Evidence map›Paper›PMID 40999513›Full record

ArticleStem cell research & therapy2025

Enhanced disc regeneration through CRISPR/Cas9-mediated SOX9 and TGFβ1 coexpression in tonsil-derived mesenchymal stromal cells.

Somin Lee, Yerin Yu, Dong Hee Kim, Minsung Bock, Yeji Kim, Seong Bae An, Hyemin Choi, Hae Eun Shin, Dong-Youn Hwang, Inbo Han

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Somin Lee *Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Yerin Yu *Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Dong Hee Kim *Department of Biomedical Science, Graduate School of CHA University, Seongnam-si, 13496, Republic of Korea.
Minsung BockDepartment of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Yeji KimDepartment of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Seong Bae AnDepartment of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Hyemin ChoiDepartment of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Hae Eun ShinDepartment of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea.
Dong-Youn HwangDepartment of Biomedical Science, Graduate School of CHA University, Seongnam-si, 13496, Republic of Korea. hdy@cha.ac.kr.
Inbo HanDepartment of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13496, Gyeonggi-do, Republic of Korea. hanib@cha.ac.kr.ORCID http://orcid.org/0000-0002-0834-9325

Funding

Korean Cell-Based Artificial Blood Project funded by the Korean government (The Minis-try of Science and ICT, The Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) RS-2023-KH141187National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT: Ministry of Science and ICT) RS-2024-00347403
6 · The paper itself

Abstract

backgroundIntervertebral disc (IVD) degeneration, a primary cause of chronic low back pain, currently lacks treatments that target its underlying pathological mechanisms. Tonsil-derived mesenchymal stromal cells (ToMSCs) have shown promise for IVD regeneration; however, their therapeutic potential is limited by the harsh microenvironment of degenerated discs. This study investigated whether ToMSCs engineered to co‐overexpress SOX9 and TGFβ1 using a tetracycline‐off (Tet‐off) regulatory system could enhance extracellular matrix (ECM) restoration and reduce inflammation in degenerative IVDs.

methodsWe used CRISPR/Cas9 technology to generate ToMSCs that express SOX9, TGFβ1, or both factors under Tet-off regulation. Gene expression was confirmed by Western blot and qRT-PCR analyses. In vitro studies assessed chondrogenic differentiation capacity, while in vivo assessments were performed using a rat tail needle puncture model of IVD degeneration. After administering the CRISPR-engineered ToMSCs, we monitored mechanical allodynia with the von Frey test over six weeks. Therapeutic outcomes were evaluated through T2‐weighted MRI and histological analysis.

resultsIn vitro experiments showed that ToMSCs co-expressing SOX9 and TGFβ1 exhibited superior chondrogenic differentiation compared to cells expressing a single factor. In vivo studies demonstrated that dual-factor expressing ToMSCs significantly improved disc hydration (as confirmed by MRI), enhanced ECM synthesis—particularly aggrecan and type II collagen—and reduced inflammation compared to single-factor treatments. These improvements were accompanied by reduced mechanical allodynia, indicating functional recovery.

conclusionOur study demonstrates that ToMSCs engineered to co-express SOX9 and TGFβ1 effectively promote IVD regeneration by enhancing ECM production and reducing inflammation. This dual-factor approach represents a promising therapeutic strategy for treating degenerative disc disease and warrants further investigation for clinical application.

Indexed as

CRISPR-Cas SystemsIntervertebral DiscIntervertebral Disc DegenerationMesenchymal Stem CellsPalatine TonsilRegenerationSOX9 Transcription FactorTransforming Growth Factor beta1AnimalsCell DifferentiationChondrogenesisHumansMaleRatsRats, Sprague-DawleySOX9 protein, humanSOX9 Transcription FactorTransforming Growth Factor beta1CRISPR/Cas9Intervertebral disc degenerationSOX9Tetracycline-off systemTGFβ1Tonsil-derived mesenchymal stromal cells

Identifiers

PMID40999513
PMCPMC12465725

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.