Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears.
BACKGROUND
Recent studies report a relatively high failure rate for tendon-bone healing after rotator cuff repair. Several studies have investigated biologically augmented rotator cuff repair; however, none has shown the application of synovial mesenchymal stem cells for such repair.


OBJECTIVE
To demonstrate whether cells derived from shoulder tissues have mesenchymal stem cell properties and to identify which tissue is the best source of the mesenchymal stem cells.


METHODS
Controlled laboratory study.


METHODS
Forty-two patients with a diagnosed rotator cuff tear preoperatively were enrolled in this study. Human mesenchymal tissues were obtained during arthroscopic surgery for rotator cuff tears from 19 donors who met the inclusion criteria and had investigable amounts of tissue. Colony-forming units, yield obtained, expandability, differentiation potential, epitope profile, and gene expression were compared among the cells from 4 shoulder tissues: synovium of the glenohumeral joint, subacromial bursa, margin of the ruptured supraspinatus tendon, and residual tendon stump on the greater tuberosity (enthesis).


RESULTS
The number of live passage 0 cells from whole tissue was significantly higher in cells derived from the subacromial bursa (P < .05). Subacromial bursa-derived cells retained their expandability even at passage 10. In adipogenesis experiments, the frequency of Oil Red O-positive colonies was significantly higher for synovium- and subacromial bursa-derived cells than for tendon- and enthesis-derived cells (P < .0001). In studies of osteogenesis, the rate of von Kossa- and alkaline phosphatase-positive colonies was highest in subacromial bursa-derived cells (P < .0001). The chondrogenic potential was highest in cells derived from the enthesis. For epitope profiling, 11 surface antigens were measured, and most had similar epitope profiles, irrespective of cell source.


CONCLUSIONS
The findings indicate that the subacromial bursa is a good candidate for the source of mesenchymal stem cells in rotator cuff tears.


CONCLUSIONS
Synovial cells from the subacromial bursa in patients with rotator cuff tears are a superior cell source in vitro, suggesting that mesenchymal stem cells from this tissue could be good candidates for biological augmentation of rotator cuff repair.
Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan. utsu@med.uoeh-u.ac.jp
Hajime
H
Utsunomiya
Soshi
S
Uchida
Ichiro
I
Sekiya
Akinori
A
Sakai
Kuniaki
K
Moridera
Toshitaka
T
Nakamura
D050156:Adipogenesis; D001182:Arthroscopy; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000378:metabolism; D020219:Chondrogenesis; D003114:Colony-Forming Units Assay; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism; D000939:Epitopes; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis; D017006:Rotator Cuff / Q000601:surgery; D000070636:Rotator Cuff Injuries; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D012785:Shoulder Joint / Q000166:cytology* / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism; D013710:Tendons / Q000166:cytology* / Q000378:metabolism
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019002:CD56 Antigen; C499706:CXCL2 protein, human; D002135:Calcium-Binding Proteins; D054426:Chemokine CXCL2; D017630:Connexins; D000939:Epitopes; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C522918:NCAM1 protein, human; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D000072099:Serrate-Jagged Proteins; D000072259:Connexin 26; D007334:Insulin-Like Growth Factor I