Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc.
Intervertebral disc (IVD) degeneration, a common cause of low back pain in humans, is a relentlessly progressive phenomenon with no currently available effective treatment. In an attempt to solve this dilemma, we transplanted autologous mesenchymal stem cells (MSCs) from bone marrow into a rabbit model of disc degeneration to determine if stem cells could repair degenerated IVDs. LacZ expressing MSCs were transplanted to rabbit L2-L3, L3-L4 and L4-L5 IVDs 2 weeks after induction of degeneration. Changes in disc height by plain radiograph, T2-weighted signal intensity in magnetic resonance imaging (MRI), histology, immunohistochemistry and matrix associated gene expressions were evaluated between normal controls (NC) without operations, sham operated with only disc degeneration being induced, and MSC-transplanted animals for a 24-week period. Results showed that after 24 weeks post-MSC transplantation, degenerated discs of MSC-transplanted group animals regained a disc height value of about 91%, MRI signal intensity of about 81%, compared to NC group discs. On the other hand, sham-operated group discs demonstrated the disc height value of about 67% and MRI signal intensity of about 60%. Macroscopic and histological evaluations confirmed relatively preserved nucleus with circular annulus structure in MSC-transplanted discs compared to indistinct structure seen in sham. Restoration of proteoglycan accumulation in MSC-transplanted discs was suggested from immunohistochemistry and gene expression analysis. These data indicate that transplantation of MSCs effectively led to regeneration of IVDs in a rabbit model of disc degeneration as suggested in our previous pilot study. MSCs may serve as a valuable resource in cell transplantation therapy for degenerative disc disease.
Sakai
Daisuke
D
Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. daisakai@is.icc.u-tokai.ac.jp
Mochida
Joji
J
Iwashina
Toru
T
Hiyama
Akihiko
A
Omi
Hiroko
H
Imai
Masaaki
M
Nakai
Tomoko
T
Ando
Kiyoshi
K
Hotta
Tomomitsu
T
D053674:Aggrecans; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D003094:Collagen / Q000627:therapeutic use*; D024043:Collagen Type II / Q000235:genetics; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005697:Galactosides / Q000032:analysis; D015870:Gene Expression / Q000235:genetics; D007211:Indoles / Q000032:analysis; D007403:Intervertebral Disc / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D007763:Lac Operon / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics; D011817:Rabbits; D011859:Radiography; D044968:Regenerative Medicine / Q000379:methods*; D013122:Spinal Diseases / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D053675:Versicans
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D005697:Galactosides; D007211:Indoles; D037181:Lectins, C-Type; D011509:Proteoglycans; C059821:atelocollagen; D053675:Versicans; D003094:Collagen; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside