Strategy for constructing vascularized adipose units in poly(l-glutamic acid) hydrogel porous scaffold through inducing in-situ formation of ASCs spheroids

Zhang, Kunxi; Li, Song; Jia, Wang; Yan, Shifeng; Li, Guifei; Cui, Lei; Yin, Jingbo

doi:10.1016/j.actbio.2017.01.043

Cited by 72 publications

(52 citation statements)

References 37 publications

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“…However, these strategies fail to create microtissues that mirror both the functional (adiponectin secretion, environmental sensitivity) and histological characteristics (large, unilocular lipid droplet accumulation) of native adipose tissue. Notably most efforts to date have utilized either immature adipose derived stem cells 39 , 41 , 42 , pre-adipocytes 40 , or 3T3-L1 mouse pre-adipocytes 43 possibly contributing to the lack of unilocular lipid droplet morphology typically seen in mature adipocytes in vivo . To date, the closest generation of a 3D adipose microtissue has come from entrapping mature adipocytes within a scaffold.…”

Section: Discussionmentioning

confidence: 99%

Scaffold-free generation of uniform adipose spheroids for metabolism research and drug discovery

Klingelhutz

Gourronc

Chaly

et al. 2018

Sci Rep

110

107

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Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D culture often does not reflect the complexity of fat tissue. Animal models are also problematic in that they are expensive, time consuming, and may not completely recapitulate human biology because of species variation. To address these problems, we have developed a scaffold-free method to generate 3D adipose spheroids from primary or immortal human or mouse pre-adipocytes. Pre-adipocytes self-organize into spheroids in hanging drops and upon transfer to low attachment plates, can be maintained in long-term cultures. Upon exposure to differentiation cues, the cells mature into adipocytes, accumulating large lipid droplets that expand with time. The 3D spheroids express and secrete higher levels of adiponectin compared to 2D culture and respond to stress, either culture-related or toxin-associated, by secreting pro-inflammatory adipokines. In addition, 3D spheroids derived from brown adipose tissue (BAT) retain expression of BAT markers better than 2D cultures derived from the same tissue. Thus, this model can be used to study both the maturation of pre-adipocytes or the function of mature adipocytes in a 3D culture environment.

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Section: Discussionmentioning

confidence: 99%

Scaffold-free generation of uniform adipose spheroids for metabolism research and drug discovery

Klingelhutz

Gourronc

Chaly

et al. 2018

Sci Rep

110

107

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“… 39 Although adipogenesis is promoted in softer hydrogels, MSCs in them usually need to be in very high densities, which could be the reason our hydrogels did not show LPL expression. 40 , 41 …”

Section: Discussionmentioning

confidence: 99%

Hybrid Protein–Glycosaminoglycan Hydrogels Promote Chondrogenic Stem Cell Differentiation

et al. 2017

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Gelatin–hyaluronic acid (Gel–HA) hybrid hydrogels have been proposed as matrices for tissue engineering because of their ability to mimic the architecture of the extracellular matrix. Our aim was to explore whether tyramine conjugates of Gel and HA, producing injectable hydrogels, are able to induce a particular phenotype of encapsulated human mesenchymal stem cells without the need for growth factors. While pure Gel allowed good cell adhesion without remarkable differentiation and pure HA triggered chondrogenic differentiation without cell spreading, the hybrids, especially those rich in HA, promoted chondrogenic differentiation as well as cell proliferation and adhesion. Secretion of chondrogenic markers such as aggrecan, SOX-9, collagen type II, and glycosaminoglycans was observed, whereas osteogenic, myogenic, and adipogenic markers (RUNX2, sarcomeric myosin, and lipoproteinlipase, respectively) were not present after 2 weeks in the growth medium. The most promising matrix for chondrogenesis seems to be a mixture containing 70% HA and 30% Gel as it is the material with the best mechanical properties from all compositions tested here, and at the same time, it provides an environment suitable for balanced cell adhesion and chondrogenic differentiation. Thus, it represents a system that has a high potential to be used as the injectable material for cartilage regeneration therapies.

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“…Yin's group generated the poly (l-glutamic acid) (PLGA) hydrogel porous scaffolds by lyophilization, which were then used to form adipose-derived stem cell (ASC) spheroids in the voids of the scaffolds (Figure 2b). [66] They found that the size of the spheroid was positively correlated with cell density. Furthermore, the enhancement of paracrine secretion attributing to the formation of the spheroid could upregulate angiogenic genes expression.…”

Section: Scaffold-based Culture Systemmentioning

confidence: 99%

Development of Cell Spheroids by Advanced Technologies

Shao

Chi

Zhang

et al. 2020

Adv Materials Technologies

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3D cell culture has been strongly advocated as a highly useful culture technique instead of the traditional 2D cell culture. Specially, spheroids, as the primary mode of 3D cell culture, allow cells to establish a connection between the cell and the extracellular matrix to form a specific 3D structure that better mimics the growing environment of cells in vivo. Benefiting from the emergence of various advanced micromachining platforms, spheroids have received increasing attention in diverse fields. Herein, the combination of the cell spheroid culture with microfluidic technology is reviewed. After concisely introducing the traditional methods for fabricating cell spheroids, an outline of the approaches for preparing cell spheroids using different advanced techniques is given. Then, the various applications of the generated cell spheroids in the field of biomedical engineering are presented and the current limitations, challenges, and future directions are summarized.

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Strategy for constructing vascularized adipose units in poly(l-glutamic acid) hydrogel porous scaffold through inducing in-situ formation of ASCs spheroids

Cited by 72 publications

References 37 publications

Scaffold-free generation of uniform adipose spheroids for metabolism research and drug discovery

Scaffold-free generation of uniform adipose spheroids for metabolism research and drug discovery

Hybrid Protein–Glycosaminoglycan Hydrogels Promote Chondrogenic Stem Cell Differentiation

Development of Cell Spheroids by Advanced Technologies

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