Heilshorn, S. | bioRxiv Science

bioRxiv2022

Biocompatible polymers for scalable production of human neural organoids

The generation of neural organoids from human pluripotent stem cells holds great promise in modeling disease and screenings drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here, we develop a scalable neural organoid platform by screening biocompatible polymers that prevent fusion of organoids cultured in suspension. We show that addition of one inexpensive polysaccharide enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids.

neuroscience↗

bioRxiv2020

Sustained Release of IL-2 Using an Injectable Hydrogel Prevents Autoimmune Diabetes

Interleukin 2 (IL-2) is a promising therapy for autoimmune type 1 diabetes (T1D), but the short half-life in vivo (less than 6 minutes) limits effective tissue exposure to IL-2. Tissue exposure is required for the tolerogenic effects of IL-2. We have developed an injectable hydrogel that incorporates heparin polymers to enable the sustained release of IL-2. This platform uses clinical grade and commercially available materials, including collagen, hyaluronan, and heparin, to deliver IL-2 by slowly degrading and releasing IL-2 over a two-week period in vivo. We find that heparin potentiates the activity of IL-2 and IL-2-mediated expansion of Foxp3+ regulatory T cell (Treg). Hydrogel-mediated IL-2 release showed a reduction of CD4+ and CD8+ T cells and an increase of FoxP3+ Treg in the lymph nodes of injected mice. Moreover, in the Non-Obese Diabetic (NOD) mouse model of T1D once-weekly administration of IL-2 hydrogels prevented diabetes onset as efficiently as 3x weekly repeated injections of soluble IL-2. Together these data suggest that heparin-containing hydrogels may have benefit in delivering low-dose IL-2 and promoting immune tolerance in autoimmune diabetes.

immunology↗