Lovastatin Promotes Redifferentiation of Human Nucleus Pulposus Cells During Expansion in Monolayer Culture

Hu, Ming-Hsiao; Hung, Li-Wei; Yang, Shuai; Sun, Yuan-Hui; Shih, Tiffany Ting-Fang; Lin, Feng-Huei

doi:10.1111/j.1525-1594.2010.01070.x

Cited by 15 publications

(14 citation statements)

References 19 publications

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“…Several anabolic factors have been used to enhance synthesis of proteoglycans and type II collagen of NP cells . However, human NP cells at different stages of degeneration may respond differently to an anabolic factor .…”

Section: Discussionmentioning

confidence: 99%

“…40 Several anabolic factors have been used to enhance synthesis of proteoglycans and type II collagen of NP cells. 16,17,42 However, human NP cells at different stages of degeneration may respond differently to an anabolic factor. 21 Even though the cells originated from the same sources, human NP cells cultivated under different isolationexpansion processes may exert a different level of response to the same exogenous stimulus, such as the expression of type II collagen after lovastatin pretreatment in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…The following experiment was designed to investigate if the hypoxic or normoxic isolation-expansion procedures would affect the responsiveness of human NP cells to later exogenous treatments. Before being aggregated into microtissues, NP cells in hypoxic or normoxic monolayer were treated with 10 ng/mL transforming growth factor (TGF)-b1 or 5 lM lovastatin for 72 h. 16,17 After one week of incubation in microtissues, gene expression levels of AGC and type II collagen were measured by quantitative RT-PCR. Gene expression values for NP cells subjected to either pretreatment were first normalized to cells without pretreatment in each group.…”

Section: Responsiveness To Pretreatment Of Tgf-b1 or Lovastatinmentioning

confidence: 99%

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The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

Yang

et al. 2017

J Biomedical Materials Res

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Nucleus pulposus (NP) cells locate in the center of avascular intervertebral discs, and thus have presumably adapted to a hypoxic environment. The purpose of this study was to investigate the influences of hypoxic condition, during isolation-expansion of human NP cells, on the cellular proliferation and extracellular matrix (ECM) synthesis in later three-dimensional cultures. Human NP tissues were obtained from patients who underwent lumbar disc surgeries. Immediately after retrieval, NP tissues from each patient were divided into two aliquots for in vitro cultivation either under classical normoxic (21% O ) or hypoxic (3.5% O ) condition. After isolation-expansion processes, microtissues of NP cells were formed and the analysis was performed after one-week culture. Experiments of pretreatment with TGF-β1 or lovastatin were designed to investigate if the isolation-expansion conditions affect the responsiveness to later exogenous treatments. Hypoxic isolation-expansion stimulated NP cell proliferation during monolayer culture. Hypoxia also upregulated mRNA levels of SOX9 and HIF-1α but downregulated type X collagen as well as improved aggrecan and type II collagen synthesis. Although TGF-β1 had no substantial effect, lovastatin pretreatment showed a greater enhancement on type II collagen expression in hypoxic group. Normoxia negatively affected the biochemical composition of regenerated ECM attributable to downregulation of SOX9 and HIF-1α, while hypoxia enhanced cellular proliferation, improved matrix production, and maintained a functional phenotype of NP cells. Hypoxic isolation-expansion of human NP cells is important to achieve better regenerative cells for later cultivation or cell transplantation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1575-1582, 2017.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Responsiveness To Pretreatment Of Tgf-b1 or Lovastatinmentioning

confidence: 99%

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The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

Yang

et al. 2017

J Biomedical Materials Res

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“…Ming‐Hsiao Hu et al. (154) of the National Taiwan University Hospital, Douliou City, Taiwan investigated whether lovastatin reverses “dedifferentiation” of human nucleus pulposus (NP) cells during monolayer expansion. Expression of genes encoding type II collagen and transcription factor SOX9 in these cells was upregulated by lovastatin, with maximal stimulations observed at 5 µM, whereas type I collagen gene expression was suppressed by the drug with maximal inhibitions observed at 5–10 µM.…”

Section: Tissue Engineeringmentioning

confidence: 99%

Artificial Organs 2011: A Year in Review

Malchesky¹

2012

Artificial Organs

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In this Editor's Review, articles published in 2011 are organized by category and briefly summarized. As the official journal of The International Federation for Artificial Organs, The International Faculty for Artificial Organs, and the International Society for Rotary Blood Pumps, Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level."Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ replacement, recovery, and regeneration from all over the world. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers, the quality expected from such a journal would not be possible. We also express our special thanks to our Publisher, Wiley-Blackwell, for their expert attention and support in the production and marketing of Artificial Organs. In this Editor's Review, that historically has been widely well-received by our readership, we aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ replacement, recovery, and regeneration. We look forward to recording further advances in the coming years.

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“…This issue is further complicated by the extensive passaging procedures required to obtain sufficient numbers of cells for in vivo implantation. When passaged in monolayer, NP cells (NPCs) are known to proliferate slowly [18] and undergo increasing dedifferentiation [19][20][21]. Cells from the degenerated NP also become increasingly senescent, which makes them minimally responsive to a growth factor or cytokine stimulation; the cells display an increased catabolic metabolism characterized by the increased production of matrix degrading enzymes [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Reconstruction of an In Vitro Niche for the Transition from Intervertebral Disc Development to Nucleus Pulposus Regeneration

Shoukry

Pei

2013

Stem Cells and Development

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The nucleus pulposus (NP) plays a prominent role in both the onset and progression of intervertebral disc degeneration. While autologous repair strategies have demonstrated some success, their in vitro culture system is outdated and insufficient for maintaining optimally functioning cells through the required extensive passaging. Consequently, the final population of cells may be unsuitable for the overwhelming task of repairing tissue in vivo and could result in subpar clinical outcomes. Recent work has identified synovium-derived stem cells (SDSCs) as a potentially important new candidate. This population of precursors can promote matrix regeneration and additionally restore the balance of catabolic and anabolic metabolism of surrounding cells. Another promising application is their ability to produce an extracellular matrix in vitro that can be modified via decellularization to produce a tissue-specific substrate for efficient cell expansion, while retaining chondrogenic potential. When combined with hypoxia, soluble factors, and other environmental regulators, the resultant complex microenvironment will more closely resemble the in vivo niche, which further improves the cell capacity, even after extensive passaging. In this review, the adaptive mechanisms NP cells utilize in vivo are considered for insight into what factors are important for constructing a tissue-specific in vitro niche. Evidence for the use of SDSCs for NP regeneration is also discussed. Many aspects of NP behavior are still unknown, which could lead to future work yielding key information on producing sufficient numbers of a high-quality NPspecific population that is able to regenerate deteriorated NP in vivo.

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Lovastatin Promotes Redifferentiation of Human Nucleus Pulposus Cells During Expansion in Monolayer Culture

Cited by 15 publications

References 19 publications

The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

Artificial Organs 2011: A Year in Review

Reconstruction of an In Vitro Niche for the Transition from Intervertebral Disc Development to Nucleus Pulposus Regeneration

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