Journal: Stem Cells Translational Medicine
Article Title: Toward Precision Medicine with Human Pluripotent Stem Cells for Diabetes
doi: 10.1093/stcltm/szac030
Figure Lengend Snippet: Advances and limitations in generating pancreatic β cells from hPSCs. Multiple modifications in β-cell differentiation protocols are listed, along with limitations in obtaining hPSC-derived β cells representing adult human β cells persist. Use of ROCKII and YAP inhibition, as well as cytoskeletal depolymerizer during endocrine commitment improves proportion and functionality of the generated β cells. Furthermore, physical manipulation such as disassociation and reaggregation of the hPSC-derived endocrine clusters also improves maturity of β cells and eliminates non-β cells, such as α cells, delta cells or non-committed progenitors and polyhormonal cells, that are normally present in differentiated endocrine clusters along with β cells. However, key maturation markers are still absent from the differentiated β cells along with aberrant calcium signaling and dysfunctional mitochondria.
Article Snippet: Furthermore, Vertex pharmaceuticals, running a Phase I/II clinical trial that transplants fully differentiated hPSC-derived β cells, infused into the hepatic portal vein of hypoglycemic patients with T1D, presented first set of results where they showed a 91% decrease in exogenous insulin administration for their first patient within 90 days, thus providing a huge breakthrough in the field of β-cell replacement therapy (NCT04786262).
Techniques: Cell Differentiation, Derivative Assay, Inhibition, Generated