics to control delivery of marrow stromal cells for tendon overuse injuries. Acta Biomater. 2011, 7 (3): 959-966. 10.1016/j.actbio.2010.11.002.CrossRefPubMed
24.
go back to reference Zhang ZJ, Huckle J, Francomano CA, Spencer RG: The effects of pulsed low-intensity ultrasound on chondrocyte viability, proliferation, gene expression and matrix production. Ultrasound Med Biol. 2003, 29 (11): 1645-1651. 10.1016/j.ultrasmedbio.2003.08.011.CrossRefPubMed Zhang ZJ, Huckle J, Francomano CA, Spencer RG: The effects of pulsed low-intensity ultrasound on chondrocyte viability, proliferation, gene expression and matrix production. Ultrasound Med Biol. 2003, 29 (11): 1645-1651. 10.1016/j.ultrasmedbio.2003.08.011.CrossRefPubMed
25.
go back to reference Aspenberg P: Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review. Int Orthop. 2007, 31 (6): 783-789. 10.1007/s00264-007-0398-6.PubMedCentralCrossRefPubMed Aspenberg P: Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review. Int Orthop. 2007, 31 (6): 783-789. 10.1007/s00264-007-0398-6.PubMedCentralCrossRefPubMed
26.
go back to reference Kuo CK, Tuan RS: Mechanoactive tenogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A. 2008, 14 (10): 1615-1627. 10.1089/ten.tea.2006.0415.CrossRefPubMed Kuo CK, Tuan RS: Mechanoactive tenogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A. 2008, 14 (10): 1615-1627. 10.1089/ten.tea.2006.0415.CrossRefPubMed
27.
go back to reference Chen YJ, Huang CH, Lee IC, Lee YT, Chen MH, Young TH: Effects of cyclic mechanical stretching on the mRNA expression of tendon/ligament-related and osteoblast-specific genes in human mesenchymal stem cells. Connect Tissue Res. 2008, 49 (1): 7-14. 10.1080/03008200701818561.CrossRefPubMed Chen YJ, Huang CH, Lee IC, Lee YT, Chen MH, Young TH: Effects of cyclic mechanical stretching on the mRNA expression of tendon/ligament-related and osteoblast-specific genes in human mesenchymal stem cells. Connect Tissue Res. 2008, 49 (1): 7-14. 10.1080/03008200701818561.CrossRefPubMed
28.
go back to reference Okamoto N, Kushida T, Oe K, Umeda M, Ikehara S, Iida H: Treating Achilles tendon rupture in rats with bone-marrow-cell transplantation therapy. J Bone Joint Surg Am. 2010, 92 (17): 2776-2784. 10.2106/JBJS.I.01325.CrossRefPubMed Okamoto N, Kushida T, Oe K, Umeda M, Ikehara S, Iida H: Treating Achilles tendon rupture in rats with bone-marrow-cell transplantation therapy. J Bone Joint Surg Am. 2010, 92 (17): 2776-2784. 10.2106/JBJS.I.01325.CrossRefPubMed
29.
go back to reference Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF: Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med. 2007, 13 (10): 1219-1227. 10.1038/nm1630.CrossRefPubMed Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF: Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med. 2007, 13 (10): 1219-1227. 10.1038/nm1630.CrossRefPubMed
30.
go back to reference Luo Q, Song G, Song Y, Xu B, Qin J, Shi Y: Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells. Cytotechnology. 2009, 61 (1–2): 1-10.PubMedCentralCrossRefPubMed Luo Q, Song G, Song Y, Xu B, Qin J, Shi Y: Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells. Cytotechnology. 2009, 61 (1–2): 1-10.PubMedCentralCrossRefPubMed
31.
go back to reference Tong WY, Shen W, Yeung CW, Zhao Y, Cheng SH, Chu PK, Chan D, Chan GC, Cheung KM, Yeung KW, Lam YW: Functional replication of the tendon tissue microenvironment by a bioimprinted substrate and the support of tenocytic differentiation of mesenchymal stem cells. Biomaterials. 2012, 33 (31): 7686-7698. 10.1016/j.biomaterials.2012.07.002.CrossRefPubMed Tong WY, Shen W, Yeung CW, Zhao Y, Cheng SH, Chu PK, Chan D, Chan GC, Cheung KM, Yeung KW, Lam YW: Functional replication of the tendon tissue microenvironment by a bioimprinted substrate and the support of tenocytic differentiation of mesenchymal stem cells. Biomaterials. 2012, 33 (31): 7686-7698. 10.1016/j.biomaterials.2012.07.002.CrossRefPubMed
32.
go back to reference Schulze-Tanzil G, Al-Sadi O, Wiegand E, Ertel W, Busch C, Kohl B, Pufe T: The role of pro-inflammatory and immunoregulatory cytokines in tendon healing and rupture: new insights. Scand J Med Sci Sports. 2011, 21 (3): 337-351. 10.1111/j.1600-0838.2010.01265.x.CrossRefPubMed Schulze-Tanzil G, Al-Sadi O, Wiegand E, Ertel W, Busch C, Kohl B, Pufe T: The role of pro-inflammatory and immunoregulatory cytokines in tendon healing and rupture: new insights. Scand J Med Sci Sports. 2011, 21 (3): 337-351. 10.1111/j.1600-0838.2010.01265.x.CrossRefPubMed
33.
go back to reference Butler DL, Juncosa N, Dressler MR: Functional efficacy of tendon repair processes. Annu Rev Biomed Eng. 2004, 6: 303-329. 10.1146/annurev.bioeng.6.040803.140240.CrossRefPubMed Butler DL, Juncosa N, Dressler MR: Functional efficacy of tendon repair processes. Annu Rev Biomed Eng. 2004, 6: 303-329. 10.1146/annurev.bioeng.6.040803.140240.CrossRefPubMed
34.
go back to reference Berglund M, Reno C, Hart DA, Wiig M: Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath. J Hand Surg Am. 2006, 31 (8): 1279-1287. 10.1016/j.jhsa.2006.06.011.CrossRefPubMed Berglund M, Reno C, Hart DA, Wiig M: Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath. J Hand Surg Am. 2006, 31 (8): 1279-1287. 10.1016/j.jhsa.2006.06.011.CrossRefPubMed
35.
go back to reference Williams IF, Heaton A, McCullagh KG: Cell morphology and collagen types in equine tendon scar. Res Vet Sci. 1980, 28 (3): 302-310.PubMed Williams IF, Heaton A, McCullagh KG: Cell morphology and collagen types in equine tendon scar. Res Vet Sci. 1980, 28 (3): 302-310.PubMed
Metadata
Title
Efficacy of a mesenchymal stem cell loaded surgical mesh for tendon repair in rats
Authors
Lew C Schon
Nicholas Gill
Margaret Thorpe
Joel Davis
Joshua Nadaud
Jooyoung Kim
Jeremy Molligan
Zijun Zhang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-12-110

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