Identification of fibronectin as a major factor in human serum to recruit subchondral mesenchymal progenitor cells

Kulawig, Rebecca; Krüger, Jan Philipp; Klein, Oliver; Konthur, Zoltán; Schütte, H. R.; Klose, Joachim; Kaps, Christian; Endres, Michaela

doi:10.1016/j.biocel.2013.04.016

Cited by 15 publications

(16 citation statements)

References 61 publications

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“…Second, we chose to use hAMSCs instead of other types of stem cells, including neural and bone marrow‐derived stem cells, because hAMSCs are considered easier to obtain, more genetically and morphologically stable in long‐term culture, have a lower senescence ratio, and have a greater proliferative capacity than other stem cell types. Therefore, the findings of the present study might not be applicable to other stem cell types [15, 18]. Moreover, our work focused on brain cancer targeting, and future studies should evaluate whether these findings are also applicable to other neurological pathologies, including stroke, demyelinating diseases such as multiple sclerosis, and neurodegenerative conditions, such as Parkinson's disease.…”

Section: Discussionmentioning

confidence: 90%

“…Differentiation assays were performed to determine the differentiation capacities of hAMSCs, as previously described [18, 15]. In brief, the cells were seeded into 24‐well plates (42,000 cells per well for adipogenic differentiation, 8,400 cells per well for osteogenic differentiation) or cultured as pellets (2.5 × 10 5 cells per tube for chondrogenic differentiation).…”

Section: Methodsmentioning

confidence: 99%

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Pre-Exposure of Human Adipose Mesenchymal Stem Cells to Soluble Factors Enhances Their Homing to Brain Cancer

Smith

Chaichana

Lee

et al. 2015

Stem Cells Translational Medicine

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Recent research advances have established mesenchymal stem cells (MSCs) as a promising vehicle for therapeutic delivery. Their intrinsic tropism for brain injury and brain tumors, their lack of immunogenicity, and their ability to breach the blood-brain barrier make these cells an attractive potential treatment of brain disorders, including brain cancer. Despite these advantages, the efficiency of MSC homing to the brain has been limited in commonly used protocols, hindering the feasibility of such therapies. In the present study, we report a reproducible, comprehensive, cell culture-based approach to enhance human adipose-derived MSC (hAMSC) engraftment to brain tumors. We used micro- and nanotechnological tools to systematically model several steps in the putative homing process. By pre-exposing hAMSCs to glioma-conditioned media and the extracellular matrix proteins fibronectin and laminin, we achieved significant enhancements of the individual homing steps in vitro. This homing was confirmed in an in vivo rodent model of brain cancer. This comprehensive, cell-conditioning approach provides a novel method to enhance stem cell homing to gliomas and, potentially, other neurological disorders.

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Section: Discussionmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Pre-Exposure of Human Adipose Mesenchymal Stem Cells to Soluble Factors Enhances Their Homing to Brain Cancer

Smith

Chaichana

Lee

et al. 2015

Stem Cells Translational Medicine

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“…In human serum, a concentration of 315 μg/ml plasma fibronectin (pFN) was measured in a pool of 10 healthy donors. Chondrocyte migration was determined in the presence of 1–30 μg/ml pFN because this range of concentration showed a migratory effect in mesenchymal progenitor cells before (Kalkreuth et al, ; Kulawig et al, ). Furthermore, a comparison between pFN and rFN showed that both significantly increased the migration of chondrocytes with maximal migration indices of 10.5 and 8.4, respectively, from 1 to 15 μg/ml (Figure a).…”

Section: Resultsmentioning

confidence: 99%

“…In previous work, we demonstrated that pFN is one factor in human serum that stimulates the migration of human mesenchymal progenitor cells (hMPC) (Kulawig et al, ). In this study, the migration of human chondrocytes could be induced at concentrations between 1 and 30 μg/ml pFN, which is in the same range as shown for hMPC (Kalkreuth et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Plasma FN (pFN) as an initial factor plays a crucial role in wound healing because it binds to fibrinogen and induces cell migration mostly via its interaction with integrin α 5 β 1 (Lenselink, ). In past studies, we were able to determine FN as one of the key components in human serum that induced migration as well as proliferation of human mesenchymal progenitor cells (hMPCs) (Kalkreuth et al, ; Kulawig et al, ). The potential of FN to directly induce migration was shown for several cell types such as basal carcinoma cells (Kuonen et al, ), enteric neural crest cells (Nishida, et al, ), and fibroblasts (Missirlis, Haraszti, Kessler, & Spatz, ).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of plasma fibronectin for migration, proliferation, and differentiation on human articular chondrocytes

Krüger

Hondke

Lau

et al. 2019

J Tissue Eng Regen Med

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Plasma fibronectin (pFN) plays a crucial role in wound healing by binding to integrins and inducing cell migration. It is known to induce the migration and proliferation of mesenchymal progenitor cells in vitro, which play a key role during microfracture in cartilage repair. Endogenous chondrocytes from the native cartilage of the defect rim might aid in cartilage repair. In this study, the effect of pFN on proliferation, migration, and differentiation was tested on human articular chondrocytes. Results showed that treatment with pFN increased the migration of chondrocytes in a range of 1-30 μg/ml as tested with no effect on proliferation. TGFβ3-induced chondrogenesis was not affected by pFN. Especially, gene expression of matrix metalloproteinases was not increased by pFN. Plasma FN fragmentation due to storage conditions could be excluded by SDS-PAGE. Moreover, bioactivity of pFN did not alter during storage at 4°C and 40°C for up to 14 days. Taken together, pFN induces the migration but not proliferation of human articular chondrocytes with no inhibitory effect on chondrogenic differentiation. Additionally, no loss of activity or fragmentation of pFN was observed after lyophilization and storage, making pFN an interesting bioactive factor for chondrocyte recruitment.

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Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration

Dirckx

Hul²,

Maes³

2013

Birth Defects Research Pt C

168

134

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During endochondral bone development, bone-forming osteoblasts have to colonize the regions of cartilage that will be replaced by bone. In adulthood, bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, as a prerequisite for skeletal health. A failure of osteoblasts to reach the sites in need of bone formation may contribute to impaired fracture repair. Conversely, stimulation of osteogenic cell recruitment may be a promising osteo-anabolic strategy to improve bone formation in low bone mass disorders such as osteoporosis and in bone regeneration applications. Yet, still relatively little is known about the cellular and molecular mechanisms controlling osteogenic cell recruitment to sites of bone formation. In vitro, several secreted growth factors have been shown to induce osteogenic cell migration. Recent studies have started to shed light on the role of such chemotactic signals in the regulation of osteoblast recruitment during bone remodeling. Moreover, trafficking of osteogenic cells during endochondral bone development and repair was visualized in vivo by lineage tracing, revealing that the capacity of osteoblast lineage cells to move into new bone centers is largely confined to undifferentiated osteoprogenitors, and coupled to angiogenic invasion of the bone-modeling cartilage intermediate. It is well known that the presence of blood vessels is absolutely required for bone formation, and that a close spatial and temporal relationship exists between osteogenesis and angiogenesis. Studies using genetically modified mouse models have identified some of the molecular constituents of this osteogenic-angiogenic coupling. This article reviews the current knowledge on the process of osteoblast lineage cell recruitment to sites of active bone formation in skeletal development, remodeling, and repair, considering the role of chemo-attractants for osteogenic cells and the interplay between osteogenesis and angiogenesis in the control of bone formation.

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Identification of fibronectin as a major factor in human serum to recruit subchondral mesenchymal progenitor cells

Cited by 15 publications

References 61 publications

Pre-Exposure of Human Adipose Mesenchymal Stem Cells to Soluble Factors Enhances Their Homing to Brain Cancer

Pre-Exposure of Human Adipose Mesenchymal Stem Cells to Soluble Factors Enhances Their Homing to Brain Cancer

Characterization of plasma fibronectin for migration, proliferation, and differentiation on human articular chondrocytes

Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration

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