Use of FGF-2 and FGF-18 to direct bone marrow stromal stem cells to chondrogenic and osteogenic lineages

Shu, Cindy; Smith, Susan; Little, Christopher B.; Melrose, James

doi:10.4155/fsoa-2016-0034

Cited by 34 publications

(28 citation statements)

References 65 publications

(72 reference statements)

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“…To prepare cells for injection, frozen aliquots were thawed, cultured to passage 6, and on the day of injection isolated by trypsin digestion, counted, and resuspended in sterile saline (2 × 10 6 cells/ml). Equivalent passage 6 cells were analysed for cell surface markers (CD105, CD29, Sca1, CD45; R&D Systems Mouse MSC Kit FMC003) and tri-lineage differentiation [29].…”

Section: Mouse Msc Isolation Expansion and Characterisationmentioning

confidence: 99%

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

et al. 2020

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Background: Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progression is unclear. Two therapies, hyaluronan (HA) and mesenchymal stem cells (MSCs), have demonstrated efficacy in some clinical settings: HA acting as device to improve joint function and provide pain relief, while MSCs may have immunomodulatory and disease-modifying effects. We used these agents to investigate whether changes in pain sensitization or structural damage were linked to modulation of the synovial inflammatory response in post-traumatic OA. Methods: Skeletally mature C57BL6 male mice underwent medial-meniscal destabilisation (DMM) surgery followed by intra-articular injection of saline, a hyaluronan hexadecylamide derivative (Hymovis), bone marrow-derived stem cells (MSCs), or MSC + Hymovis. We quantified the progression of OA-related cartilage, subchondral bone and synovial histopathology, and associated pain sensitization (tactile allodynia). Synovial lymphocytes, monocyte/ macrophages and their subpopulations were quantified by fluorescent-activated cell sorting (FACS), and the expression of key inflammatory mediators and catabolic enzyme genes quantified by real-time polymerase chain reaction (PCR). Results: MSC but not Hymovis significantly reduced late-stage (12-week post-DMM) cartilage proteoglycan loss and structural damage. Allodynia was initially reduced by both treatments but significantly better at 8 and 12 weeks by Hymovis. Chondroprotection by MSCs was not associated with specific changes in synovial inflammatory cell populations but rather regulation of post-injury synovial Adamts4, Adamts5, Mmp3, and Mmp9 expression. Reduced acute post-injury allodynia with all treatments coincided with decreased synovial macrophage and T cell numbers, while longer-term effect on pain sensitization with Hymovis was associated with increased M2c macrophages. Conclusions: This therapeutic study in mice demonstrated a poor correlation between cartilage, bone or synovium (histo)pathology, and pain sensitization. Changes in the specific synovial inflammatory cell subpopulations may be associated with chronic OA pain sensitization, and a novel target for symptomatic treatment.

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Section: Mouse Msc Isolation Expansion and Characterisationmentioning

confidence: 99%

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

et al. 2020

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“…[419] A sheep OA model has also demonstrated that intra-articular injection of allogeneic adipose derived MSCs combined with www.advancedsciencenews.com www.advtherap.com HA efficiently blocked OA progression and promoted cartilage regeneration. [424,425] This suggests that this step could improve their cartilage repair capabilities if FGF-2/FGF-18 and MSCs were co-administered intra-articularly. [421] Chondrogenic priming of bone marrow stromal MSCs in the laboratory is reported to improve their anabolic ECM gene expression profiles and the development of their ability to undertake cartilaginous repair within cartilage defects in a full thickness cartilage defect model in sheep.…”

Section: Animal Models Of Oa Which Demonstrate the Utility Of Mscsmentioning

confidence: 99%

“…[420] Furthermore, intra-articular injection of allogeneic MSCs with HA in an in vivo anterior cruciate ligament transection rabbit model of OA, the joint surface showed less cartilage loss and surface abrasion after MSC injection compared to tissues receiving HA injection alone thus the MSCs apparently reduced the progression and severity of OA. If MSC differentiation could be manipulated as suggested by the findings of in vitro experiments conducted with these components [425] this would be expected to be beneficial in the treatment of OA. [422] Further studies have shown that chondrogenic pre-conditioning of MSCs enhanced cartilage regeneration through epigenetic methylation modifications of Nanog and Oct4 in committed chondrogenic cell populations suitable for the treatment of OA cartilage lesions.…”

Section: Animal Models Of Oa Which Demonstrate the Utility Of Mscsmentioning

confidence: 99%

“…[423] FGF-2 and FGF-18 have also been used to pre-condition bone marrow derived stromal MSCs promoting cellular proliferation for expansion of MSC numbers and guiding them to appropriate chondrogenic repair phenotypes in vitro. [424,425] This suggests that this step could improve their cartilage repair capabilities if FGF-2/FGF-18 and MSCs were co-administered intra-articularly. This possibility has not been considered as a potential mechanism whereby MSC cell proliferation could be enhanced in-situ and the cartilage repair properties of undifferentiated stem cells could be guided to a reparative phenotype.…”

Section: Animal Models Of Oa Which Demonstrate the Utility Of Mscsmentioning

confidence: 99%

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Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Hayes

Melrose

2019

Advanced Therapeutics

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The aim of this study is to review developments in glycosaminoglycan and proteoglycan research relevant to cartilage repair biology and in particular the treatment of osteoarthritis (OA). Glycosaminoglycans decorate a diverse range of extracellular matrix and cell associated proteoglycans conveying structural organization and physico-chemical properties to tissues. They play key roles mediating cellular interactions with bioactive growth factors, cytokines, and morphogenetic proteins, and structural fibrillar collagens, cell interactive and extracellular matrix proteoglycans, and glycoproteins which define tissue function. Proteoglycan degradation detrimentally affects tissue functional properties. Therapeutic strategies have been developed to counter these degenerative changes. Neo-proteoglycans prepared from chondroitin sulfate or hyaluronan and hyaluronan or collagen-binding peptides emulate the interactive, water imbibing, weight bearing, and surface lubricative properties of native proteoglycans. Many neo-proteoglycans outperform native proteoglycans in terms of water imbibition, matrix stabilization, and resistance to proteolytic degradation. The biospecificity of recombinant proteoglycans however, provides precise attachment to native target molecules. Visco-supplements augmented with growth factors/therapeutic cells, hyaluronan, and lubricin (orthobiologicals) have the capacity to lubricate and protect cartilage, control inflammation, and promote cartilage repair and regeneration of early cartilage lesions and may represent a more effective therapeutic approach to the treatment of mild to moderate OA and deserve further study.Similar protective perineural net structures assembled from the lectican proteoglycan family and HA also occur in the CNS/PNS. These so called perineuronal nets are visualized by immunolocalization of MAb 1B5 (+) epitope in rat brain (e) and pericellular 1B5(+) epitope expression by isolated neurons (f). Scale bars 100 µm.

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“…Shu et al demonstrated that FGF18 promoted early chondrogenesis and delayed hypertrophy during chondrogenic differentiation of isolated mesenchymal stem cells (MSC). However, FGF18 also suppressed chondroanabolic expression and enhanced the expression of osteogenic markers after the initial phase [77]. Therefore, they hypothesized that FGF18 has chondrogenic properties to some extent but is also involved in terminal differentiation of prehypertrophic columnar and hypertrophic growth plate chondrocytes [77].…”

Section: Regulation Of Chondroanabolic Processesmentioning

confidence: 99%

Pathomechanisms of Posttraumatic Osteoarthritis: Chondrocyte Behavior and Fate in a Precarious Environment

Riegger

2020

IJMS

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Traumatic injuries of the knee joint result in a wide variety of pathomechanisms, which contribute to the development of so-called posttraumatic osteoarthritis (PTOA). These pathogenetic processes include oxidative stress, excessive expression of catabolic enzymes, release of damage-associated molecular patterns (DAMPs), and synovial inflammation. The present review focuses on the underlying pathomechanisms of PTOA and in particular the behavior and fate of the surviving chondrocytes, comprising chondrocyte metabolism, regulated cell death, and phenotypical changes comprising hypertrophy and senescence. Moreover, possible therapeutic strategies, such as chondroanabolic stimulation, anti-oxidative and anti-inflammatory treatment, as well as novel therapeutic targets are discussed.

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Use of FGF-2 and FGF-18 to direct bone marrow stromal stem cells to chondrogenic and osteogenic lineages

Cited by 34 publications

References 65 publications

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

Pathomechanisms of Posttraumatic Osteoarthritis: Chondrocyte Behavior and Fate in a Precarious Environment

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