An Intervertebral Disc (IVD) Regeneration Model Using Human Nucleus Pulposus Cells (iHNPCs) and Annulus Fibrosus Cells (iHAFCs)
Intervertebral disc (IVD) degeneration (IVDD), primarily caused by nucleus pulposus (NP) dehydration, leads to low back pain. While current treatments focus on symptom management or surgical intervention, tissue engineering using IVD-derived cells, biofactors, and scaffolds offers a promising regenerative approach. Here, human NP cells (NPCs) and annulus fibrosus cells (AFCs) are immortalized with human telomerase reverse transcriptase (hTERT), generating immortalized NPCs (iHNPCs) and AFCs (iHAFCs). These cells express NP and AF-specific markers, are reversible via FLP recombinase, and are non-tumorigenic. iHAFCs exhibit osteogenic potential, while iHNPCs show chondrogenic differentiation. A 3D-printed citrate-based scaffold was employed to develop an IVD regeneration model, with BMP9-stimulated iHAFCs in the peripheral region and BMP2-stimulated iHNPCs in the central region. Histological analysis revealed bone formation in the iHAFC region and cartilage formation in the iHNPC region, mimicking the natural IVD structure. Additionally, an ex vivo spine fusion model demonstrated robust bone formation in iHAFC-treated segments. These findings highlight the potential of iHAFCs and iHNPCs as valuable tools for IVD tissue engineering and regeneration.
Authors
- Russell R. Reid (ORCID: https://orcid.org/0000-0002-1111-4500)
- Ethan Gerhard
- Jiamin Zhong
- Jiaming Fan (ORCID: https://orcid.org/0000-0001-8523-4188)
- Lewis L. Shi (ORCID: https://orcid.org/0000-0002-3533-8824)
- Changqi Luo (ORCID: https://orcid.org/0000-0002-7844-5646)
- Xingye Wu (ORCID: https://orcid.org/0000-0002-2265-7869)
- Chao Yu (ORCID: https://orcid.org/0000-0002-8391-4080)
- Jianjun Yang (ORCID: https://orcid.org/0000-0001-6785-9627)
- Hue H. Luu (ORCID: https://orcid.org/0000-0003-4562-0329)
- Ou Mei
- Tong‐Chuan He (ORCID: https://orcid.org/0000-0001-7721-3934)
- Guowei Shen (ORCID: https://orcid.org/0000-0002-1329-4058)
- Ya Wen (ORCID: https://orcid.org/0009-0001-2339-5549)
- Wulin You (ORCID: https://orcid.org/0009-0002-8839-8078)
- Yonghui Wang (ORCID: https://orcid.org/0000-0003-2904-7948)
- Hui Zhang (ORCID: https://orcid.org/0000-0003-1673-2444)
- Jingjing Li (ORCID: https://orcid.org/0000-0002-1410-9096)
- Qing Liu (ORCID: https://orcid.org/0009-0008-7432-9729)
- Yi Zhu (ORCID: https://orcid.org/0000-0002-2763-8691)
- Yang Bi (ORCID: https://orcid.org/0000-0001-7263-1002)
- Michael J. Lee (ORCID: https://orcid.org/0000-0001-5087-3991)
- Yi Shu (ORCID: https://orcid.org/0000-0003-4811-3621)
- Liangyuan Wen (ORCID: https://orcid.org/0000-0002-1616-5008)
- Usman Zeb
Institutions
- Jiangxi University of Traditional Chinese Medicine (CN)
- Pennsylvania State University (US)
- Nanjing University of Chinese Medicine (CN)
- Central South University (CN)
- Chongqing University (CN)
- Shanghai Jiao Tong University (CN)
- Capital Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- The University of Agriculture, Peshawar (PK)
- XinHua Hospital (CN)
- Westlake University (CN)
- Soochow University (CN)
- University of Chicago Medical Center (US)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Molecular Oncology (United States) (US)
- First Affiliated Hospital of Soochow University (CN)
- Chongqing Cancer Hospital (CN)
- Second People’s Hospital of Yibin (CN)
- Children's Hospital of Chongqing Medical University (CN)
- Nanjing Medical University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Advanced Healthcare Materials
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1002/adhm.202403742
- Citations
- 7
- Primary Topic
- Spine and Intervertebral Disc Pathology
- Type
- article
- Field-Weighted Citation Impact
- 10.30
Funders
- Foundation for the National Institutes of Health
- Key Technologies Research and Development Program