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Cited by 62Pancreatic function and diabetesDiabetes and associated disordersMesenchymal stem cell research

Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression

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Wang, Xi, Wang, Kai, Yu, Ming, Velluto, Diana, Hong, Xuechong, Wang, Bo, Chiu, Alan, Melero-Martin, Juan M. +2 more·2022·Science Advances
DOI 10.1126/sciadv.abn0071PMC PMC9307254
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Abstract

Islet transplantation has been established as a viable treatment modality for type 1 diabetes. However, the side effects of the systemic immunosuppression required for patients often outweigh its benefits. Here, we engineer programmed death ligand-1 and cytotoxic T lymphocyte antigen 4 immunoglobulin fusion protein–modified mesenchymal stromal cells (MSCs) as accessory cells for islet cotransplantation. The engineered MSCs (eMSCs) improved the outcome of both syngeneic and allogeneic islet transplantation in diabetic mice and resulted in allograft survival for up to 100 days without any systemic immunosuppression. Immunophenotyping revealed reduced infiltration of CD4 + or CD8 + T effector cells and increased infiltration of T regulatory cells within the allografts cotransplanted with eMSCs compared to controls. The results suggest that the eMSCs can induce local immunomodulation and may be applicable in clinical islet transplantation to reduce or minimize the need of systemic immunosuppression and ameliorate its negative impact.

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  • These accessory mesenchymal stromal cells reduced infiltration of CD4+ and CD8+ effector T-cells and increased the number of Tregs to induce local immune tolerance.

    “These accessory mesenchymal stromal cells reduced infiltration of CD4+ and CD8+ effector T-cells and increased the number of Tregs to induce local immune tolerance.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [116]

  • Mesenchymal stromal cells engineered to overexpress PD-L1 and the CTLA4-Ig fusion protein, co-transplanted with allogenic mouse islets, reversed diabetes significantly longer than without the genetic modifications.

    “These gene-edited cells were co-transplanted with allogenic mouse islets to reverse diabetes significantly longer than without the genetic modifications.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [116]

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Authors
Wang, X., Wang, K., Yu, M., Velluto, D., Hong, X., Wang, B., Chiu, A., Melero-Martin, J. M., Tomei, A. A., & Ma, M.
Affiliations
  • Cornell University (US)
  • Boston Children's Hospital (US)
  • Hospital of the University of Pennsylvania (US)
  • University of Miami (US)
  • Department of Cardiac Surgery, Boston Children’s Hospital, Boston, MA 02115, USA.
Corresponding author
Ma, Minglin
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-07-22
Volume
8
Issue
29
Pages
eabn0071-eabn0071
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.abn0071
PMC
PMC9307254
OpenAlex
W4286586446
Cited by
62
References
79
Citations by year
2026: 13 · 2025: 16 · 2024: 15 · 2023: 13 · 2022: 5
FWCI
11.71
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk105967-05, 1s10od025049-01)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK105967)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
islet transplantation, type 1 diabetes, allogeneic islet transplantation, mesenchymal stem cells, immunomodulation, PD-L1, CTLA-4, regulatory T cells, allograft survival, immunosuppression reduction, T cell infiltration
MeSH terms
Animals, Diabetes Mellitus, Experimental, Immunosuppression Therapy, Mice, Inbred BALB C, Islets of Langerhans Transplantation, Hematopoietic Stem Cell Transplantation, Mice, Immunomodulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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