<i>In situ</i> transplantation of adipose tissue‐derived stem cells organized on porous polymer nanosheets for murine skin defects

Nishiwaki, K; Aoki, Shimpo; Kinoshita, Manabu; Kiyosawa, Tomoharu; Suematsu, Yoshitaka; Takeoka, Shinji; Fujie, Toshinori

doi:10.1002/jbm.b.34228

Cited by 17 publications

(14 citation statements)

References 32 publications

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“…The nanosheet has strong physical adsorption via Van der Waals forces due to its thinness 23 . Hence, a nanosheet can be an excellent scaffold that carries ASCs onto the wound without the need for an adhesive agent 24 . Nishiwaki et al reported the wound healing effect of ASC transplantation with a tri-layered porous nanosheet.…”

Section: Introductionmentioning

confidence: 99%

Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds

Nagano

Suematsu

Takuma

et al. 2021

Sci Rep

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The short survival time of transplanted adipose-derived mesenchymal stem cells (ASCs) is a problem for skin wound healing. Transplantation after the formation of cellular spheroids has been investigated as a promising method for prolonging cellular survival. However, there have been technical restrictions for transplantation of spheroids in clinical practice. Here, we show an effective method for transplantation of ASC spheroids onto skin wounds in order to efficiently cure refractory ulcers. To assist anchoring of spheroids onto skin wounds, we used a 120-nm-thick free-standing film (nanosheet) that has a highly adhesive property. Bioluminescence imaging showed that ASC spheroids carried by the nanosheet survived for 14 days, which is about two-times longer than that previously reported. Wounds treated with a nanosheet carrying ASC spheroids were 4-times smaller than untreated wounds on day 14. This method for transplantation of spheroids could be applied to cell therapy for various refractory skin wounds.

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Section: Introductionmentioning

confidence: 99%

Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds

Nagano

Suematsu

Takuma

et al. 2021

Sci Rep

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“…ECM proteins such as fibronectin, collagen and laminin penetrate through the micropores to stabilize cell hierarchies constructed between multi-layered porous nanosheets. Additionally, it has been reported that porous nanosheets facilitated long-term cell culture (up to 2 weeks) with more than 80% cell viability and oriented cell arrangement ( Nishiwaki et al, 2019 ). Most recently, we reported for the first time that porous nanosheets prepared by a solvent etching method could support the adipose-tissue derived stem cell (ASC) spheroids for high-magnification imaging owing to its transparency ( Suematsu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Ultra-Thin Porous PDLLA Films Promote Generation, Maintenance, and Viability of Stem Cell Spheroids

Tsai

Fernández

et al. 2021

Front. Bioeng. Biotechnol.

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Three-dimensional (3D) culture bridges and minimizes the gap between in vitro and in vivo states of cells and various 3D culture systems have been developed according to different approaches. However, most of these approaches are either complicated to operate, or costive to scale up. Therefore, a simple method for stem cell spheroid formation and preservation was proposed using poly(D,L-lactic acid) porous thin film (porous nanosheet), which were fabricated by a roll-to-roll gravure coating method combining a solvent etching process. The obtained porous nanosheet was less than 200 nm in thickness and had an average pore area of 6.6 μm2 with a porosity of 0.887. It offered a semi-adhesive surface for stem cells to form spheroids and maintained the average spheroid diameter below 100 μm for 5 days. In comparison to the spheroids formed in suspension culture, the porous nanosheets improved cell viability and cell division rate, suggesting the better feasibility to be applied as 3D culture scaffolds.

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“…We recently demonstrated the transplantation of ASCs using this multilayered porous nanosheet and showed promotion of the wound healing effects against skin defects 27 . However, considering the spatial limitation of the nanosheet for loading ASCs on its surface, this approach transplanting 2D adhesive cells is insufficient for secreting sufficient growth factors to induce angiogenesis for the treatment of skin ulcers.…”

Section: Introductionmentioning

confidence: 99%

Angiogenic efficacy of ASC spheroids filtrated on porous nanosheets for the treatment of a diabetic skin ulcer

et al. 2021

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Stem cell transplantation is expected to be an effective treatment for intractable skin ulcers by promoting angiogenesis; however, it is challenging to quickly realize a sufficient bloodstream for the ulcers. For this treatment, sheet‐like materials with monolayer cells such as cell sheets have been investigated. However, they have a limitation of cell number that can be transplanted at one time due to the two‐dimensional, monolayer cell structure, and sufficient secretion of growth factors cannot be expected. In this regard, cellular aggregates, such as spheroids, can reproduce three‐dimensional cell‐cell interactions that cause biological functions of living tissues more representative than monolayer cells, which is important to achieving efficient secretion of growth factors. In this study, we focused on free‐standing porous polymer ultrathin films (“porous nanosheets”) comprising poly(d,l‐lactic acid) (PDLLA) and succeeded in developing a spheroid‐covered nanosheet, on which more than 1000 spheroids from adipose‐tissue derived stem cells (ASCs) were loaded. The porous structure with an average pore diameter of 4 μm allowed for facile filtration and carrying spheroids on the nanosheet, as well as sufficient oxygen and nutrients inflow to the cells. The spheroid‐covered nanosheet achieved homogeneous transference of spheroids to a whole skin defect in diabetic model mice. Given the continuous release of vascular endothelial growth factor (VEGF) from the spheroids, the transplanted spheroids promoted healing with more accelerated angiogenesis than a nanosheet with a monolayer of cells. The spheroid‐covered nanosheet may be a new regenerative material for promoting intractable skin ulcer healing.

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In situ transplantation of adipose tissue‐derived stem cells organized on porous polymer nanosheets for murine skin defects

Abstract: This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 17 publications

References 32 publications

Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds

Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds

Ultra-Thin Porous PDLLA Films Promote Generation, Maintenance, and Viability of Stem Cell Spheroids

Angiogenic efficacy of ASC spheroids filtrated on porous nanosheets for the treatment of a diabetic skin ulcer

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