Angiopellosis as an Alternative Mechanism of Cell Extravasation.

Stem cells possess the ability to home in and travel to damaged tissue when injected intravenously. For the cells to exert their therapeutic effect, they must cross the blood vessel wall and enter the surrounding tissues. The mechanism of extravasation injected stem cells employ for exit has yet to be characterized. Using intravital microscopy and a transgenic zebrafish line Tg(fli1a:egpf) with GFP-expressing vasculature, we documented the detailed extravasation processes in vivo for injected stem cells in comparison to white blood cells (WBCs). While WBCs left the blood vessels by the standard diapedesis process, injected cardiac and mesenchymal stem cells underwent a distinct method of extravasation that was markedly different from diapedesis. Here, the vascular wall undergoes an extensive remodeling to allow the cell to exit the lumen, while the injected cell remains distinctively passive in activity. We termed this process Angio-pello-sis, which represents an alternative mechanism of cell extravasation to the prevailing theory of diapedesis. Stem Cells 2017;35:170-180 Video Highlight: https://youtu.be/i5EI-ZvhBps.

Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs.

Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs. It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. Methods: We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon. Results: Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. Conclusion: Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.

Evidence favoring a secular reduction in mandibular leeway space.

OBJECTIVE: Researchers have documented secular trends in tooth size among recent generations. This study was a test for a change in mandibular leeway space. MATERIALS AND METHODS: Dental casts from participants in the Denver Growth Study (23 boys, 22 girls; born in the 1930s) were compared with casts from a contemporary series of orthodontic patients (23 boys, 22 girls; born in the 1990s). All were phenotypically normal, healthy American whites. RESULTS: Analysis of variance (accounting for sex) showed that the cumulative mandibular primary canine plus first and second primary molar size (c + m1 + m2) was slightly larger in the recent cohort (23.53 mm earlier vs 23.83 mm recent cohort; mean difference: 0.30 mm; P = .009), principally due to larger second primary molars (m2) in the recent cohort. In turn, the sum of the permanent canine and two premolars (C + P1 + P2) was significantly larger in the recent cohort (21.08 mm earlier vs 21.80 mm recent cohort; mean difference: 0.72 mm; P = .002). Larger teeth in the contemporary series produced a mean leeway space per quadrant of 2.03 mm versus 2.45 mm in the earlier cohort-a clinically and statistically significant reduction (P = .030). Some tooth types (primary second molar and permanent canine) were significantly larger in boys than in girls, but the sex difference in leeway space was not statistically significant. CONCLUSION: Results suggest that mandibular leeway space is decreasing in 21st century American whites and may present a challenge to orthodontists in managing tooth size-arch length discrepancies.

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart.

Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the "paint" material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI.