Top

Journal of Orthopaedic Surgery and Research

Published in:

Open Access 01-12-2016 | Research article

Characterization of progenitor cells derived from torn human rotator cuff tendons by gene expression patterns of chondrogenesis, osteogenesis, and adipogenesis

Authors: Issei Nagura, Takeshi Kokubu, Yutaka Mifune, Atsuyuki Inui, Fumiaki Takase, Yasuhiro Ueda, Takeshi Kataoka, Masahiro Kurosaka

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2016

Abstract

Background

It is important to regenerate the tendon-to-bone interface after rotator cuff repair to prevent re-tears. The cells from torn human rotator cuff were targeted, and their capacity for multilineage differentiation was investigated.

Methods

The edges of the rotator cuff were harvested during arthroscopic rotator cuff repair from nine patients, minced into pieces, and cultured on dishes. Adherent cells were cultured, phenotypically characterized. Then expandability, differentiation potential and gene expression were analyzed.

Results

Flow cytometry revealed that the mesenchymal stem cells (MSC)-related markers CD29, CD44, CD105, and CD166 were positive. However, CD14, CD34, and CD45 were negative. On RT-PCR analyses, the cells showed osteogenic, adipogenic, and chondrogenic potential after 3 weeks of culture under the respective differentiation conditions. In addition, SOX9, type II collagen, and type X collagen expression patterns during chondrogenesis were similar to those of endochondral ossification at the enthesis.

Conclusions

The cells derived from torn human rotator cuff are multipotent mesenchymal stem cells with the ability to undergo multilineage differentiation, suggesting that MSCs form this tissue could be regenerative capacity for potential self-repair.

Kasten P, Keil C, Grieser T, Raiss P, Streich N, Loew M. Prospective randomized comparison of arthroscopic versus mini-open rotator cuff repair of the supraspinatus tendon. Int Orthop. 2011;35:1663–70.CrossRefPubMedPubMedCentral

Gerber C, Fuchs B, Hodler J. The results of repair of massive tears of t0068e rotator cuff. J Bone Joint Surg Am. 2000;82:505–15.PubMed

Lafosse L, Brozska R, Toussaint B, Gobezie R. The outcome and structural integrity of arthroscopic rotator cuff repair with use of the double-row suture anchor technique. J Bone Joint Surg Am. 2007;89:1533–41.CrossRefPubMed

Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am. 2004;86:219–24.PubMed

Newsham-West R, Nicholson H, Walton M, Milburn P. Long-term of a healing bone-tendon interface: a histological observation in the sheep model. J Anat. 2007;210:318–27.CrossRefPubMedPubMedCentral

Harryman 2nd DT, Mack LA, Wang KY, Jaskins SE, Richardson ML, Matsen 3rd FA. Repairs of the rotator cuff: correlation of functional results with integrity of the cuff. J Bone Joint Surg Am. 1991;73:982–89.PubMed

Liu SH, Baker CL. Arthroscopically assisted rotator cuff repair: correlation of functional results with integrity of the cuff. Arthroscopy. 1994;10:54–60.CrossRefPubMed

St Pierre P, Olson EJ, Elliott JJ, O’Hair KC, McKinney LA, Ryan J. Tendon-healing to cortical bone compared with healing to a cancellous trough. A biomechanical and histological evaluation in gouts. J Bone Joint Surg Am. 1995;77:1858–66.PubMed

Bedi A, Kawamura S, Ying L, Rodeo SA. Differences in tendon graft healing between the intra-articular and extra-articular ends of the bone tunnel. HSS J. 2009;5:51–7.CrossRefPubMedPubMedCentral

10.

Funakoshi T, Martin S, Spector M. Distribution of lubricin in the ruptured human rotator cuff and biceps tendon. Clin Orthop Relat Res. 2010;468:1588–99.CrossRefPubMedPubMedCentral

11.

Sun Y, Berger EJ, Zhao C, Jay GD, An KN, Amadio PC. Expression and mapping of lubricin in canine flexor tendon. J Orthop Res. 2006;24:1861–68.CrossRefPubMed

12.

Rodeo SA. Biologic augmentation of rotator cuff tendon repair. J Shoulder Elbow Surg. 2007;16:191–7.CrossRef

13.

Gulotta LV, Kovacevic D, Ehteshami JR, Dagher E, Packer JD, Rodeo SA. Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model. Am J Sports Med. 2009;37:2126–33.CrossRefPubMed

14.

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;284:143–7.CrossRefPubMed

15.

Ehninger A, Trumpp A. The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med. 2011;208:421–8.CrossRefPubMedPubMedCentral

16.

Paulty S, Klatte F, Strobel C, Schmidmaier G, Greiner S, Scheibel M, Wildermann B. Characterization of tendon cell cultures of the human rotator cuff. European Cells and Materials. 2010;20:84–97.

17.

Randelli P, Conforti E, Piccoli M, Ragone V, Creo P, Cirillo F, Masuzzo P, Tringali C, Cabitza P, Tettamanti G, Gangliano N, Anastasia L. Isolation and characterization of 2 new human rotator cuff and long head of biceps tendon cells possessing stem cell-like renewal and multipotential differentiation capacity. Am J Sports Med. 2013;41:1653–64.CrossRefPubMed

18.

Tsai CC, Huang TF, Ma HL, Chiang ER, Hung SC. Isolation of mesenchymal stem cells form shoulder rotator cuff: a potential source for muscle and tendon repair. Cell Transplant. 2013;22:413–22.CrossRefPubMed

19.

Utsunomiya H, Uchida S, Sekiya I, Sakai A, Moridera K, Nakamura T. Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears. Am J Sports Med. 2013;41:657–68.CrossRefPubMed

20.

Benjamin M, Evans EJ, Copp L. The histology of tendon attachment to bone in man. J Anat. 1986;149:89–100.PubMedPubMedCentral

21.

Cristofalo VJ, Allen RG, Pingnolo RJ, Martin BG, Beck JC. Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc Natl Acad Sci U S A. 1998;95:10614–19.CrossRefPubMedPubMedCentral

22.

Aslan H, Zilberman Y, Kandel L, Liebergall M, Oskouian RJ, Gazit D, Gazit Z. Osteogenic differentiation of noncultured immunoisolated bone marrow-derived CD105+ cells. Stem Cells. 2006;24:1728–37.CrossRefPubMed

23.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Dean R, Keating A, Prockop D, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.CrossRefPubMed

24.

Gumina S, Di Giorgio G, Bertino A, Della Rocca C, Sardella B, Postacchini F. Inflammatory infiltrate of the edges of a torn rotator cuff. Int Orthop. 2006;30:371–4.CrossRefPubMedPubMedCentral

25.

Nourissat G, Diop A, Maurel N, Salvat C, Dumont S, Pigenet A, Gosset M, Houard X, Berenbaum F. Mesenchymal stem cell therapy regenerates the native bone-tendon junction after surgical repair in a degenerative rat model. PLoS One. 2010;18:e12248.CrossRef

26.

Manning CN, Kim HM, Sakiyama-Elbert S, Galatz LM, Havliglu N, Thomopoulos S. Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model. J Orthop Res. 2011;29:1099–105.CrossRefPubMed

27.

Oliva F, Barisani D, Grasso A, Maffulli N. Gene expression analysis in calcific tendinopathy of the rotator cuff. Eur Cell Mater. 2011;20:548–57.

28.

Sekiya I, David C, Darwin J. BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells. Biochem Biophys Res Commun. 2001;284:411–8.CrossRefPubMed

29.

Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet. 1999;22:85–9.CrossRefPubMed

30.

Lefebvre V, Huang W, Harley VR, Goodfellow PN, de Crombrugghe B. SOX9 is a potent activator of the chondrocyte-specific enhancer of pro alpha 1 (II) collagen gene. Mol Cell Biol. 1997;17:2336–46.CrossRefPubMedPubMedCentral

31.

Zhao Q, Eberspaecher H, Lefebvre V, de Crombrugghe B. Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis. Dey Dyn. 1997;209:377–86.CrossRef

32.

Thomopoulos S, Hattersley G, Rosen V, Mertens M, Galatz L, Williams GR, Soslowsky LJ. The localized expression of extracellular matrix components in healing tendon insertion sites: an in situ hybridization study. J Orthop Res. 2002;20:454–63.CrossRefPubMed

33.

Fujioka H, Thakur R, Wang GJ, Mizuno K, Balian G, Hurwitz SR. Comparison of surgically attached and nonattached repair of the rat Achilles tendon-bone interface. Cellular organization and type X collagen expression. Connect Tissue Res. 1998;37:205–18.CrossRefPubMed

34.

Galatz L, Rothermich S, VanderPloeg K, Peterson B, Sandell L, Thomopoulos S. Development of the supraspinatus tendon-to-bone insertion: localized expression of extracellular matrix and growth factor genes. J Orthop Res. 2007;25:1621–8.CrossRefPubMed

Title: Characterization of progenitor cells derived from torn human rotator cuff tendons by gene expression patterns of chondrogenesis, osteogenesis, and adipogenesis
Authors: Issei Nagura
Takeshi Kokubu
Yutaka Mifune
Atsuyuki Inui
Fumiaki Takase
Yasuhiro Ueda
Takeshi Kataoka
Masahiro Kurosaka
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2016
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-016-0373-2

At a glance: The STEP trials

Springer Medicine

Characterization of progenitor cells derived from torn human rotator cuff tendons by gene expression patterns of chondrogenesis, osteogenesis, and adipogenesis

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Identification of molecular pathway changes after spinal cord injury by microarray analysis

Validation of the FASH (Functional Assessment Scale for Acute Hamstring Injuries) questionnaire for German-speaking football players

Load distribution between cephalic screws in a dual lag screw trochanteric nail

Erratum to: Comparison of radiological spino-pelvic sagittal parameters in skiers and non-athletes

Reducing surgical levels by paraspinal mapping and diffusion tensor imaging techniques in lumbar spinal stenosis

The effect of screw thread length on initial stability of Schatzker type 1 tibial plateau fracture fixation: a biomechanical study