Shahryar Khattak’s research while affiliated with King Abdullah University of Science and Technology and other places

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Publications (1)

Schematic outline of key signaling events regulating (upregulating and downregulating) the efficient differentiation of hPSC derived mature pancreatic islet cells (Left). The reported signaling pathways that are upregulated and downregulated during in vivo mouse pancreatic development are shown along with the corresponding time scale for human pancreas development (Right). Readers are requested to refer to DEVELOPMENTAL DYNAMICS 240:530–565, 2011 and Nature Reviews Drug Discovery volume 20:920–940, 2021 for a detailed diagrammatic model of mouse pancreatic organogenesis Activin/Nodal are growth factors belongs to TGFβ superfamily; LEFTY, Right-left determination factor; CER1, Cerberus; Wnt, Wingless; TGFβ, Transforming Growth Factor β; FGF, Fibroblast Growth Factor; PI3K, Phosphoinositide 3-kinase; JNK/JUN, Jun N-terminal kinase; RA, Retinoic Acid; PKC, Protein kinase C; BMP, bone morphogenic protein; SHH, sonic hedgehog; YAP, yes-associated protein 1; ROCK, Rho-associated protein kinase; Notch, Neurogenic locus notch homolog protein 1; AXL, Tyrosine-protein kinase receptor UFO; E, Embryonic days; dpc, days post coitus; P, postnatal; CS, Carnegie stage; EGF, epidermal growth factor; FGF, fibroblast growth factor
An overall summary of major hPSC derived pancreatic islet like beta cell differentiation protocols in sequential steps that recapitulate in vivo development. We classified the protocols into ‘Before 2014’ and ‘After 2014’ sections based on the significant breakthrough of generating mono hormonal insulin producing β cells after 2014. An overview of all major protocols, organized by their specific stages, time duration, important growth factors and small molecules that were added at each stage and their corresponding year of publication, is presented here S1-S7, Stages from 1–7; hES, human embryonic stem cells; hiPSC, human induced pluripotent stem cells; DE, Definitive Endoderm; PGT, Primitive Gut Tube; PP1/2, Pancreatic Progenitor1/2; PE, Pancreatic Endocrine; EP, Endocrine progenitors; im.β cells, immatured β cells; T1D, Type 1 Diabetes; ND, Non diabetic
Proposed SC-β cell differentiation protocol in comparison with current six stage differentiation protocol. The introduction of new factors and small molecules that could improve the generation of functional pancreatic islet like β cells from hPSCs are shown in red colour (asterisk mark) with their respective stages of the differentiation protocol
A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets
  • Literature Review
  • Full-text available

March 2025

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60 Reads

Stem Cell Research & Therapy

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Leen Azzam

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Taraf Jaro

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Manjula Nandakumar

The search for an effective cell replacement therapy for diabetes has driven the development of “perfect” pancreatic islets from human pluripotent stem cells (hPSCs). These hPSC-derived pancreatic islet-like β cells can overcome the limitations for disease modelling, drug development and transplantation therapies in diabetes. Nevertheless, challenges remain in generating fully functional and mature β cells from hPSCs. This review underscores the significant efforts made by researchers to optimize various differentiation protocols aimed at enhancing the efficiency and quality of hPSC-derived pancreatic islets and proposes methods for their improvement. By emulating the natural developmental processes of pancreatic embryogenesis, specific growth factors, signaling molecules and culture conditions are employed to guide hPSCs towards the formation of mature β cells capable of secreting insulin in response to glucose. However, the efficiency of these protocols varies greatly among different human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) lines. This variability poses a particular challenge for generating patient-specific β cells. Despite recent advancements, the ultimate goal remains to develop a highly efficient directed differentiation protocol that is applicable across all genetic backgrounds of hPSCs. Although progress has been made, further research is required to optimize the protocols and characterization methods that could ensure the safety and efficacy of hPSC-derived pancreatic islets before they can be utilized in clinical settings.

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