AI Article Synopsis
- Advances in treating β cell loss focus on therapies that either replace islet cells or enhance cell growth in type 1 and type 2 diabetes.
- The study proposes creating prodrugs that activate in high-zinc environments, which β cells naturally have, interacting with simple cell cultures that don't accurately reflect real conditions.
- They developed a Disque Platform (DP) that combines the best features of 2D and 3D cultures, leading to the discovery of a promising compound that boosts β cell proliferation by 2.4 times compared to the current standard, harmine.
Article Abstract
Advances in treating β cell loss include islet replacement therapies or increasing cell proliferation rate in type 1 and type 2 diabetes, respectively. We propose developing multiple proliferation-inducing prodrugs that target high concentration of zinc ions in β cells. Unfortunately, typical two-dimensional (2D) cell cultures do not mimic in vivo conditions, displaying a markedly lowered zinc content, while 3D culture systems are laborious and expensive. Therefore, we developed the Disque Platform (DP)-a high-fidelity culture system where stem cell-derived β cells are reaggregated into thin, 3D discs within 2D 96-well plates. We validated the DP against standard 2D and 3D cultures and interrogated our zinc-activated prodrugs, which release their cargo upon zinc chelation-so preferentially in β cells. Through developing a reliable screening platform that bridges the advantages of 2D and 3D culture systems, we identified an effective hit that exhibits 2.4-fold increase in β cell proliferation compared to harmine.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673808 | PMC |
| http://dx.doi.org/10.1126/sciadv.abc3207 | DOI Listing |
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