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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Abstract
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
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Kuroda, R | | | | Usas, A | | | | Kubo, S | | | | Corsi, K | | | | Peng, H | | | | Rose, T | | | | Cummins, J | | | | Fu, FH | ffu@pitt.edu | FFU | | Huard, J | | | |
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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 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/21677 |
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