PMID- 37029499
OWN - NLM
STAT- MEDLINE
DCOM- 20230608
LR  - 20240313
IS  - 1399-3089 (Electronic)
IS  - 0908-665X (Linking)
VI  - 30
IP  - 3
DP  - 2023 May-Jun
TI  - The case for the therapeutic use of mechanistic/mammalian target of rapamycin 
      (mTOR) inhibitors in xenotransplantation.
PG  - e12802
LID - 10.1111/xen.12802 [doi]
AB  - The mechanistic/mammalian target of rapamycin (mTOR) is one of the systems that 
      are necessary to maintain cell homeostasis, such as survival, proliferation, and 
      differentiation. mTOR inhibitors (mTOR-Is) are utilized as immunosuppressants and 
      anti-cancer drugs. In organ allotransplantation, current regimens infrequently 
      include an mTOR-I, which are positioned more commonly as alternative 
      immunosuppressants. In clinical allotransplantation, long-term efficacy has been 
      established, but there is a significant incidence of adverse events, for example, 
      inhibition of wound healing, buccal ulceration, anemia, hyperglycemia, 
      dyslipidemia, and thrombocytopenia, some of which are dose-dependent. mTOR-Is 
      have properties that may be especially beneficial in xenotransplantation. These 
      include suppression of T cell proliferation, increases in the number of T 
      regulatory cells, inhibition of pig graft growth, and anti-inflammatory, 
      anti-viral, and anti-cancer effects. We here review the potential benefits and 
      risks of mTOR-Is in xenotransplantation and suggest that the benefits exceed the 
      adverse effects.
CI  - (c) 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Maenaka, Akihiro
AU  - Maenaka A
AUID- ORCID: 0000-0002-6216-4890
AD  - Center for Transplantation Sciences, Department of Surgery, Massachusetts General 
      Hospital/Harvard Medical School, Boston, Massachusetts, USA.
FAU - Kinoshita, Kohei
AU  - Kinoshita K
AUID- ORCID: 0009-0004-3267-906X
AD  - Center for Transplantation Sciences, Department of Surgery, Massachusetts General 
      Hospital/Harvard Medical School, Boston, Massachusetts, USA.
FAU - Hara, Hidetaka
AU  - Hara H
AUID- ORCID: 0000-0002-4179-7365
AD  - College of Veterinary Medicine, Yunnan Agricultural University, Kunming, Yunnan, 
      China.
FAU - Cooper, David K C
AU  - Cooper DKC
AUID- ORCID: 0000-0002-8899-9431
AD  - Center for Transplantation Sciences, Department of Surgery, Massachusetts General 
      Hospital/Harvard Medical School, Boston, Massachusetts, USA.
LA  - eng
GR  - U19 AI090959/AI/NIAID NIH HHS/United States
GR  - AI090959/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20230407
PL  - Denmark
TA  - Xenotransplantation
JT  - Xenotransplantation
JID - 9438793
RN  - W36ZG6FT64 (Sirolimus)
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Swine
MH  - *Sirolimus/pharmacology/therapeutic use
MH  - Transplantation, Heterologous
MH  - *Immunosuppressive Agents/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - T-Lymphocytes, Regulatory
MH  - Mammals
OTO - NOTNLM
OT  - Tregs
OT  - graft growth
OT  - immunosuppression
OT  - inflammation
OT  - mTOR inhibitor
OT  - neoplasia
OT  - viral infection
OT  - xenotransplantation
EDAT- 2023/04/09 06:00
MHDA- 2023/06/08 06:42
CRDT- 2023/04/08 01:52
PHST- 2023/02/13 00:00 [received]
PHST- 2023/03/23 00:00 [accepted]
PHST- 2023/06/08 06:42 [medline]
PHST- 2023/04/09 06:00 [pubmed]
PHST- 2023/04/08 01:52 [entrez]
AID - 10.1111/xen.12802 [doi]
PST - ppublish
SO  - Xenotransplantation. 2023 May-Jun;30(3):e12802. doi: 10.1111/xen.12802. Epub 2023 
      Apr 7.