Mesenchymanl Stem Cell Based Intradiscal Gene Therapy: Therapeutic Implication in Degenerative Disc Disease.
10.4184/jkss.2004.11.2.67
- Author:
Hyang KIM
1
;
Un Hye KWON
;
Kwang Il LEE
;
Ki Hong SONG
;
Sung Yeop SHIN
;
Si Young PARK
;
Jin Oh PARK
;
Hwan Mo LEE
;
Seong Hwan MOON
Author Information
1. Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea. shmoon@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Mesenchymal stem cell;
disc cell;
TGF-b1;
adenovirus;
gene therapy
- MeSH:
Adenoviridae;
Aggrecans;
Cell- and Tissue-Based Therapy;
Collagen;
Collagen Type I;
Collagen Type II;
DNA;
DNA, Complementary;
Genetic Therapy*;
Humans;
Intervertebral Disc;
Mesenchymal Stromal Cells;
Phenotype;
Proteoglycans;
Regeneration;
RNA, Messenger;
Stem Cells*;
Transforming Growth Factor beta1
- From:Journal of Korean Society of Spine Surgery
2004;11(2):67-76
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
STUDY DESIGN: In-vitro experiments using human mesenchymal stem cells (MSCs), intervertebral disc (IVD) cells and type 5 adenovirus/transforming growth factor-beta1 construct (Ad/TGF-beta1). OBJECTIVES: To determine the effect of MSC-based gene therapy for matrix regeneration of IVD cells. SUMMARY OF LITERATURE REVIEW: MSCs are known to be multipotent in tissue regeneration. In degeneration of IVD, cellular replacement with genetic modification other than that of IVD cells may prove an enhanced mechanism for the regeneration of MATERIALS AND METHODS: MSCs and IVD cells were cultured and an adenovirus construct containing TGF-beta1 cDNA (Ad/TGF-beta1) was also produced. In the first step, the MSCs were transduced with Ad/TGF-beta1, then mixed with IVD cells in various proportions and three dimensionally cultured. [methyl-(3)H]Thymidine and [(35)S]Sulfur incorporation for DNA and proteoglycan synthesis, respectively, were measured. RT-PCR was performed to assess the aggrecan and collagen types I and II mRNA RESULTS: Mixed cultures of MSC and IVD cells showed relatively similar amounts of newly synthesized proteoglycan compared with cultures of IVD cells only. In mixed cultures transduced with Ad/TGF-beta1, there were significant decreases in newly synthesized proteoglycan with increasing the proportions of MSCs, which was also found with the aggrecan and collagen type II mRNA expressions. However, the collagen type I mRNA expression increased with increased proportions of MSCs transduced with Ad/TGF-beta1. CONCLUSION: Cell therapy with MSCs and IVD cells provided a mechanism for cellular augmentation. However, MSC-based gene therapy coupled with IVD cells did not maintain a chondrogenic phenotype.
