PMID- 38003216
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240210
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 22
DP  - 2023 Nov 7
TI  - Enhanced Intervertebral Disc Repair via Genetically Engineered Mesenchymal Stem 
      Cells with Tetracycline Regulatory System.
LID - 10.3390/ijms242216024 [doi]
LID - 16024
AB  - The therapeutic potential of Mesenchymal stem cells (MSCs) for the treatment of 
      Intervertebral disc (IVD) degeneration can be enhanced by amplifying specific 
      cytokines and proteins. This study aimed to investigate the therapeutic potential 
      of tetracycline-off system-engineered tonsil-derived mesenchymal stem cells 
      (ToMSC-Tetoff-TGFbeta1-IGF1-BMP7) for treating intervertebral disc (IVD) 
      degeneration. ToMSCs were isolated from a tonsillectomy patient and genetically 
      modified with four distinct plasmids via CRISPR/Cas9-mediated knock-in gene 
      editing. Transgene expression was confirmed through immunofluorescence, western 
      blots, and an enzyme-linked immunosorbent assay for transforming growth factor 
      beta 1 (TGFbeta1) protein secretion, and the effect of MSC-TetOff-TGFbeta1-IGF1-BMP7 on 
      disc injury was assessed in a rat model. The ToMSC-Tetoff-TGFbeta1-IGF1-BMP7 
      treatment exhibited superior therapeutic effects compared to ToMSC-TGFbeta1, and 
      ToMSC-SDF1alpha implantation groups, stimulating the regeneration of nucleus pulposus 
      (NP) cells crucial for IVD. The treatment showed potential to restore the 
      structural integrity of the extracellular matrix (ECM) by upregulating key 
      molecules such as aggrecan and type II collagen. It also exhibited 
      anti-inflammatory properties and reduced pain-inducing neuropeptides. 
      ToMSC-Tetoff-TGFbeta1-IGF1-BMP7 holds promise as a novel treatment for IVD 
      degeneration. It appears to promote NP cell regeneration, restore ECM structure, 
      suppress inflammation, and reduce pain. However, more research and clinical 
      trials are required to confirm its therapeutic potential.
FAU - Kim, Yeji
AU  - Kim Y
AD  - Research Competency Milestones Program of School of Medicine, CHA University 
      School of Medicine, Seongnam-si 13496, Republic of Korea.
FAU - An, Seong Bae
AU  - An SB
AD  - Department of Neurosurgery, CHA University School of Medicine, CHA Bundang 
      Medical Center, Seongnam-si 13496, Republic of Korea.
FAU - Lee, Sang-Hyuk
AU  - Lee SH
AD  - Department of Biomedical Science, Graduate School of CHA University, Seongnam-si 
      13496, Republic of Korea.
FAU - Lee, Jong Joo
AU  - Lee JJ
AUID- ORCID: 0000-0003-0905-0330
AD  - Department of Medicine, Graduate School, Kyung Hee University, Seoul 02453, 
      Republic of Korea.
AD  - Department of Neurosurgery, Kangbuk Samsung Hospital, Sungkyunkwan University 
      College of Medicine, Seoul 03181, Republic of Korea.
FAU - Kim, Sung Bum
AU  - Kim SB
AD  - Department of Neurosurgery, Kyung Hee University, Seoul 02453, Republic of Korea.
FAU - Ahn, Jae-Cheul
AU  - Ahn JC
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, CHA University School of 
      Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Republic of Korea.
FAU - Hwang, Dong-Youn
AU  - Hwang DY
AD  - Department of Biomedical Science, Graduate School of CHA University, Seongnam-si 
      13496, Republic of Korea.
AD  - Department of Microbiology, School of Medicine, CHA University, Seongnam-si 
      13496, Republic of Korea.
FAU - Han, Inbo
AU  - Han I
AUID- ORCID: 0000-0002-0834-9325
AD  - Department of Neurosurgery, CHA University School of Medicine, CHA Bundang 
      Medical Center, Seongnam-si 13496, Republic of Korea.
LA  - eng
GR  - 27304C0002/ES/NIEHS NIH HHS/United States
GR  - 27306C0002/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20231107
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - F8VB5M810T (Tetracycline)
RN  - 0 (Anti-Bacterial Agents)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - *Intervertebral Disc/metabolism
MH  - *Intervertebral Disc Degeneration/genetics/therapy/metabolism
MH  - *Nucleus Pulposus/metabolism
MH  - Tetracycline/pharmacology
MH  - Anti-Bacterial Agents/pharmacology
MH  - *Mesenchymal Stem Cells/metabolism
PMC - PMC10671788
OTO - NOTNLM
OT  - Tet-off
OT  - intervertebral disc regeneration
OT  - mesenchymal stem cells
OT  - tetracyclin (Tet) regulatory system
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/25 12:43
MHDA- 2023/11/27 12:44
PMCR- 2023/11/07
CRDT- 2023/11/25 01:14
PHST- 2023/09/30 00:00 [received]
PHST- 2023/10/28 00:00 [revised]
PHST- 2023/11/01 00:00 [accepted]
PHST- 2023/11/27 12:44 [medline]
PHST- 2023/11/25 12:43 [pubmed]
PHST- 2023/11/25 01:14 [entrez]
PHST- 2023/11/07 00:00 [pmc-release]
AID - ijms242216024 [pii]
AID - ijms-24-16024 [pii]
AID - 10.3390/ijms242216024 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Nov 7;24(22):16024. doi: 10.3390/ijms242216024.