Recombinant growth/differentiation factor-5 (GDF-5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic

✍ Scribed by Shimaoka, Hideki ;Dohi, Yoshiko ;Ohgushi, Hajime ;Ikeuchi, Masako ;Okamoto, Masanori ;Kudo, Akira ;Kirita, Tadaaki ;Yonemasu, Kunio

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 330 KB
• Volume: 68A
• Category: Article
• ISSN: 0021-9304
• DOI: 10.1002/jbm.a.20059

✦ Synopsis

Abstract

To evaluate the growth/differentiation factor‐5 (GDF‐5) in the in vivo osteogenic potential of bone marrow mesenchymal stem cells (MSCs), we subcutaneously implanted five different kinds of hydroxyapatite (HA) ceramic implants: HA alone, GDF‐5/HA composites (GDF/HA), MSCs/HA composites, the MSCs/HA composites supplemented with GDF‐5 (GDF/MSCs/HA), and recombinant bone morphogenetic protein‐2 (BMP/MSCs/HA). Neither the HA alone nor the GDF/HA composites exhibited any bone formation at any time after implantation. At 4 weeks, the MSCs/HA composites exhibited a certain amount of bone formation in some pore areas. In contrast, at 2 weeks, the GDF/MSCs/HA composites exhibited histologically obvious de novo bone formation together with active osteoblasts in many pore areas and additional bone formation at 4 weeks. In the de novo formed bone, neither chondrocytes nor endochondral bone was detected. The GDF/MSCs/HA composites also showed high alkaline phosphatase (ALP) and osteocalcin expression determined at both the protein and gene levels and the high level of expression was well maintained even at 4 weeks. Compared with GDF/MSCs/HA, the BMP/MSCs/HA composites exhibited excellent osteogenesis with relatively early osteoblastic phenotype expression. The results indicate that GDF‐5 synergistically enhances de novo bone formation capability of MSCs/HA composite and suggest that tissue‐engineered GDF/MSCs/HA composites could be used as bone graft substitutes. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 168–176, 2004