Transplantation of mesenchymal stem cells in a canine disc degeneration model.
Transplantation of mesenchymal stem cells (MSCs) is effective in decelerating disc degeneration in small animals; much remains unknown about this new therapy in larger animals or humans. Fas-ligand (FasL), which is only found in tissues with isolated immune privilege, is expressed in IVDs, particularly in the nucleus pulposus (NP). Maintaining the FasL level is important for IVD function. This study evaluated whether MSC transplantation has an effect on the suppression of disc degeneration and preservation of immune privilege in a canine model of disc degeneration. Mature beagles were separated into a normal control group (NC), a MSC group, and the disc degeneration (nucleotomy-only) group. In the MSC group, 4 weeks after nucleotomy, MSCs were transplanted into the degeneration-induced discs. The animals were followed for 12 weeks after the initial operation. Subsequently, radiological, histological, biochemical, immunohistochemical, and RT-PCR analyses were performed. MSC transplantation effectively led to the regeneration of degenerated discs. FACS and RT-PCR analyses of MSCs before transplantation demonstrated that the MSCs expressed FasL at the genetic level, not at the protein level. GFP-positive MSCs detected in the NP region 8 weeks after transplantation expressed FasL protein. The results of this study suggest that MSC transplantation may contribute to the maintenance of IVD immune privilege by the differentiation of transplanted MSCs into cells expressing FasL.
Hiyama
Akihiko
A
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, 259-1193, Japan.
Mochida
Joji
J
Iwashina
Toru
T
Omi
Hiroko
H
Watanabe
Takuya
T
Serigano
Kenji
K
Tamura
Futoshi
F
Sakai
Daisuke
D
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D004285:Dogs; D053222:Fas Ligand Protein / Q000378:metabolism*; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000502:physiology*; D007632:Keratan Sulfate / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013122:Spinal Diseases / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; D012333:RNA, Messenger; D019014:fas Receptor; D007632:Keratan Sulfate