Subhan, B. S. | Search bioRxiv

bioRxiv2024

Functional high capacity exosome-encapsulating bioinspired hydrogel promotes microvascularbed expansion in diabetic mice

Chronic wounds present a significant clinical challenge due to impaired skin microvasculature, particularly in diabetes. The tissue engineering study introduces therapeutic Exo-Q, a unique thermoresponsive polymer hydrogel created with Q protein nanofibers and cultured human bone marrow multipotent stromal cell exosomes with consistent gene signature. Limited, local and topical application of Exo-Q hydrogel is feasible for maximum neovascularization during murine diabetic wound closure in a xenotransplantation model, as well as compatibility and vascular delivery in human skin in a xenograft model. Exo-Q hydrogel treatment significantly reduces diabetic wound closure time within ranges of non-diabetic wounds. This innovative, non-invasive tissue engineered therapeutic option offers a promising approach to addressing the complex pathologies of non-healing wounds.

bioengineering↗

bioRxiv2024

Integrin-deficient T cell leukemia accumulates in the central nervous system

T-cell acute lymphoblastic leukemia (T-ALL) spreads aggressively to the central nervous system (CNS), particularly the leptomeninges. Children with T-ALL are treated with high-dose, CNS-directed chemotherapy, which can cause lasting neurotoxicity and is not always effective. Little is known about how T-ALL enters and persists within the CNS. However, normal T cell migration into the CNS has been extensively studied. Two integrins--VLA-4 and LFA-1--mediate normal T cell entry to the CNS, and VLA-4 blockade effectively treats multiple sclerosis by excluding T cells from the brain. We hypothesized that these integrins would likewise be required for T-ALL CNS entry. Unexpectedly, not only were VLA-4 and LFA-1 dispensable for T-ALL to reach the CNS, integrin-deficient T-ALL accumulated in the CNS compared to control. Mechanistically, integrin loss accelerated T-ALL proliferation in the CNS, suggesting that integrin-mediated interactions may promote quiescence in this space. Integrin blockade synergized with chemotherapy targeting proliferating cells, raising the possibility that combination therapy might be a powerful strategy.

immunology↗