Intervertebral Disc Regeneration: Influence of Growth Factors on Differentiation of Human Mesenchymal Stem Cells (hMSC)

Ehlicke, Franziska; Freimark, Denise; Heil, Birthe; Dorresteijn, Adriaan; Czermak, Peter

doi:10.1177/039139881003300409

Cited by 47 publications

(34 citation statements)

References 20 publications

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“…However, the differentiation of MSCs depends on various biological microenvironmental factors. Growth factors including TGF-β, IGF-1, FGF-2 and PDGF have been shown to induce the differentiation of MSCs into NP-like cells [25,28]. MSCs cultured under hypoxic conditions (2-3% oxygen) showed enhanced NP-like and chondrogenic differentiation [25,127,128].…”

Section: The Effect Of Gdf-5 On the Differentiation Of Mscs Toward Anmentioning

confidence: 99%

“…The differentiation of MSCs toward an NP-like phenotype has been shown to be induced by growth factors, co-culture with disc cells, and hypoxia [25,26,27]. TGF-β [25], IGF-1, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor-BB [28] and GDF-5 [29,][30] possessed the ability to induce NP-like differentiation of MSCs. The gene expression profiles of these induced MSCs resembled those of native IVD tissue more closely than those of joint cartilage [31].…”

Section: Introductionmentioning

confidence: 99%

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Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Feng

Liu

Yang

et al. 2015

Cell Physiol Biochem

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Intervertebral disc degeneration (IDD) is a widely recognized contributor to low back pain (LBP). The Prevention or reversal of IDD is a potential treatment for LBP. Unfortunately, current treatments for IDD are aimed at relieving symptoms rather than regenerating disc structure or function. Recently, the injection of growth factors and mesenchymal stem cell (MSC) transplantation have been shown to be promising biological therapies for IDD. Growth factors stimulate the proliferation of and matrix synthesis by intervertebral disc (IVD) cells, leading to the regeneration of degenerative discs. Growth factors, hypoxia and co-culture with nucleus pulposus (NP) cells induce MSCs to differentiate toward an NP-like phenotype, which can increase the number of functional cells in the IVD or enhance the function of endogenous disc cells to facilitate IVD regeneration. Therefore, the emerging roles of growth factors in IVD regeneration have piqued the interest of researchers. Growth factors including transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1) and growth and differentiation factor-5 (GDF-5), among others, have been demonstrated to enhance anabolism in IVD cells and to induce NP-like differentiation of MSCs. However, the injection of TGF, IGF and FGF into human IVDs may induce unwanted blood vessel ingrowth, which accelerates the process of IDD, the injection of GDF-5 may not have the same effect. This finding suggests that GDF-5 is a preferable growth factor for use in IDD treatment compared with TGF, IGF and FGF. The GDF-5 gene is one of the few growth factor genes that have been found to be associated with IDD thus far; moreover, the GDF-5 gene defects lead to collagen and proteoglycan abnormalities in discs in mice, suggesting that GDF-5 contributes to the structural and functional maintenance of the IVD. This review is focused on the functions of GDF-5 in the IVD and on the association between GDF-5 and a genetic predisposition to IDD. The effects of GDF-5 on IVD regeneration and on MSC differentiation are also discussed. GDF-5 plays a crucial role in the pathogenesis of IDD and is a promising therapeutic agent for IDD. Additionally, stem cell transplantation has been shown to be a promising biological therapy for IDD.

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Section: The Effect Of Gdf-5 On the Differentiation Of Mscs Toward Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Feng

Liu

Yang

et al. 2015

Cell Physiol Biochem

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“…Multiple cytokines and growth factors, such as members of the TGF-β and bone morphogenetic protein families, insulin-like growth factor-1, and fibroblast growth factor-2 (Ehlicke et al, 2010;Luo et al, 2011), promote NP cells from ES cells or MSCs. Many of these cytokines and growth factors display a high degree of functional overlap.…”

Section: Discussionmentioning

confidence: 99%

Determination of the potential of induced pluripotent stem cells to differentiate into mouse nucleus pulposus cells in vitro

Liu¹,

Chen²,

Luo³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We determined the potential for induced pluripotent stem (iPS) cells to differentiate into nucleus pulposus (NP)-like cells in mice. iPS cells were generated from tail-tip fibroblasts. We used a pellet culture model with the aim of determining the applicability of iPS cell-based therapy to intervertebral disc degeneration (IVD). The cell pellet was cultured in an NP cell basal medium comprising Dulbecco's modified Eagle's medium supplemented with transforming growth factor beta 1, dexamethasone, ascorbate-2-phosphate, and 1% ITS-Premix. The pellet was evaluated by quantitative reverse transcription polymerase chain (2015) reaction, immunohistochemical staining, and biochemical composition. The differentiation of iPS cells into NP cells was demonstrated by the protein and mRNA expression levels of proteoglycan, collagen II, aggrecan, and CD24. Furthermore, increased hydroxyproline content and dimethylmethylene blue staining demonstrated that the collagen II and glycosaminoglycan content in the NP cells increased with time. We have shown that cultured mouse iPS cells can be induced to differentiate into NP cells. Such proofof-concept opens up the possibility of producing patient-specific NP cells in a relatively simple and straightforward manner with high efficiency. We are confident that such cells could be immediately useful for the study of IVD disease.

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“…At a pharmaco-molecular level, the study aimed to analyze the effects of nimodipine on chondroadherin (CHAD) (19,20); NP-specific marker proteins; type II collagen (COL2A1) (21), which is responsible for extracellular matrix development; and hypoxia-inducible factor 1 alpha (HIF 1α) (22), which is induced by hypoxia and is a continuous expression of the NP-specific marker.…”

Section: Introductionmentioning

confidence: 99%

Do we damage nucleus pulposus tissue while treating cerebrovascular ischemic neurological deficits with nimodipine?

Karaarslan¹,

Yılmaz²,

Şirin³

et al. 2018

J Turgut Ozal Med Cent

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Aim: Nimodipine is used to prevent cerebrovascular-originated ischemic neurological deficits, yet its effects on nucleus pulposus (NP) cells or annulus fibrosus (AF) cells weren't studied. This study aimed to examine nimodipine's effects on vitality and proliferation of chondroadherin (CHAD), type II collagen (COL2A1), and hypoxia-inducible factor 1 alpha (HIF 1α) gene expression in human primary NP/AF cells. Material and Methods: NP/AF cell cultures obtained from 6 patients who underwent microdiscectomy were treated with 100 µMolar nimodipine and analyzed at 0, 24, and 48 h. Data were evaluated using one-way ANOVA and post-hoc Tukey HSD with 95% confidence interval. Results: We observed suppressed cell proliferation and increased necrosis in nimodipine-treated NP/AF cell cultures, especially degenerated tissue. COL2A1 gene expression wasn't detected in any experimental groups. CHAD and HIF 1α expression had timedependent decreases in control. CHAD and HIF 1α expression were found to decrease at 24h, but increased at 48h in degenerated tissue. In nimodipine-applied intact tissues, CHAD expression was stable at 24h but 1.62 times higher than control at 48h. HIF 1α levels were lower than control. Conclusion: In nimodipine-treated degenerated AF/NP cultures, CHAD and HIF 1α expressions had time-dependent decreases. However, after complete RT-PCR data evaluation, no correlation between nimodipine application and gene expression occurred.

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Intervertebral Disc Regeneration: Influence of Growth Factors on Differentiation of Human Mesenchymal Stem Cells (hMSC)

Cited by 47 publications

References 20 publications

Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

Determination of the potential of induced pluripotent stem cells to differentiate into mouse nucleus pulposus cells in vitro

Do we damage nucleus pulposus tissue while treating cerebrovascular ischemic neurological deficits with nimodipine?

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