Biological Sciences Division
Published March 7, 2025 | Version v1
Journal article Open

An Intervertebral Disc (IVD) Regeneration Model Using Human Nucleus Pulposus Cells (iHNPCs) and Annulus Fibrosus Cells (iHAFCs)

Creators

  • 1. University of Chicago
  • 2. Pennsylvania State University
  • 3. National Clinical Research Center for Child Health and Disorders
  • 4. Westlake University
  • 5. Beijing Hospital

Description

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.

Data availability

The data that support the findings of this study are available in the supplementary material of this article.

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Intervertebral-Disc-IVD-Regeneration-Model.pdf

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Additional details

Identifiers

DOI
10.1002/adhm.202403742
Other
oai:uchicago.tind.io:14703

Funding

National Key Research and Development Plan
2022YFC3601905
National Key Research and Development Plan
2022YFC3601900
National Institutes of Health
CA226303
National Institutes of Health
DE030480
University of Chicago Medicine Comprehensive Cancer Center
Cancer Center Support Grant
National Center for Advancing Translational Sciences
5UL1TR002389
Unknown funder
Mabel Green Myers Research Endowment Fund
University of Chicago
Orthopaedics Alumni Fund

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Orthopaedic Surgery and Rehabilitation Medicine, Surgery