Isolation and Characterization of Mesenchymal Stromal Cells From Human Degenerated Nucleus Pulposus

Blanco, Juan F.; Graciani, Ignacio F.; Sánchez‐Guijo, Fermín; Muntión, Sandra; Hernández-Campo, Pilar; Santamaría, Carlos; Carrancio, Soraya; Barbado, M.V.; Cruz, Graciela; Gutierrez-Cosio, Silvia; Herrero, Carmen; Miguel, Jesús F. San; Briñón, Jesús G.; Cañizo, María-Consuelo del

doi:10.1097/brs.0b013e3181cb8828

Cited by 179 publications

(159 citation statements)

References 26 publications

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“…The chemotactic ability of BMP-13 could help in the recruitment of host NP cells into tissue engineered scaffolds for the proper integration in to the implant. 28 However, with the knowledge that stem cells may also exist within the disc, [29][30][31] further analysis to determine whether the migratory cells we observed 8 were actual NP cells or were stem cells residing within the NP tissue needs to be delineated. It is also interesting to note a recent finding that BMP-13 can induce the differentiation of stem cells to a nucleus pulposus phenotype.…”

Section: Bmp-13 In Human Intervertebral Discmentioning

confidence: 98%

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

Gulati

Chung

Wei

et al. 2015

Journal Orthopaedic Research

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Our laboratory has demonstrated that bone morphogenetic protein 13 prevented the effects of annular injury in an ovine model, maintaining intervertebral disc height, cell numbers and increasing extracellular matrix production compared to degenerated controls. The present study sought to examine the molecular effects of bone morphogenetic protein 13 on human degenerated disc cells and localize its expression in both human degenerate and scoliotic disc tissue. Effect of bone morphogenetic protein 13 on human derived nucleus pulposus, annulus fibrosus and endplate cells cultured in alginate beads was evaluated by changes in proteoglycan and collagen content. Migratory potential of disc cells towards bone morphogenetic protein 13 was also examined. Bone morphogenetic protein 13 induced significant proteoglycan accumulation in nucleus (18%), annulus (21%) and endplate (23%) cells cultured in alginate beads (p < 0.05) compared to controls. Further bone morphogenetic protein 13 increased collagen I and II protein expression in nucleus and endplate cells. Nucleus cells displayed a significant chemotactic response towards bone morphogenetic protein 13. The endogenous expression of bone morphogenetic protein 13 in degenerate disc tissue was not different to scoliotic disc. Bone morphogenetic protein 13 has the potential to enhance extracellular matrix accumulation and induce cell migration in certain disc cells. Keywords: bone morphogenetic protein 13; human intervertebral disc; low back pain; cell migration; intervertebral disc degeneration Chronic low back pain is strongly associated with intervertebral disc (IVD) degeneration. IVD consists of a central gelatinous nucleus pulposus (NP), surrounded circumferentially by annulus fibrosus (AF) and separated from the vertebral bodies by cartilaginous endplates (EPs). During IVD degeneration, cellular viability is decreased and the gel-like composition of NP becomes fibrous. Additionally, there is increasing irregularity and bifurcation of the lamellar structure of AF. 1Biological therapies aim to retard IVD degeneration and re-establish its biological function by restoring cellular viability and extracellular matrix (ECM). Growth factors such as bone morphogenetic proteins (BMPs), members of transforming growth factor beta (TGF-b) superfamily, play a critical role in stimulation of ECM formation and maintenance of cell numbers. The effect of BMPs on degenerate IVDs in vitro and in vivo has been extensively studied, 2 however, the role of BMP-13 in disc regeneration has not been explored. BMP-13, the human homologue of murine growth and differentiation factor 6, 3 has been highly associated with the stimulation of ECM production. BMP-13 induced aggrecan gene expression and proteoglycan (PG) synthesis in mouse mesenchymal cell line 4 and human articular chondrocytes.5 BMP-13 also stimulated gene expression of collagen II in mouse mesenchymal cell line 4 and collagen synthesis in juvenile bovine articular cartilage explants. 6 Moreover, Zhang et al.have demonstrated t...

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Section: Bmp-13 In Human Intervertebral Discmentioning

confidence: 98%

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

Gulati

Chung

Wei

et al. 2015

Journal Orthopaedic Research

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“…The identification of tissue-specific mesenchymal stem cells (MSCs) in tissues other than the bone marrow, adipose tissue and umbilical cord, has prompted researchers to investigate their presence within the IVD. Using a panel of markers validated by the International Society for Cell Therapy as bone marrow MSC markers (CD90?, CD73?, CD105?, CD166?, CD45-, CD34-, CD14-, HLA-DR-), Risbud and colleagues [65] identified cells within human degenerate discs, that were capable of undergoing differentiation along the chondro-, osteo-and adipogenic lineages, while Blanco and colleagues [66] identified cells capable of chondro and osteogenic differentiation. Using BrdU labelling, Henriksson and colleagues [67] located in vivo a population of progenitor cells in the AF border that showed proliferation in a stem cell niche-like pattern.…”

Section: T (Brachyury) Ratmentioning

confidence: 99%

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

2014

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Cell-based regenerative medicine therapies have been proposed for repairing the degenerated intervertebral disc (a major cause of back pain). However, for this approach to be successful, it is essential to characterise the phenotype of its native cells to guarantee that implanted cells differentiate and maintain the correct phenotype to ensure appropriate cell and tissue function. While recent studies have increased our knowledge of the human nucleus pulposus (NP) cell phenotype, their ontogeny is still unclear. The expression of notochordal markers by a subpopulation of adult NP cells suggests that, contrary to previous reports, notochord-derived cells are retained in the adult NP, possibly coexisting with a second population of cells originating from the annulus fibrosus or endplate. It is not known, however, how these two cell populations interact and their specific role(s) in disc homeostasis and disease. In particular, notochordal cells are proposed to display both anabolic and protective roles; therefore, they may be the ideal cells to repair the degenerate disc. Thus, understanding the ontogeny of the adult NP cells is paramount, as it will inform the medical and scientific communities as to the ideal phenotype to implant into the degenerate disc and the specific pathways involved in stem cell differentiation towards such a phenotype.

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“…MSCs are capable of homing to injured or degenerated tissues where they exert therapeutic effects by providing cytokines and chemokines and enhancing both proliferation and differentiation of resident stem cells [12]. MSCs in human degenerate IVD tissues were first discovered by Risbud in 2007; since that time, a series of attempts have been made to characterize these cells [34][35][36][37]. IVD-derived MSCs exhibit biological characteristics similar to those of BM-MSCs [34].…”

Section: Discussionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor Inhibits the Migration of Cartilage End Plate-Derived Stem Cells by Reacting CD74

Xiong

Huang

Zhou

et al. 2014

Global Spine Journal

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Background: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that regulates inflammatory reactions and the pathophysiology of many inflammatory diseases. Intervertebral disc (IVD) degeneration is characterized by an inflammatory reaction, but the potential role of MIF in IVD degeneration has not been determined. Recent studies have shown that MIF and its receptor, CD74, are involved in regulating the migration of human mesenchymal stem cells (MSCs); Thus, MIF might impair the ability of mesenchymal stem cells (MSCs) to home to injured tissues. Our previous studies indicated that cartilage endplate (CEP)-derived stem cells (CESCs) as a type of MSCs exist in human degenerate IVDs. Here, we investigate the role of MIF in regulating the migration of CESCs.

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Isolation and Characterization of Mesenchymal Stromal Cells From Human Degenerated Nucleus Pulposus

Cited by 179 publications

References 26 publications

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

Macrophage Migration Inhibitory Factor Inhibits the Migration of Cartilage End Plate-Derived Stem Cells by Reacting CD74

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