Differentiation of Human Ligamentum Flavum Stem Cells Toward Nucleus Pulposus-Like Cells Induced by Coculture System and Hypoxia

Han, Xiaobo; Zhang, Yanling; Li, Haiyin; Chen, Bin; Chang, Xian; Zhang, Wei; Kang, Yang; Zhou, Yue; Li, Changqing

doi:10.1097/brs.0000000000000882

Cited by 17 publications

(19 citation statements)

References 35 publications

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“…Expression of human specific markers, SOX9, ACAN, COL2, and FOXF1 in the NP of the treated IVDs, suggested that the transplanted human NPCs were viable and functionally active in the rabbit IVD. In fact, expression of acknowledged NP-specific genes, FOXF1, KRT19, PAX6, CA12 , and COMP , 9,56,57 was higher in the NP tissue of the IVDs transplanted with NPCs when compared to MSCs. Interestingly, KRT19 was found to be poorly expressed in NPCs in Vitro as discussed above.…”

Section: Discussionmentioning

confidence: 91%

Potential of Human Nucleus Pulposus-Like Cells Derived From Umbilical Cord to Treat Degenerative Disc Disease

et al. 2018

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Section: Discussionmentioning

confidence: 91%

Potential of Human Nucleus Pulposus-Like Cells Derived From Umbilical Cord to Treat Degenerative Disc Disease

et al. 2018

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“…The NP is an avascular tissue in a hypoxic environment, and it has been demonstrated that NP cells maintain their biosynthetic activities via constitutive expression of HIF-1α [18]. Our previous study has revealed that HIF-1α is a pivotal mediator of the development of the NP and has a prosurvival function in NP cells; this is because we find that there are many more cell deaths in the NP of NP-specifically HIF-1α deficient mice at 3 days, 6 weeks, and 12 weeks after birth [14].…”

Section: Discussionmentioning

confidence: 99%

CD24 identifies nucleus pulposus progenitors/notochordal cells for disc regeneration

Liu¹,

Zheng

Qi³

et al. 2018

J Biol Eng

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BackgroundCell-based therapy by transplantation of nucleus pulposus (NP) progenitor/notochordal cells has been proposed as a promising way to halt and reverse the progression of disc degeneration. Although some studies have provided a broad panel of potential markers associated with the phenotype of notochordal cells, suitability of these markers for isolation of notochordal cells for the treatment of disc degeneration is unclear.ResultsHere, we found that the number of CD24-positive NP cells significantly decreased with increasing severity of disc degeneration. In addition, CD24-positive NP cells were shown to maintain their multipotent differentiation and self-renewal potential in vitro and to abundantly express brachyury, SHH, and GLUT-1, suggesting that CD24-positive NP cells are the progenitor/notochordal cells in the NP. Moreover, our in vivo experiments revealed that transplantation of CD24-positive NP cells enables the recovery of degenerate discs, as evidenced by increased disc height, restored magnetic resonance imaging T2-weighted signal intensity, and NP structure. In terms of the mechanism, HIF-1α–Notch1 pathway activation was essential for the maintenance of CD24-positive NP cells.ConclusionOur studies identify that CD24-positive NP cells are the resident progenitor/notochordal cells in disc regeneration and elucidate a crucial role of HIF-1α–Notch1 pathway in the phenotypic maintenance of CD24-positive NP cells.

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“…Since, the exact cell types present in the NP is debatable and markers which exclusively identify NP cells are not known, particularly in human IVDs, presence of chondrogenic markers alone does not necessarily implicate the differentiation of MSCs into NP lineage. This prompted us to further evaluation of transcription and translation of FOXF1 and KRT19, which have been putatively used as human NP specific markers (Han et al ., ; Rodrigues‐Pinto et al ., ). No other study has investigated NP marker expression upon transplantation of human cells in DDD animal models.…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord derivatives regenerate intervertebral disc

Beeravolu

Brougham

Khan

et al. 2017

J Tissue Eng Regen Med

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Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP), which is a common cause for lower back pain. Although, currently, there is no cure for the degenerative disc disease, stem cell therapy is increasingly being considered for its treatment. In this study, we investigated the feasibility and efficacy of human umbilical cord mesenchymal stem cells (MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate damaged IVD in a rabbit model. Transplanted cells survived, engrafted and dispersed into NP in situ. Significant improvement in the histology, cellularity, extracellular matrix proteins, and water and glycosaminoglycan contents in IVD recipients of CPCs was observed compared to MSCs. In addition, IVDs receiving CPCs exhibited higher expression of NP-specific human markers, SOX9, aggrecan, collagen 2, FOXF1 and KRT19. The novelty of the study is that in vitro differentiated CPCs derived from umbilical cord MSCs, demonstrated far greater capacity to regenerate damaged IVDs, which provides basis and impetus for stem cell based clinical studies to treat degenerative disc disease.

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Differentiation of Human Ligamentum Flavum Stem Cells Toward Nucleus Pulposus-Like Cells Induced by Coculture System and Hypoxia

Cited by 17 publications

References 35 publications

Potential of Human Nucleus Pulposus-Like Cells Derived From Umbilical Cord to Treat Degenerative Disc Disease

Potential of Human Nucleus Pulposus-Like Cells Derived From Umbilical Cord to Treat Degenerative Disc Disease

CD24 identifies nucleus pulposus progenitors/notochordal cells for disc regeneration

Human umbilical cord derivatives regenerate intervertebral disc

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