PMID- 34927459
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220310
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 322
IP  - 2
DP  - 2022 Feb 1
TI  - Considerations and challenges of islet transplantation and future therapies on 
      the horizon.
PG  - E109-E117
LID - 10.1152/ajpendo.00310.2021 [doi]
AB  - Islet transplantation is a treatment for selected adults with type 1 diabetes and 
      severe hypoglycemia. Islets from two or more donor pancreases, a scarce resource, 
      are usually required to impact glycemic control, but the treatment falls short of 
      a cure. Islets are avascular when transplanted into the hypoxic liver environment 
      and subjected to inflammatory insults, immune attack, and toxicity from systemic 
      immunosuppression. The Collaborative Islet Transplant Registry, with outcome data 
      on over 1,000 islet transplant recipients, has demonstrated that larger islet 
      numbers transplanted and older age of recipients are associated with better 
      outcomes. Induction with T-cell depleting agents and the TNF-alpha inhibitor 
      etanercept and maintenance systemic immunosuppression with mTOR inhibitors in 
      combination with calcineurin inhibitors also appear advantageous, but concerns 
      remain over immunosuppressive toxicity. We discuss strategies and therapeutics 
      that address specific challenges of islet transplantation, many of which are at 
      the preclinical stage of development. On the horizon are adjuvant cell therapies 
      with mesenchymal stromal cells and regulatory T cells that have been used in 
      preclinical models and in humans in other contexts; such a strategy may enable 
      reductions in immunosuppression in the early peri-transplant period when the 
      islets are vulnerable to apoptosis. Human embryonic stem cell-derived islets are 
      in early-phase clinical trials and hold the promise of an inexhaustible supply of 
      insulin-producing cells; effective encapsulation of such cells or, silencing of 
      the human leukocyte antigen (HLA) complex would eliminate the need for 
      immunosuppression, enabling this therapy to be used in all those with type 1 
      diabetes.
FAU - Walker, Sophie
AU  - Walker S
AD  - BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, 
      University of Edinburgh, Edinburgh, United Kingdom.
FAU - Appari, Mahesh
AU  - Appari M
AD  - BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, 
      University of Edinburgh, Edinburgh, United Kingdom.
FAU - Forbes, Shareen
AU  - Forbes S
AUID- ORCID: 0000-0002-9127-0641
AD  - BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, 
      University of Edinburgh, Edinburgh, United Kingdom.
AD  - Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
AD  - Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada.
LA  - eng
GR  - MR/S03692X/1/MRC_/Medical Research Council/United Kingdom
GR  - TCS/17/31/CSO_/Chief Scientist Office/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20211220
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (MTOR Inhibitors)
SB  - IM
MH  - Adult
MH  - Diabetes Mellitus, Type 1/*therapy
MH  - Humans
MH  - Hypoglycemia/*therapy
MH  - Immunosuppression Therapy/adverse effects
MH  - Islets of Langerhans/*blood supply/drug effects/*immunology
MH  - Islets of Langerhans Transplantation/*methods
MH  - MTOR Inhibitors/adverse effects
MH  - Middle Aged
MH  - *Registries
MH  - Transplantation, Homologous/methods
MH  - Treatment Outcome
OTO - NOTNLM
OT  - diabetes
OT  - immunosuppression
OT  - inflammation
OT  - islet transplantation
EDAT- 2021/12/21 06:00
MHDA- 2022/03/01 06:00
CRDT- 2021/12/20 08:42
PHST- 2021/12/21 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2021/12/20 08:42 [entrez]
AID - 10.1152/ajpendo.00310.2021 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2022 Feb 1;322(2):E109-E117. doi: 
      10.1152/ajpendo.00310.2021. Epub 2021 Dec 20.