Notochordal cell matrix as a therapeutic agent for intervertebral disc regeneration

Stefan de Vries, Marina van Doeselaar, Björn Meij, Marianna Tryfonidou, Keita Ito (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
1 Downloads (Pure)

Abstract

Notochordal cells (NCs) reside in the core of the healthy disc and produce soluble factors that can stimulate nucleus pulposus cells (NPCs). These NC-derived factors may be applied in intervertebral disc regeneration for treatment of low-back pain. However, identification of the active soluble factors is challenging. Therefore a novel approach to directly use porcine NC-rich NP matrix (NCM) is introduced. We explored porcine NCM's anabolic effects on bovine NPCs harvested from caudal discs of adolescent and adult (2-2.5 vs. 4-6 year old) cows. NC-conditioned medium (NCCM) and NCM were produced from porcine NC-rich NP tissue. Bovine NPCs were cultured in alginate beads for 4 weeks in base medium (BM), NCCM, and NCM to investigate NCM's regenerative potential. Porcine NCM increased glycosaminoglycan (GAG) content of both adolescent and adult bovine NPCs. This was through increased proliferation of adolescent bovine NPCs, whereas in adult bovine NPCs, it was mostly through increased GAG production per NPC. Furthermore, adolescent bovine NPCs were cultured in BM and porcine NCM treated with interleukin (IL)-1β to investigate NCM's potential in an inflammatory environment. Addition of IL-1β enhanced IL1β and CXCL8 (IL8) gene expression, while NCM diminished IL1β gene expression. IL-1β reduced GAG and DNA content, but the addition of NCM relative to BM improved GAG and DNA content. Altogether, porcine NCM exerts bovine NPC-age dependent effects, and NCM's anabolic effect on adult NPCs is stronger compared with NCCM. Furthermore, porcine NCM induced an anabolic response of bovine NPCs in an inflammatory environment and may have anti-inflammatory properties. Therefore, NCM has potential in a regenerative therapy for disc degeneration, and warrants additional in vivo studies.

Original languageEnglish
Pages (from-to)830-841
Number of pages12
JournalTissue engineering. Part A
Volume25
Issue number11-12
DOIs
Publication statusPublished - 1 Jun 2019

Fingerprint

Intervertebral Disc
Glycosaminoglycans
Regeneration
Conditioned Culture Medium
Interleukin-1
Anabolic Agents
Gene expression
DNA
Swine
Alginate
Therapeutics
Interleukin-8
Anti-Inflammatory Agents
Tissue
Cultured Cells
Nucleus Pulposus
Gene Expression
Intervertebral Disc Degeneration
Low Back Pain

Keywords

  • extracellular matrix
  • notochordal cells
  • nucleus pulposus
  • regenerative medicine

Cite this

de Vries, Stefan ; van Doeselaar, Marina ; Meij, Björn ; Tryfonidou, Marianna ; Ito, Keita. / Notochordal cell matrix as a therapeutic agent for intervertebral disc regeneration. In: Tissue engineering. Part A. 2019 ; Vol. 25, No. 11-12. pp. 830-841.
@article{99df393ec59e4cdea1ff56896bb1d4d2,
title = "Notochordal cell matrix as a therapeutic agent for intervertebral disc regeneration",
abstract = "Notochordal cells (NCs) reside in the core of the healthy disc and produce soluble factors that can stimulate nucleus pulposus cells (NPCs). These NC-derived factors may be applied in intervertebral disc regeneration for treatment of low-back pain. However, identification of the active soluble factors is challenging. Therefore a novel approach to directly use porcine NC-rich NP matrix (NCM) is introduced. We explored porcine NCM's anabolic effects on bovine NPCs harvested from caudal discs of adolescent and adult (2-2.5 vs. 4-6 year old) cows. NC-conditioned medium (NCCM) and NCM were produced from porcine NC-rich NP tissue. Bovine NPCs were cultured in alginate beads for 4 weeks in base medium (BM), NCCM, and NCM to investigate NCM's regenerative potential. Porcine NCM increased glycosaminoglycan (GAG) content of both adolescent and adult bovine NPCs. This was through increased proliferation of adolescent bovine NPCs, whereas in adult bovine NPCs, it was mostly through increased GAG production per NPC. Furthermore, adolescent bovine NPCs were cultured in BM and porcine NCM treated with interleukin (IL)-1β to investigate NCM's potential in an inflammatory environment. Addition of IL-1β enhanced IL1β and CXCL8 (IL8) gene expression, while NCM diminished IL1β gene expression. IL-1β reduced GAG and DNA content, but the addition of NCM relative to BM improved GAG and DNA content. Altogether, porcine NCM exerts bovine NPC-age dependent effects, and NCM's anabolic effect on adult NPCs is stronger compared with NCCM. Furthermore, porcine NCM induced an anabolic response of bovine NPCs in an inflammatory environment and may have anti-inflammatory properties. Therefore, NCM has potential in a regenerative therapy for disc degeneration, and warrants additional in vivo studies.",
keywords = "extracellular matrix, notochordal cells, nucleus pulposus, regenerative medicine",
author = "{de Vries}, Stefan and {van Doeselaar}, Marina and Bj{\"o}rn Meij and Marianna Tryfonidou and Keita Ito",
year = "2019",
month = "6",
day = "1",
doi = "10.1089/ten.tea.2018.0026",
language = "English",
volume = "25",
pages = "830--841",
journal = "Tissue engineering. Part A",
issn = "1937-3341",
publisher = "Mary Ann Liebert Inc.",
number = "11-12",

}

Notochordal cell matrix as a therapeutic agent for intervertebral disc regeneration. / de Vries, Stefan; van Doeselaar, Marina; Meij, Björn; Tryfonidou, Marianna; Ito, Keita (Corresponding author).

In: Tissue engineering. Part A, Vol. 25, No. 11-12, 01.06.2019, p. 830-841.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Notochordal cell matrix as a therapeutic agent for intervertebral disc regeneration

AU - de Vries, Stefan

AU - van Doeselaar, Marina

AU - Meij, Björn

AU - Tryfonidou, Marianna

AU - Ito, Keita

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Notochordal cells (NCs) reside in the core of the healthy disc and produce soluble factors that can stimulate nucleus pulposus cells (NPCs). These NC-derived factors may be applied in intervertebral disc regeneration for treatment of low-back pain. However, identification of the active soluble factors is challenging. Therefore a novel approach to directly use porcine NC-rich NP matrix (NCM) is introduced. We explored porcine NCM's anabolic effects on bovine NPCs harvested from caudal discs of adolescent and adult (2-2.5 vs. 4-6 year old) cows. NC-conditioned medium (NCCM) and NCM were produced from porcine NC-rich NP tissue. Bovine NPCs were cultured in alginate beads for 4 weeks in base medium (BM), NCCM, and NCM to investigate NCM's regenerative potential. Porcine NCM increased glycosaminoglycan (GAG) content of both adolescent and adult bovine NPCs. This was through increased proliferation of adolescent bovine NPCs, whereas in adult bovine NPCs, it was mostly through increased GAG production per NPC. Furthermore, adolescent bovine NPCs were cultured in BM and porcine NCM treated with interleukin (IL)-1β to investigate NCM's potential in an inflammatory environment. Addition of IL-1β enhanced IL1β and CXCL8 (IL8) gene expression, while NCM diminished IL1β gene expression. IL-1β reduced GAG and DNA content, but the addition of NCM relative to BM improved GAG and DNA content. Altogether, porcine NCM exerts bovine NPC-age dependent effects, and NCM's anabolic effect on adult NPCs is stronger compared with NCCM. Furthermore, porcine NCM induced an anabolic response of bovine NPCs in an inflammatory environment and may have anti-inflammatory properties. Therefore, NCM has potential in a regenerative therapy for disc degeneration, and warrants additional in vivo studies.

AB - Notochordal cells (NCs) reside in the core of the healthy disc and produce soluble factors that can stimulate nucleus pulposus cells (NPCs). These NC-derived factors may be applied in intervertebral disc regeneration for treatment of low-back pain. However, identification of the active soluble factors is challenging. Therefore a novel approach to directly use porcine NC-rich NP matrix (NCM) is introduced. We explored porcine NCM's anabolic effects on bovine NPCs harvested from caudal discs of adolescent and adult (2-2.5 vs. 4-6 year old) cows. NC-conditioned medium (NCCM) and NCM were produced from porcine NC-rich NP tissue. Bovine NPCs were cultured in alginate beads for 4 weeks in base medium (BM), NCCM, and NCM to investigate NCM's regenerative potential. Porcine NCM increased glycosaminoglycan (GAG) content of both adolescent and adult bovine NPCs. This was through increased proliferation of adolescent bovine NPCs, whereas in adult bovine NPCs, it was mostly through increased GAG production per NPC. Furthermore, adolescent bovine NPCs were cultured in BM and porcine NCM treated with interleukin (IL)-1β to investigate NCM's potential in an inflammatory environment. Addition of IL-1β enhanced IL1β and CXCL8 (IL8) gene expression, while NCM diminished IL1β gene expression. IL-1β reduced GAG and DNA content, but the addition of NCM relative to BM improved GAG and DNA content. Altogether, porcine NCM exerts bovine NPC-age dependent effects, and NCM's anabolic effect on adult NPCs is stronger compared with NCCM. Furthermore, porcine NCM induced an anabolic response of bovine NPCs in an inflammatory environment and may have anti-inflammatory properties. Therefore, NCM has potential in a regenerative therapy for disc degeneration, and warrants additional in vivo studies.

KW - extracellular matrix

KW - notochordal cells

KW - nucleus pulposus

KW - regenerative medicine

UR - http://www.scopus.com/inward/record.url?scp=85067286846&partnerID=8YFLogxK

U2 - 10.1089/ten.tea.2018.0026

DO - 10.1089/ten.tea.2018.0026

M3 - Article

C2 - 29739272

AN - SCOPUS:85067286846

VL - 25

SP - 830

EP - 841

JO - Tissue engineering. Part A

JF - Tissue engineering. Part A

SN - 1937-3341

IS - 11-12

ER -