Autologous Marrow Mesenchymal Stem Cell Driving Bone Regeneration in a Rabbit Model of Femoral Head Osteonecrosis

Osteonecrosis of the femoral head (ONFH) is a progressive degenerative disease that ultimately requires a total hip replacement. Mesenchymal stromal/stem cells (MSCs), particularly the ones isolated from bone marrow (BM), could be promising tools to restore bone tissue in ONFH. Here, we established a rabbit model to mimic the pathogenic features of human ONFH and to challenge an autologous MSC-based treatment. ON has been originally induced by the synergic combination of surgery and steroid administration. Autologous BM-MSCs were then implanted in the FH, aiming to restore the damaged tissue. Histological analyses confirmed bone formation in the BM-MSC treated rabbit femurs but not in the controls. In addition, the model also allowed investigations on BM-MSCs isolated before (ON-BM-MSCs) and after (ON+BM-MSCs) ON induction to dissect the impact of ON damage on MSC behavior in an affected microenvironment, accounting for those clinical approaches foreseeing MSCs generally isolated from affected patients. BM-MSCs, isolated before and after ON induction, revealed similar growth rates, immunophenotypic profiles, and differentiation abilities regardless of the ON. Our data support the use of ON+BM-MSCs as a promising autologous therapeutic tool to treat ON, paving the way for a more consolidated use into the clinical settings

Human Adipose Mesenchymal Stromal/Stem Cells Improve Fat Transplantation Performance

The resorption rate of autologous fat transfer (AFT) is 40–60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption

Epibiotic pressure contributes to biofouling invader success

Reduced competition is a frequent explanation for the success of many introduced species. In benthic marine biofouling communities, space limitation leads to high rates of overgrowth competition. Some species can utilise other living organisms as substrate (epibiosis), proffering a competitive advantage for the epibiont. Additionally, some species can prevent or reduce epibiotic settlement on their surfaces and avoid being basibionts. To test whether epibiotic pressure differs between native and introduced species, we undertook ex situ experiments comparing bryozoan larval settlement to determine if introduced species demonstrate a greater propensity to settle as epibionts, and a reduced propensity to be basibionts, than native species. Here we report that introduced species opportunistically settle on any space (bare, native, or introduced), whereas native species exhibit a strong tendency to settle on and near other natives, but avoid settling on or near introduced basibionts. In addition, larvae of native species experience greater larval wastage (mortality) than introduced species, both in the presence and absence of living substrates. Introduced species’ ability to settle on natives as epibionts, and in turn avoid epibiosis as basibionts, combined with significantly enhanced native larval wastage, provides a comprehensive suite of competitive advantages contributing to the invasion success of these biofouling species

Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma

Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients

Acyl-homoserine Lactone from <i>Saccharum × officinarum</i> with Stereochemistry-Dependent Growth Regulatory Activity

Acyl-homoserine lactones (AHLs) are a class of compounds produced by Gram-negative bacteria that are used in a process of chemical communication called quorum sensing. Much is known about how bacteria use these chemical compounds to control the expression of important factors; however, there have been few reports about the presence and effects of AHLs in plants. In this study, the phytochemical study of leaves and culms of sugar cane (<i>Saccharum × officinarum</i>) led to the identification of <i>N</i>-(3-oxo-octanoyl)­homoserine lactone. Since the absolute configuration of the natural product could not be determined, both <i>R</i> and <i>S</i> enantiomers of <i>N</i>-(3-oxo-octanoyl)­homoserine lactone were synthesized and tested in sugar cane culms. The enantiomers caused changes in the mass and length of buds and roots when used at micromolar concentrations. Using the sugar cane RB96-6928 variety, the <i>S</i> enantiomer increased sprouting of roots more effectively than the <i>R</i> enantiomer. Furthermore, scanning electron microscopy showed that both the <i>R</i> and <i>S</i> enantiomers led to more stretched root cells compared with the control