Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)
Published: Jan. 20, 2024
Stem cell-derived pancreatic progenitors (SC-PPs), as an unlimited source of SC-derived β (SC-β) cells, offers a robust tool for diabetes treatment in stem cell-based transplantation, disease modeling, and drug screening. Whereas, PDX1
Language: Английский
Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)
Published: June 6, 2023
The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, is currently limited by the substantial line-to-line batch-to-batch variabilities, which severely impede progress scientific research manufacturing products. For instance, PSC-to-cardiomyocyte (CM) vulnerable inappropriate doses CHIR99021 (CHIR) that are applied in initial stage mesoderm differentiation. Here, harnessing live-cell bright-field imaging machine learning (ML), we realize real-time recognition entire process, e.g., CMs, cardiac progenitor (CPCs), PSC clones, even misdifferentiated cells. This enables non-invasive prediction efficiency, purification ML-recognized CMs CPCs for reducing contamination, early assessment CHIR dose correcting misdifferentiation trajectory, evaluation colonies controlling start point differentiation, all provide more invulnerable method with resistance variability. Moreover, established ML models as readout chemical screen, identify CDK8 inhibitor can further improve overdose CHIR. Together, this study indicates artificial intelligence able guide iteratively optimize achieve consistently high efficiency across lines batches, providing better understanding rational modulation process biomedical applications.
Language: Английский
Citations
14
Metabolism, Journal Year: 2024, Volume and Issue: 152, P. 155786 - 155786
Published: Jan. 10, 2024
Diabetes presents a pressing healthcare crisis, necessitating innovative solutions. Organoid technologies have rapidly advanced, leading to the emergence of bioengineering islet organoids as an unlimited source insulin-producing cells for treating insulin-dependent diabetes. This advancement surpasses need cadaveric transplantation. However, clinical translation this approach faces two major limitations: immature endocrine function and absence perfusable vasculature compared primary human islets. In review, we summarize latest developments in functional vitro promoting vascularization organoid grafts before after We highlight crucial roles ensuring long-term survival, maturation, functionality organoids. Additionally, discuss key considerations that must be addressed organoid-based therapy, including immaturity, undesired heterogeneity, potential tumorigenic risks.
Language: Английский
Citations
6
Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 207, P. 115205 - 115205
Published: Feb. 13, 2024
Language: Английский
Citations
6
Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15
Published: June 20, 2024
Diabetes mellitus (DM), is a chronic disorder characterized by impaired glucose homeostasis that results from the loss or dysfunction of pancreatic β-cells leading to type 1 diabetes (T1DM) and 2 (T2DM), respectively. Pancreatic rely great degree on their endoplasmic reticulum (ER) overcome increased secretary need for insulin biosynthesis secretion in response nutrient demand maintain body. As result, are potentially under ER stress following levels rise circulation proper pro-insulin folding mediated unfolded protein (UPR), underscoring importance this process normal β-cell function. However, excessive prolonged influx nascent proinsulin into lumen can exceed capacity subsequently dysfunction. In mammalian cells, such as β-cells, primarily regulated three canonical ER-resident transmembrane proteins: ATF6, IRE1, PERK/PEK. Each these proteins generates transcription factor (ATF4, XBP1s, respectively), which turn activates stress-inducible genes. An increasing number evidence suggests unresolved dysregulated signaling pathways play pivotal role failure defect diabetes. article we first highlight summarize recent insights its associated mechanisms function second how could be targeted vitro during direct differentiation protocols generation hPSC-derived faithfully phenocopy all features bona fide human therapy drug screening.
Language: Английский
Citations
6
Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)
Published: Jan. 20, 2024
Stem cell-derived pancreatic progenitors (SC-PPs), as an unlimited source of SC-derived β (SC-β) cells, offers a robust tool for diabetes treatment in stem cell-based transplantation, disease modeling, and drug screening. Whereas, PDX1
Language: Английский
Citations
5