Evidence for skeletal progenitor cells in the degenerate human intervertebral disc.
METHODS
To identify and characterize endogenous progenitor cell population from intervertebral disc.


OBJECTIVE
To determine if progenitor cells exist in degenerate human discs.


BACKGROUND
Back pain, a significant source of morbidity in our society, is directly linked to the pathology of the intervertebral disc. Because disc disease is accompanied by a loss of cellularity, there is considerable interest in regeneration of cells of both the anulus fibrosus (AF) and nucleus pulposus (NP).


METHODS
To determine if skeletal progenitor cells are present in the disc, samples were obtained from the degenerate AF and NP of 5 patients (Thompson grade 2 and 3, mean age 34 +/- 7.6 years) undergoing anterior cervical discectomy and fusion procedures as well as adult rat lumbar spine.


RESULTS
Cells isolated from degenerate human tissues expressed CD105, CD166, CD63, CD49a, CD90, CD73, p75 low affinity nerve growth factor receptor, and CD133/1, proteins that are characteristic of marrow mesenchymal stem cells. In osteogenic media, there was an induction of alkaline phosphatase activity and expression of alkaline phosphatase, osteocalcin, and Runx-2 mRNA. When maintained in adipogenic media, a small percentage of cells displayed evidence of adipogenic differentiation: accumulation of cytosolic lipid droplets and increased expression of peroxisome proliferator-activated receptor-gamma2 and lipoprotein lipase mRNA. AF- and NP-derived cells also evidenced chondrogenic differentiation. CD133 (+) cells in the AF were able to commit to either the chondrogenic or adipogenic lineages. The results of the human disc studies were confirmed using cell derived from the NP and AF tissue of the mature rat disc.


CONCLUSIONS
The analytical data indicated that the pathologically degenerate human disc contained populations of skeletal progenitor cells. These findings suggest that these endogenous progenitors may be used to orchestrate the repair of the intervertebral disc.
Risbud
Makarand V
MV
Department of Orthopaedic Surgery and Graduate Program in Tissue Engineering and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. makarand.risbud@jefferson.edu
Guttapalli
Asha
A
Tsai
Tsung-Ting
TT
Lee
Joon Y
JY
Danielson
Keith G
KG
Vaccaro
Alexander R
AR
Albert
Todd J
TJ
Gazit
Zulma
Z
Gazit
Dan
D
Shapiro
Irving M
IM
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000328:Adult; D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002574:Cervical Vertebrae / Q000473:pathology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007403:Intervertebral Disc / Q000473:pathology*; D008055:Lipids / Q000032:analysis; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics; D008159:Lumbar Vertebrae / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D013122:Spinal Diseases / Q000473:pathology*
D015703:Antigens, CD; D050659:Core Binding Factor Alpha 1 Subunit; D008055:Lipids; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D047495:PPAR gamma; C493709:RUNX2 protein, human; D017475:Receptors, Nerve Growth Factor; D015675:Osteocalcin; D008071:Lipoprotein Lipase; D000469:Alkaline Phosphatase