Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells

Ferguson, Elaine Lesley; Naseer, Sameza; Powell, Lydia C.; Hardwicke, Joseph; Young, Fraser; Zhu, Bangfu; Liu, Qian; Song, Bing; Thomas, David W.

doi:10.1016/j.scr.2018.10.008

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…However, all the cells in these articles were unsorted cells, so we cannot rule out stem cell proliferation. In addition, the culture medium in these studies included EGF and FGF2; thus, we cannot exclude the possibility that the increased rates of GSCs after hypoxia exposure may have been induced by EGF and FGF2, not the hypoxic environment, as EGF and FGF2 can promote the proliferation of stem cells [30,31]. Therefore, to make our results more accurate, we combined CD133 [1,32,33] and CD15 [34,35] as stem cell markers due to the controversy regarding the use of CD133 as a stem cell marker [36].…”

Section: Discussionmentioning

confidence: 99%

HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells through Sox2 under hypoxic conditions

Wang¹,

Gong²,

Liao³

et al. 2022

J. Cancer

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Objective: Our previous study showed that glioma stem-like cells could be induced to undergo dedifferentiation under hypoxic conditions, but the mechanism requires further study. HIF1α and HIF2α are the main molecules involved in the response to hypoxia, and Sox2, as a retroelement, plays an important role in the formation of induced pluripotent stem cells, especially in hypoxic microenvironments. Therefore, we performed a series of experiments to verify whether HIF1α, HIF2α and Sox2 regulated glioma cell dedifferentiation under hypoxic conditions. Materials and methods: Sphere formation by single glioma cells was observed, and CD133 and CD15 expression was compared between the normoxic and hypoxic groups. HIF1α, HIF2α, and Sox2 expression was detected using the CGGA database, and the correlation among HIF1α, HIF2α and Sox2 levels was analyzed. We knocked out HIF1α, HIF2α and Sox2 in glioma cells and cultured them under hypoxic conditions to detect CD133 and CD15 expression. The above cells were implanted into mouse brains to analyze tumor volume and survival time. Results: New spheres were formed from single glioma cells in 1% O2, but no spheres were formed in 21% O2. The cells cultured in 1% O2 highly expressed CD133 and CD15 and had a lower apoptosis rate. The CGGA database showed HIF1α and HIF2α expression in glioma. Knocking out HIF1α or HIF2α led to a decrease in CD133 and CD15 expression and inhibited sphere formation under hypoxic conditions. Moreover, tumor volume and weight decreased after HIF1α or HIF2α knockout with the same temozolomide treatment. Sox2 was also highly expressed in glioma, and there was a positive correlation between the HIF1α/HIF2α and Sox2 expression levels. Sox2 was expressed at lower levels after HIF1α or HIF2α was knocked out. Then, Sox2 was knocked out, and we found that CD133 and CD15 expression was decreased. Moreover, a lower sphere formation rate, higher apoptosis rate, lower tumor formation rate and longer survival time after temozolomide treatment were detected in the Sox2 knockout cells. Conclusion:In a hypoxic microenvironment, the HIF1α/HIF2α-Sox2 network induced the formation of glioma stem cells through the dedifferentiation of differentiated glioma cells, thus promoting glioma cell chemoresistance. This study demonstrates that both HIF1α and HIF2α, as genes upstream of Sox2, regulate the malignant progression of glioma through dedifferentiation.

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Section: Discussionmentioning

confidence: 99%

HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells through Sox2 under hypoxic conditions

Wang¹,

Gong²,

Liao³

et al. 2022

J. Cancer

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“…However, on day 14, hiPSC‐PMDs in the TGF‐β1 conjugated GelMA hydrogels concurrently underwent myogenic modulation confirmed by increased MyHC expression, which might result from gradually degraded TGF‐β1 on GelMA chains at 37 °C over time. [ 32 ] hiPSC‐PMDs showed high expression of PDGFR‐α and Tcf4 when cultured in TGF‐β1 conjugated GelMA hydrogels (Figure 5E). On day 7, the cultures showed low expression of fibroblast markers when 1000 ng of TGF‐β1 was used; although, fibroblast markers increased on day 14.…”

Section: Resultsmentioning

confidence: 99%

Engineering Stem Cell Fate Controlling Biomaterials to Develop Muscle Connective Tissue Layered Myofibers

Han,

Lee,

Rodríguez‐delaRosa

et al. 2023

Adv Funct Materials

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Skeletal muscle connective tissue (MCT) surrounds myofiber bundles to provide structural support, produce force transduction from tendons, and regulate satellite cell differentiation during muscle regeneration. Engineered muscle tissue composed of myofibers layered within MCT has not yet been developed. Herein, a bioengineering strategy to create MCT‐layered myofibers through the development of stem cell fate‐controlling biomaterials that achieve both myogenesis and fibroblast differentiation in a locally controlled manner at the single construct is introduced. The reciprocal role of transforming growth factor‐beta 1 (TGF‐β1) and its inhibitor as well as 3D matrix stiffness to achieve co‐differentiation of MCT fibroblasts and myofibers from a human‐induced pluripotent stem cell (hiPSC)‐derived paraxial mesoderm is studied. To avoid myogenic inhibition, TGF‐β1 is conjugated on the gelatin‐based hydrogel to control the fibroblasts’ populations locally; the TGF‐β1 degrades after 2 weeks, resulting in increased MCT‐specific extracellular matrix (ECM) production. The locations of myofibers and fibroblasts are precisely controlled by using photolithography and co‐axial wet spinning techniques, which results in the formation of MCT‐layered functional myofibers in 3D constructs. This advanced engineering strategy is envisioned as a possible method for obtaining biomimetic human muscle grafts for various biomedical applications.

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“…Various types of growth factors (cytokines) can increase stem cell proliferation, migratory capacity, and differentiation potential towards a specific lineage ( Meng et al, 2008 ). In this context, Ferguson et al conjugated epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) with dextrin to support growth and differentiation of mouse neural stem cells via controllable growth factor release ( Ferguson et al, 2018 ). Similarly, Zhao et al synthesized a chitosan hydrogel scaffolds by conjugating C domain peptide of IGF-1 onto chitosan and co-transplanted with human placenta-derived MSCs into a murine hindlimb ischemia model.…”

Section: The Correlation Between the Physical Properties Of Biomateri...mentioning

confidence: 99%

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

Hong

2022

Front. Cell Dev. Biol.

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Stem cell-based therapeutics have gained tremendous attention in recent years due to their wide range of applications in various degenerative diseases, injuries, and other health-related conditions. Therapeutically effective bone marrow stem cells, cord blood- or adipose tissue-derived mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and more recently, induced pluripotent stem cells (iPSCs) have been widely reported in many preclinical and clinical studies with some promising results. However, these stem cell-only transplantation strategies are hindered by the harsh microenvironment, limited cell viability, and poor retention of transplanted cells at the sites of injury. In fact, a number of studies have reported that less than 5% of the transplanted cells are retained at the site of injury on the first day after transplantation, suggesting extremely low (<1%) viability of transplanted cells. In this context, 3D porous or fibrous national polymers (collagen, fibrin, hyaluronic acid, and chitosan)-based scaffold with appropriate mechanical features and biocompatibility can be used to overcome various limitations of stem cell-only transplantation by supporting their adhesion, survival, proliferation, and differentiation as well as providing elegant 3-dimensional (3D) tissue microenvironment. Therefore, stem cell-based tissue engineering using natural or synthetic biomimetics provides novel clinical and therapeutic opportunities for a number of degenerative diseases or tissue injury. Here, we summarized recent studies involving various types of stem cell-based tissue-engineering strategies for different degenerative diseases. We also reviewed recent studies for preclinical and clinical use of stem cell-based scaffolds and various optimization strategies.

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Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells

Cited by 9 publications

References 48 publications

HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells through Sox2 under hypoxic conditions

HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells through Sox2 under hypoxic conditions

Engineering Stem Cell Fate Controlling Biomaterials to Develop Muscle Connective Tissue Layered Myofibers

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

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