Effects of Transplantation of hTIMP-1-Expressing Bone Marrow Mesenchymal Stem Cells on the Extracellular Matrix of Degenerative Intervertebral Discs in an In Vivo Rabbit Model.
METHODS
Prospective, randomized, and controlled animal study.


OBJECTIVE
To observe extracellular matrix (ECM) changes in degenerative intervertebral disc (IVD) after transplantation of bone marrow mesenchymal stem cells (BMSCs) virally transfected with a construct expressing "human tissue inhibitor of metalloproteinase 1" (hTIMP-1), and to discuss the feasibility of using this approach to treat IVD degeneration.


BACKGROUND
Intervertebral disc (IVD) degeneration is characterized by decreased cell numbers, bioactivity of the nucleus pulposus, and remodeled ECM. Exogenous genes can be targeted into cells to produce inhibition of ECM degradation and increase ECM content in IVDs, and thereby potentially stop or reverse degenerative processes and modify disc structure.


METHODS
BMSCs were isolated from a pure New Zealand white rabbit and identified by flow cytometry. Transgenic BMSCs were acquired by transfection with a recombinant adenovirus vector carrying the hTIMP-1 gene. Animal models of IVD degeneration were established by annulus puncture and then given intra-nucleus pulposus injections according to their random assignment into 3 groups: (1) a transgenic BMSC transplantation (TgBT) group that received BMSCs transfected with an hTIMP-1-expressing adenovirus vector; (2) a BMSC transplantation (BT) group that received unaltered BMSCs; and (3) a control group that received cell-free phosphate-buffered saline. Degree of degeneration was evaluated 12 weeks after modeling. ECM content was quantified using immunohistochemistry and spectrophotography. Expression of hTIMP-1 was observed via quantitative polymerase chain reaction, western blot, and immunohistochemistry.


RESULTS
Significantly fewer degenerative changes and increased ECM content were observed in the TBT and BT groups than the control group animals (P < 0.05). The TBT group had greater ECM content than did the BT group (P < 0.05), as well as higher levels of hTIMP-1 mRNA and protein.


CONCLUSIONS
Transplantation of BMSCs transfected with hTIMP-1 can increase ECM content by inhibiting ECM degradation and promoting ECM synthesis.


METHODS
N/A.
Department of Orthopedics, The First Affiliated Hospital, China Medical University, Shenyang, China.|Department of Orthopedics, The Second Affiliated Hospital, Shenyang Medical College, Shenyang, China.
Zhou
Z
Yi
Department of Orthopedics, The First Affiliated Hospital, China Medical University, Shenyang, China.
Tu
T
Guanjun
Department of Orthopedics, The First Affiliated Hospital, China Medical University, Shenyang, China.
Cong
C
Lin
Department of Orthopedics, The Second Affiliated Hospital, Shenyang Medical College, Shenyang, China.
Pei
P
Zifeng