Millimeter-thick xenoislet-laden fibers as retrievable transplants mitigate foreign body reactions for long-term glycemic control in diabetic mice

Watanabe, Takeru; Okitsu, Teru; Ozawa, Fumisato; Nagata, Shogo; Matsunari, Hitomi; Nagashima, Hiroshi; Nagaya, Masaki; Teramae, Hiroyuki; Takeuchi, Shoji

doi:10.1016/j.biomaterials.2020.120162

Cited by 23 publications

(20 citation statements)

References 43 publications

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“…Recently, it was reported that hydrogel capsules larger than 1-mm-thick tend to mitigate FBR (Watanabe et al, 2020, Veiseh et al, 2015. In our experiment, however, when 1-mm-thick grafts encapsulating hSC-bs ll OPEN…”

Section: Discussionmentioning

confidence: 49%

“…To produce 1 mm-thick grafts encapsulating hSC-βs, the microfluidic device was 134 fabricated by using glass capillaries and connectors (T. Watanabe et al 2020). The device 135 and all tubing sections were sterilized by washing them with 70% ethanol for 10 min.…”

Section: Fabrication Of 1 Mm-thick Graft Encapsulating Hsc-β 133mentioning

confidence: 99%

“…Figure 1 shows the structure of the proposed LENCON with millimeter-thickness. Grafts with millimeter-thickness tend to mitigate FBR (Watanabe et al, 2020, Veiseh et al, 2015, as well as exhibit higher mechanical strength. The cells are placed near the edge of the lotus-root-shaped graft structure to support cell survival.…”

Section: Introductionmentioning

confidence: 99%

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Lotus-root-shaped cell-encapsulated construct as a retrieval graft for long-term transplantation of human iPSC-derived β-cells

et al. 2021

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Cell therapy using human-stem-cell-derived pancreatic beta cells (hSC-bs) is a potential treatment method for type 1 diabetes mellitus (T1D). For therapeutic safety, hSC-bs need encapsulation in grafts that are scalable and retrievable. In this study, we developed a lotus-root-shaped cell-encapsulated construct (LENCON) as a graft that can be retrieved after long-term hSC-b transplantation. This graft had six multicores encapsulating hSC-bs located within 1 mm from the edge. It controlled the recipient blood glucose levels for a long-term, following transplantation in immunodeficient diabetic mice. LENCON xenotransplanted into immunocompetent mice exhibited retrievability and maintained the functionality of hSC-bs for over 1 year after transplantation. We believe that LENCON can contribute to the treatment of T1D through long-term transplantation of hSC-bs and in many other forms of cell therapy.

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Section: Discussionmentioning

confidence: 49%

Section: Fabrication Of 1 Mm-thick Graft Encapsulating Hsc-β 133mentioning

confidence: 99%

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Lotus-root-shaped cell-encapsulated construct as a retrieval graft for long-term transplantation of human iPSC-derived β-cells

et al. 2021

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“…reported that the xenoislet‐laden fiber‐shaped hydrogel could mitigate in vivo cellular deposition when the diameter of hydrogel is more than 1.0 mm, which was used for long‐term glycemic control in diabetic mice. [ 152 ] In addition to the size, scaffold orientation has been shown to affect the immune responses. Anderson et al.…”

Section: Conventional Strategies To Migrate the Fbrmentioning

confidence: 99%

Dealing with the Foreign‐Body Response to Implanted Biomaterials: Strategies and Applications of New Materials

Zhang

Chen

Shi

et al. 2020

Adv Funct Materials

161

139

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Foreign‐body response caused by implanted biomaterials seriously impedes the function of implants and is a major obstacle to the development of implantable biomaterials and medical devices. Recent advances in implantable biomaterials and medical devices have provided strategies to resist the foreign‐body response. In this review, the mechanism of the foreign‐body response and conventional strategies to mitigate foreign‐body response is briefly introduced. Then, three types of promising foreign‐body response resisting materials are focused and the advantages, characteristics, and applications of each material are discussed. Finally, prospects are put forward for future development of foreign‐body response resisting materials and current challenges that require in‐depth study.

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“…The FBR of implants will lead to cutting off of nutrient transportation, painful tissue deformation, and even implant failure. Divergent from the need of anti-FBR requirements in clinical practice, a very limited number of anti-FBR materials were reported, and developing low FBR materials is still a formidable challenge [13][14][15][16][17][18][19][20][21][22][23][24][25][26] . Moreover, the increasing clinical demand on implantable biomaterials and medical devices urgently calls for high-efficiency anti-FBR materials with easy and scalable synthesis, low cost, and high solubility in water to avoid using organic solvent during material processing for biomedical application.…”

mentioning

confidence: 99%

Bio-inspired poly-DL-serine materials resist the foreign-body response

Zhang

Chen

et al. 2021

Nat Commun

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Implantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants. The high L-serine content in low immunogenic silk sericin, and the high D-serine content as a neurotransmitter together inspire us to prepare poly-DL-serine (PSer) materials in mitigating the FBR. Here we report highly water soluble, biocompatible and easily accessible PSer hydrogels that cause negligible inflammatory response after subcutaneous implantation in mice for 1 week and 2 weeks. No obvious collagen capsulation is found surrounding the PSer hydrogels after 4 weeks, 3 months and 7 months post implantation. Histological analysis on inflammatory cytokines and RNA-seq assay both indicate that PSer hydrogels show low FBR, comparable to the Mock group. The anti-FBR performance of PSer hydrogels at all time points surpass the poly(ethyleneglycol) hydrogels that is widely utilized as bio-inert materials, implying the potent and wide application of PSer materials in implantable biomaterials and biomedical devices.

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Millimeter-thick xenoislet-laden fibers as retrievable transplants mitigate foreign body reactions for long-term glycemic control in diabetic mice

Cited by 23 publications

References 43 publications

Lotus-root-shaped cell-encapsulated construct as a retrieval graft for long-term transplantation of human iPSC-derived β-cells

Lotus-root-shaped cell-encapsulated construct as a retrieval graft for long-term transplantation of human iPSC-derived β-cells

Dealing with the Foreign‐Body Response to Implanted Biomaterials: Strategies and Applications of New Materials

Bio-inspired poly-DL-serine materials resist the foreign-body response

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