PMID- 35867788
OWN - NLM
STAT- MEDLINE
DCOM- 20220726
LR  - 20240923
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 8
IP  - 29
DP  - 2022 Jul 22
TI  - Engineered immunomodulatory accessory cells improve experimental allogeneic islet 
      transplantation without immunosuppression.
PG  - eabn0071
LID - 10.1126/sciadv.abn0071 [doi]
LID - eabn0071
AB  - 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.
FAU - Wang, Xi
AU  - Wang X
AUID- ORCID: 0000-0003-3415-7092
AD  - Department of Biological and Environmental Engineering, Cornell University, 
      Ithaca, NY 14853, USA.
FAU - Wang, Kai
AU  - Wang K
AUID- ORCID: 0000-0001-6240-0147
AD  - Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
AD  - Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
FAU - Yu, Ming
AU  - Yu M
AD  - Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, 
      PA 19104, USA.
FAU - Velluto, Diana
AU  - Velluto D
AD  - Diabetes Research Institute, University of Miami Miller School of Medicine, 
      Miami, FL 33136, USA.
FAU - Hong, Xuechong
AU  - Hong X
AUID- ORCID: 0000-0002-0804-672X
AD  - Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
AD  - Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
FAU - Wang, Bo
AU  - Wang B
AD  - Department of Biological and Environmental Engineering, Cornell University, 
      Ithaca, NY 14853, USA.
FAU - Chiu, Alan
AU  - Chiu A
AD  - Department of Biological and Environmental Engineering, Cornell University, 
      Ithaca, NY 14853, USA.
FAU - Melero-Martin, Juan M
AU  - Melero-Martin JM
AUID- ORCID: 0000-0002-4689-8149
AD  - Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
AD  - Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
AD  - Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
FAU - Tomei, Alice A
AU  - Tomei AA
AUID- ORCID: 0000-0002-5059-6303
AD  - Diabetes Research Institute, University of Miami Miller School of Medicine, 
      Miami, FL 33136, USA.
AD  - Department of Biomedical Engineering, University of Miami, Miami, FL 33146, USA.
AD  - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 
      33136, USA.
FAU - Ma, Minglin
AU  - Ma M
AUID- ORCID: 0000-0002-9553-7526
AD  - Department of Biological and Environmental Engineering, Cornell University, 
      Ithaca, NY 14853, USA.
LA  - eng
GR  - R01 DK105967/DK/NIDDK NIH HHS/United States
GR  - S10 OD025049/OD/NIH HHS/United States
PT  - Journal Article
DEP - 20220722
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Experimental/therapy
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Immunomodulation
MH  - Immunosuppression Therapy
MH  - *Islets of Langerhans Transplantation/methods
MH  - Mice
MH  - Mice, Inbred BALB C
PMC - PMC9307254
EDAT- 2022/07/23 06:00
MHDA- 2022/07/27 06:00
PMCR- 2022/07/22
CRDT- 2022/07/22 14:04
PHST- 2022/07/22 14:04 [entrez]
PHST- 2022/07/23 06:00 [pubmed]
PHST- 2022/07/27 06:00 [medline]
PHST- 2022/07/22 00:00 [pmc-release]
AID - abn0071 [pii]
AID - 10.1126/sciadv.abn0071 [doi]
PST - ppublish
SO  - Sci Adv. 2022 Jul 22;8(29):eabn0071. doi: 10.1126/sciadv.abn0071. Epub 2022 Jul 
      22.