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Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells

Kuroda, R and Usas, A and Kubo, S and Corsi, K and Peng, H and Rose, T and Cummins, J and Fu, FH and Huard, J (2006) Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis and Rheumatism, 54 (2). 433 - 442. ISSN 0004-3591

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Objective. Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle exhibit long-time proliferation, high self-renewal, and multipotent differentiation. This study was undertaken to investigate the ability of MDSCs that were retrovirally transduced to express bone morphogenetic protein 4 (BMP-4) to differentiate into chondrocytes in vitro and in vivo and enhance articular cartilage repair. Methods. Using monolayer and micromass pellet culture systems, we evaluated the in vitro chondrogenic differentiation of LacZ- and BMP-4-transduced MDSCs with or without transforming growth factor β1 (TGFβ1) stimulation. We used a nude rat model of a full-thickness articular cartilage defect to assess the duration of LacZ transgene expression and evaluate the ability of transplanted cells to acquire a chondrocytic phenotype. We evaluated cartilage repair macroscopically and histologically 4, 8, 12, and 24 weeks after surgery, and performed histologic grading of the repaired tissues. Results. BMP-4-expressing MDSCs acquired a chondrocytic plienotype in vitro more effectively than did MDSCs expressing only LacZ; the addition of TGFβ1 did not alter chondrogenic differentiation of the BMP-4-transduced MDSCs. LacZ expression within the repaired tissue continued for up to 12 weeks. Four weeks after surgery, we detected donor cells that coexpressed β-galactosidase and type II collagen, Histologic scoring of the defect sites 24 weeks after transplantation revealed significantly better cartilage repair in animals that received BMP-4-transduced MDSCs than in those that received MDSCs expressing only LacZ. Conclusion. Local delivery of BMP-4 toy genetically engineered MDSCs enhanced chondrogenesis and significantly improved articular cartilage repair in rats. © 2006, American College of Rheumatology.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kuroda, R
Usas, A
Kubo, S
Corsi, K
Peng, H
Rose, T
Cummins, J
Fu, FHffu@pitt.eduFFU
Huard, J
Date: 1 February 2006
Date Type: Publication
Journal or Publication Title: Arthritis and Rheumatism
Volume: 54
Number: 2
Page Range: 433 - 442
DOI or Unique Handle: 10.1002/art.21632
Schools and Programs: School of Medicine > Orthopaedic Surgery
Refereed: Yes
ISSN: 0004-3591
MeSH Headings: Animals; Biological Markers--metabolism; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins--genetics; Bone Morphogenetic Proteins--metabolism; Bone Morphogenetic Proteins--pharmacology; Cartilage, Articular--growth & development; Cartilage, Articular--injuries; Cartilage, Articular--pathology; Cell Differentiation; Chondrocytes--cytology; Chondrocytes--metabolism; Chondrogenesis--physiology; Collagen Type II--metabolism; Genetic Therapy; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells--cytology; Mesenchymal Stromal Cells--metabolism; Muscle, Skeletal--cytology; Muscle, Skeletal--metabolism; Proteoglycans--metabolism; Rats; Rats, Nude; Regeneration--physiology; Transduction, Genetic--methods; beta-Galactosidase--genetics; beta-Galactosidase--metabolism
PubMed ID: 16447218
Date Deposited: 09 Jun 2014 14:51
Last Modified: 04 Feb 2019 15:56


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