Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma

Wei Hong Chen, Hen Yu Liu, Wen Cheng Lo, Shinn Chih Wu, Chau Hwa Chi, Hsueh Yuan Chang, Shih Hsiang Hsiao, Chih Hsiung Wu, Wen Ta Chiu, Bao Ji Chen, Win Ping Deng

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration.

Original languageEnglish
Pages (from-to)5523-5533
Number of pages11
JournalBiomaterials
Volume30
Issue number29
DOIs
Publication statusPublished - Oct 2009

Fingerprint

Platelet-Rich Plasma
Intervertebral Disc
Platelets
Stem cells
Mesenchymal Stromal Cells
Cell culture
Regeneration
Chondrogenesis
Intervertebral Disc Degeneration
Plasmas
Screening
Animals
Swine
Animal Models
Chymopapain
Aggrecans
Stem Cell Factor
Organ Culture Techniques
Therapeutics
Osteogenesis

Keywords

  • Intervertebral disc
  • Mesenchymal stem cell
  • Nucleus pulposus
  • Platelet-rich plasma
  • Regeneration

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. / Chen, Wei Hong; Liu, Hen Yu; Lo, Wen Cheng; Wu, Shinn Chih; Chi, Chau Hwa; Chang, Hsueh Yuan; Hsiao, Shih Hsiang; Wu, Chih Hsiung; Chiu, Wen Ta; Chen, Bao Ji; Deng, Win Ping.

In: Biomaterials, Vol. 30, No. 29, 10.2009, p. 5523-5533.

Research output: Contribution to journalArticle

Chen, Wei Hong ; Liu, Hen Yu ; Lo, Wen Cheng ; Wu, Shinn Chih ; Chi, Chau Hwa ; Chang, Hsueh Yuan ; Hsiao, Shih Hsiang ; Wu, Chih Hsiung ; Chiu, Wen Ta ; Chen, Bao Ji ; Deng, Win Ping. / Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. In: Biomaterials. 2009 ; Vol. 30, No. 29. pp. 5523-5533.
@article{69e233139307427286185c7246a3aa73,
title = "Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma",
abstract = "An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration.",
keywords = "Intervertebral disc, Mesenchymal stem cell, Nucleus pulposus, Platelet-rich plasma, Regeneration",
author = "Chen, {Wei Hong} and Liu, {Hen Yu} and Lo, {Wen Cheng} and Wu, {Shinn Chih} and Chi, {Chau Hwa} and Chang, {Hsueh Yuan} and Hsiao, {Shih Hsiang} and Wu, {Chih Hsiung} and Chiu, {Wen Ta} and Chen, {Bao Ji} and Deng, {Win Ping}",
year = "2009",
month = "10",
doi = "10.1016/j.biomaterials.2009.07.019",
language = "English",
volume = "30",
pages = "5523--5533",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier Science Ltd",
number = "29",

}

TY - JOUR

T1 - Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma

AU - Chen, Wei Hong

AU - Liu, Hen Yu

AU - Lo, Wen Cheng

AU - Wu, Shinn Chih

AU - Chi, Chau Hwa

AU - Chang, Hsueh Yuan

AU - Hsiao, Shih Hsiang

AU - Wu, Chih Hsiung

AU - Chiu, Wen Ta

AU - Chen, Bao Ji

AU - Deng, Win Ping

PY - 2009/10

Y1 - 2009/10

N2 - An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration.

AB - An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration.

KW - Intervertebral disc

KW - Mesenchymal stem cell

KW - Nucleus pulposus

KW - Platelet-rich plasma

KW - Regeneration

UR - http://www.scopus.com/inward/record.url?scp=68549090542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68549090542&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2009.07.019

DO - 10.1016/j.biomaterials.2009.07.019

M3 - Article

VL - 30

SP - 5523

EP - 5533

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 29

ER -