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  1. Article ; Online: Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting.

    Bauza, Guillermo / Pasto, Anna / Mcculloch, Patrick / Lintner, David / Brozovich, Ava / Niclot, Federica Banche / Khan, Ilyas / Francis, Lewis W / Tasciotti, Ennio / Taraballi, Francesca

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 16610

    Abstract: Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction ... ...

    Abstract Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.
    MeSH term(s) Aggrecans/genetics ; Aggrecans/metabolism ; Cartilage, Articular/cytology ; Cartilage, Articular/physiology ; Cell Culture Techniques/methods ; Cells, Cultured ; Chondrogenesis/genetics ; Chondrogenesis/immunology ; Chondrogenesis/physiology ; Gene Expression/genetics ; Gene Expression Regulation, Developmental/genetics ; Humans ; Leptin/genetics ; Leptin/metabolism ; Osteoarthritis/genetics ; Osteoarthritis/physiopathology ; Osteopontin/genetics ; Osteopontin/metabolism ; Stem Cells/physiology ; Tissue Scaffolds
    Chemical Substances ACAN protein, human ; Aggrecans ; LEP protein, human ; Leptin ; SPP1 protein, human ; Osteopontin (106441-73-0)
    Language English
    Publishing date 2020-10-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-73188-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Biomimetic Scaffolds Modulate the Posttraumatic Inflammatory Response in Articular Cartilage Contributing to Enhanced Neoformation of Cartilaginous Tissue In Vivo.

    Bauza-Mayol, Guillermo / Quintela, Marcos / Brozovich, Ava / Hopson, Michael / Shaikh, Shazad / Cabrera, Fernando / Shi, Aaron / Niclot, Federica Banche / Paradiso, Francesca / Combellack, Emman / Jovic, Tom / Rees, Paul / Tasciotti, Ennio / Francis, Lewis W / Mcculloch, Patrick / Taraballi, Francesca

    Advanced healthcare materials

    2021  Volume 11, Issue 1, Page(s) e2101127

    Abstract: Focal chondral lesions of the knee are the most frequent type of trauma in younger patients and are associated with a high risk of developing early posttraumatic osteoarthritis. The only current clinical solutions include microfracture, osteochondral ... ...

    Abstract Focal chondral lesions of the knee are the most frequent type of trauma in younger patients and are associated with a high risk of developing early posttraumatic osteoarthritis. The only current clinical solutions include microfracture, osteochondral grafting, and autologous chondrocyte implantation. Cartilage tissue engineering based on biomimetic scaffolds has become an appealing strategy to repair cartilage defects. Here, a chondrogenic collagen-chondroitin sulfate scaffold is tested in an orthotopic Lapine in vivo model to understand the beneficial effects of the immunomodulatory biomaterial on the full chondral defect. Using a combination of noninvasive imaging techniques, histological and whole transcriptome analysis, the scaffolds are shown to enhance the formation of cartilaginous tissue and suppression of host cartilage degeneration, while also supporting tissue integration and increased tissue regeneration over a 12 weeks recovery period. The results presented suggest that biomimetic materials could be a clinical solution for cartilage tissue repair, due to their ability to modulate the immune environment in favor of regenerative processes and suppression of cartilage degeneration.
    MeSH term(s) Biomimetics ; Cartilage, Articular ; Chondrocytes ; Chondrogenesis ; Humans ; Tissue Engineering ; Tissue Scaffolds
    Language English
    Publishing date 2021-10-28
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202101127
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects

    Huda, M.S.B / Dovey, T / Wong, S.P / English, P.J / Halford, J / Mcculloch, P / Cleator, J / Martin, B / Cashen, J / Hayden, K / Wilding, J.P.H / Pinkney, J

    International journal of obesity : journal of the International Association for the Study of Obesity. 2009 Mar., v. 33, no. 3

    2009  

    Abstract: Objective: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. Design: A randomized, double-blind, placebo-controlled study. Patients: Nine lean subjects (mean body mass index (BMI) 23.5+/-3 ... ...

    Abstract Objective: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. Design: A randomized, double-blind, placebo-controlled study. Patients: Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m2) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m2) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m2). Interventions: Subjects were infused with either intravenous ghrelin (5 pmol kg-1 min-1) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. Main outcome measures: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. Results: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001). Conclusions: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.
    Keywords ghrelin ; obesity ; energy expenditure ; appetite ; stomach ; patients ; surgery ; hunger ; respiratory quotient ; body weight
    Language English
    Dates of publication 2009-03
    Size p. 317-325.
    Document type Article
    ZDB-ID 752409-2
    ISSN 1476-5497 ; 0307-0565
    ISSN (online) 1476-5497
    ISSN 0307-0565
    DOI 10.1038/ijo.2008.270
    Database NAL-Catalogue (AGRICOLA)

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