Adipose-derived mesenchymal stem cell spheroid sheet accelerates regeneration of ulcerated oral mucosa by enhancing inherent therapeutic properties

Lee, Jennifer Sang jee; Kim, Se-Jeong; Choi, Ji Suk; Eom, Min Rye; Shin, Heungsoo; Kwon, Seong Keun

doi:10.1016/j.jiec.2020.08.013

Cited by 11 publications

(4 citation statements)

References 52 publications

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“…Likewise, size-controllable MSC spheroids had been fabricated from microscaled cell sheets for regenerative applications [ 32 ]. Conversely, ASC spheroids were seeded on a temperature-responsive hydrogel to fabricate cell sheets in another study [ 33 ]. In comparison with the transition between cell spheroids and cell sheets, the combination of the two forms of 3D culture can yield substantial advantages, including shortened culture time, more robust 3D matrix formation and easy cell transplantation.…”

Section: Discussionmentioning

confidence: 99%

Enhanced angiogenic potential of adipose-derived stem cell sheets by integration with cell spheroids of the same source

Hsu

Lee

et al. 2022

Stem Cell Res Ther

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Background Adipose-derived stem cell (ASC) has been considered as a desirable source for cell therapy. In contrast to combining scaffold materials with cells, ASCs can be fabricated into scaffold-free three-dimensional (3D) constructs to promote regeneration at tissue level. However, previous reports have found decreased expression of vascular endothelial growth factor (VEGF) in ASC sheets. In this study, we aimed to integrate ASC spheroids into ASC sheets to enhance the angiogenic capability of cell sheets. Methods ASCs were seeded in agarose microwells to generate uniform cell spheroids with adjustable size, while extracellular matrix deposition could be stimulated by ascorbic acid 2-phosphate to form ASC sheets. RNA sequencing was performed to identify the transcriptomic profiles of ASC spheroids and sheets relative to monolayer ASCs. By transferring ASC spheroids onto ASC sheets, the spheroid sheet composites could be successfully fabricated after a short-term co-culture, and their angiogenic potential was evaluated in vitro and in ovo. Results RNA sequencing analysis revealed that upregulation of angiogenesis-related genes was found only in ASC spheroids. The stimulating effect of spheroid formation on ASCs toward endothelial lineage was demonstrated by enhanced CD31 expression, which maintained after ASC spheroids were seeded on cell sheets. Relative to ASC sheets, enhanced expression of VEGF and hepatocyte growth factor was also noted in ASC spheroid sheets, and conditioned medium of ASC spheroid sheets significantly enhanced tube formation of endothelial cells in vitro. Moreover, chick embryo chorioallantoic membrane assay showed a significantly higher capillary density with more branch points after applying ASC spheroid sheets, and immunohistochemistry also revealed a significantly higher ratio of CD31-positive area. Conclusion In the spheroid sheet construct, ASC spheroids can augment the pro-angiogenesis capability of ASC sheets without the use of exogenous biomaterial or genetic manipulation. The strategy of this composite system holds promise as an advance in 3D culture technique of ASCs for future application in angiogenesis and regeneration therapies.

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Section: Discussionmentioning

confidence: 99%

Enhanced angiogenic potential of adipose-derived stem cell sheets by integration with cell spheroids of the same source

Hsu

Lee

et al. 2022

Stem Cell Res Ther

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“…Moreover, adipose-derived stem cell (ADSC) tablets can also promote peripheral nerve regeneration [134] and repair ulcerative oral mucosa [135]. In order to harvest cells from a culture medium with intact extracellular matrix (ECM) and preserved intercellular connections, many new materials and methods have been developed, among which nanomaterials are a hot topic.…”

Section: The Effect Of Stem Cell Sheetsmentioning

confidence: 99%

The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration

Wu,

Sun,

et al. 2024

Biomedicines

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Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.

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“…Oral ulcers caused by cancer therapies are becoming an increasing concern and may even trigger treatment discontinuation. Ulcer treatment using a 3D ASC spheroid sheet has been investigated 100 . An in vivo study using white rabbits showed that such a sheet formed a 3D multilayered epithelium that exhibited immunofluorescent staining for CK5 and CK13 (markers of basal and suprabasal cells, respectively), affording better epithelialization and faster wound closure compared to a 2D culture.…”

Section: Spheroid Applications In Tementioning

confidence: 99%

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

et al. 2021

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A spheroid is a complex, spherical cellular aggregate supporting cell-cell and cell-matrix interactions in an environment that mimics the real-world situation. In terms of tissue engineering, spheroids are important building blocks that replace two-dimensional cell cultures. Spheroids replicate tissue physiological activities. The use of spheroids with/without scaffolds yields structures that engage in desired activities and replicate the complicated geometry of three-dimensional tissues. In this mini-review, we describe conventional and novel methods by which scaffold-free and scaffolded spheroids may be fabricated and discuss their applications in tissue regeneration and future perspectives.

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Adipose-derived mesenchymal stem cell spheroid sheet accelerates regeneration of ulcerated oral mucosa by enhancing inherent therapeutic properties

Cited by 11 publications

References 52 publications

Enhanced angiogenic potential of adipose-derived stem cell sheets by integration with cell spheroids of the same source

Enhanced angiogenic potential of adipose-derived stem cell sheets by integration with cell spheroids of the same source

The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration

The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

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