Heterotypic Multicellular Spheroids as Experimental and Preclinical Models of Sprouting Angiogenesis

Sprouting angiogenesis is the common response of live tissues to physiological and pathological angiogenic stimuli. Its accurate evaluation is of utmost importance for basic research and practical medicine and pharmacology and requires adequate experimental models. A variety of assays for angiogenesis were developed, none of them perfect. In vitro approaches are generally less physiologically relevant due to the omission of essential components regulating the process. However, only in vitro models can be entirely non-xenogeneic. The limitations of the in vitro angiogenesis assays can be partially overcome using 3D models mimicking tissue O2 and nutrient gradients, the influence of the extracellular matrix (ECM), and enabling cell-cell interactions. Here we present a review of the existing models of sprouting angiogenesis that are based on the use of endothelial cells (ECs) co-cultured with perivascular or other stromal cells. This approach provides an excellent in vitro platform for further decoding of the cellular and molecular mechanisms of sprouting angiogenesis under conditions close to the in vivo conditions, as well as for preclinical drug testing and preclinical research in tissue engineering and regenerative medicine

Cosmological Fast Optical Transients with the Zwicky Transient Facility: A Search for Dirty Fireballs

International audienceDirty fireballs are a hypothesized class of relativistic massive-star explosions with an initial Lorentz factor $\Gamma_\mathrm{init}$ below the $\Gamma_\mathrm{init}\sim100$ required to produce a long-duration gamma-ray burst (LGRB), but which could still produce optical emission resembling LGRB afterglows. Here we present the results of a search for on-axis optical afterglows using the Zwicky Transient Facility (ZTF). Our search yielded seven optical transients that resemble on-axis LGRB afterglows in terms of their red colors ($g-r>0$ mag), faint host galaxy ($r>23$ mag), and rapid fading ($dr/dt>1$ mag/day). Spectroscopy of the transient emission within a few days of discovery established cosmological distances ($z=0.876$ to $z=2.9$) for six events, tripling the number of afterglows with redshift measurements discovered by optical surveys without a $\gamma$-ray trigger. Upon a retrospective search, four events (ZTF20abbiixp/AT2020kym, ZTF21aagwbjr/AT2021buv, ZTF21aakruew/AT2021cwd, ZTF21abfmpwn/AT2021qbd) turned out to have a likely associated LGRB (GRB200524A, GRB210204A, GRB210212B, GRB210610B), while three did not (ZTF20aajnksq/AT2020blt, ZTF21aaeyldq/AT2021any, ZTF21aayokph/AT2021lfa). Our search revealed no definitive new class of events: the simplest explanation for the apparently "orphan" events is that they were regular LGRBs missed by high-energy satellites due to detector sensitivity and duty cycle, although it is possible that they were intrinsically faint in $\gamma$-rays or viewed slightly off-axis. We rule out a scenario in which dirty fireballs have a similar energy per solid angle to LGRBs and are an order of magnitude more common. In addition, we set the first direct constraint on the ratio of the opening angles of the material producing $\gamma$-rays and the material producing early optical afterglow emission, finding that they must be comparable