Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats

Li, Ge; Li-song, Huang; Jiang, Minghong; Wu, Huiling; Chen, Jing; Yin, Huan; Yan, Siyu; Saiyin, Hexige; Fan, Weiwen; Lu, Zhiqiang; Lu, Daru

doi:10.1038/aps.2010.130

Cited by 10 publications

(3 citation statements)

References 44 publications

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“…Since the VEGF‐heparin combination tested did not reach full saturation at heparin‐binding sites, in future studies, one could use these available sites to bind a second immunomodulatory factor. Untried immunomodulatory agents include JAG‐1, a Notch ligand implicated in Treg generation, the CD200‐CD200R axis, implicated in the activation/effector functions of T cells, interleukin‐2, implicated in upregulation of Foxp3 + Tregs, basic fibroblast growth factor (bFGF), a potent angiogenic factor, and Insulin‐like Growth Factor‐1 (IGF‐1), a survival factor 123–127 . To promote both long‐term graft survival and immune evasion, any combination of these immunomodulatory factors, such as IL‐2 with bFGF, could be investigated.…”

Section: Designing Next‐generation Therapeutic Combinations Holisticallymentioning

confidence: 99%

Combinatorial islet protective therapeutic approaches in β‐cell transplantation: Rationally designed solutions using a target product profile

Brauns

Sluder

et al. 2023

FASEB BioAdvances

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While progress has been made in the development of islet cell transplantation (ICT) as a viable alternative to the use of exogenous insulin therapy in the treatment of type 1 diabetes, it has not yet achieved its full potential in clinical studies. Ideally, ICT would enable lifelong maintenance of euglycemia without the need for exogenous insulin, blood glucose monitoring or systemic immune suppression. To achieve such an optimal result, therapeutic approaches should simultaneously promote long‐term islet viability, functionality, and localized immune protection. In practice, however, these factors are typically tackled individually. Furthermore, while the requirements of optimal ICT are implicitly acknowledged across numerous publications, the literature contains few comprehensive articulations of the target product profile (TPP) for an optimal ICT product, including key characteristics of safety and efficacy. This review aims to provide a novel TPP for ICT and presents promising tried and untried combinatorial approaches that could be used to achieve the target product profile. We also highlight regulatory barriers to the development and adoption of ICT, particularly in the United States, where ICT is only approved for use in academic clinical trials and is not reimbursed by insurance carriers. Overall, this review argues that the clear definition of a TPP in addition to the use of combinatorial approaches could help to overcome the clinical barriers to the widespread adoption of ICT for the treatment of type 1 diabetes.

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Section: Designing Next‐generation Therapeutic Combinations Holisticallymentioning

confidence: 99%

Combinatorial islet protective therapeutic approaches in β‐cell transplantation: Rationally designed solutions using a target product profile

Brauns

Sluder

et al. 2023

FASEB BioAdvances

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“…Furthermore, some novel protocols are proved to be able to promote the functional maturation of transplantation; for example, angiotensin II type 2 receptor is critical for the development of pancreatic endocrine lineage [70]. bFGF-treated rat proliferating islet progenitor cells (PIC) in vitro were ameliorated post-transplantation [71].…”

Section: Preclinical Study: Obstacles Lie Ahead and Strategies Takenmentioning

confidence: 99%

Cell therapy in diabetes: current progress and future prospects

et al. 2015

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“…In the first step of differentiation, transduced hAFSCs were subjected to high levels of activin A to initiate differentiation toward endodermal lineages (D'Amour et al ., 2005). Next, endodermally committed AFSCs were cultured on a coating of poly‐ l ‐ornithine, along with bFGF, which promoted further proliferation (Li et al ., ; Ogneva and Martinova, ; Le Bras et al ., ). Thereafter, nicotinamide was included to induce β ‐cell maturation and enhance insulin production from the resulting clusters (Ye et al ., ).…”

Section: Introductionmentioning

confidence: 98%

Pdx1and controlled culture conditions induced differentiation of human amniotic fluid-derived stem cells to insulin-producing clusters

Chun

Mack

Moorefield

et al. 2012

J Tissue Eng Regen Med

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This study investigated the differentiation of human amniotic fluid-derived stem cells (hAFSCs) into insulin-producing clusters in vitro. Adenovirally-delivered mouse Pdx1 (Ad-Pdx1) induced human Pdx1 expression in hAFSCs and enhanced the coordinated expression of downstream b-cell markers. When Ad-Pdx1-transduced hAFSCs were sequentially treated with activin A, bFGF and nicotinamide and the culture plate surface coated with poly-L-ornithine, the expression of islet-associated human mRNAs for Pdx1, Pax6, Ngn3 and insulin was increased. C-peptide ELISA confirmed that Ad-Pdx1-transduced hAFSCs processed and secreted insulin in a manner consistent with that pathway in pancreatic b-cells. To sustain the b-cell-like phenotype and investigate the effect of three-dimensional (3D) conformation on the differentiation of hAFSCs, Pdx1-transduced cells were encapsulated in alginate and cultured long-term under serum-free conditions. Over 2 weeks, partially differentiated hAFSC clusters increased in size and increased insulin secretion. Taken together, these data demonstrate that ectopic Pdx1 expression initiates pancreatic differentiation in hAFSCs and that a b-cell-like phenotype can be augmented by culture conditions that mimic the stromal components and 3D geometry associated with pancreatic islets.

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Implantation of bFGF-treated islet progenitor cells ameliorates streptozotocin-induced diabetes in rats

Abstract: Implantation of bFGF-treated proliferating islet cells is a promising cellular therapeutic approach for diabetes.

Cited by 10 publications

References 44 publications

Combinatorial islet protective therapeutic approaches in β‐cell transplantation: Rationally designed solutions using a target product profile

Combinatorial islet protective therapeutic approaches in β‐cell transplantation: Rationally designed solutions using a target product profile

Cell therapy in diabetes: current progress and future prospects

Pdx1and controlled culture conditions induced differentiation of human amniotic fluid-derived stem cells to insulin-producing clusters

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