PMID- 30876741
OWN - NLM
STAT- MEDLINE
DCOM- 20200318
LR  - 20200401
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Print)
IS  - 1465-3249 (Linking)
VI  - 21
IP  - 4
DP  - 2019 Apr
TI  - Pleiotropic roles of autophagy in stem cell-based therapies.
PG  - 380-392
LID - S1465-3249(19)30028-3 [pii]
LID - 10.1016/j.jcyt.2019.02.007 [doi]
AB  - Stem cells (SCs) have been proven to possess regenerative and immunomodulatory 
      properties and can be used to treat diseases that involve loss of cells due to 
      tissue damage or inflammation. For this approach to succeed, SCs or their 
      derivatives should be able to engraft in the target tissue at least for a short 
      period of time. Unfortunately, once injected, therapeutic SCs will encounter a 
      hostile environment, including hypoxia, lack of nutrients and stromal support, 
      and cells may also be targeted and rejected by the immune system. Therefore, SC's 
      stress-response mechanisms likely play a significant role in survival of injected 
      cells and possibly contribute to their therapeutic efficacy. Autphagy, a 
      stress-response pathway, is involved in many different cellular processes, such 
      as survival during hypoxia and nutrient deprivation, cellular differentiation and 
      de-differentiation, and it can also contribute to their immunovisibility by 
      regulating antigen presentation and cytokine secretion. Autophagy machinery 
      interacts with many proteins and signaling pathways that regulate SC properties, 
      including PI3K/Akt, mammalian target of rapamycin (mTOR), Wnt, Hedgehog and 
      Notch, and it is also involved in regulating intracellular reactive oxygen 
      species (ROS) levels. In this review, we contend that autophagy is an important 
      therapeutic target that can be used to improve the outcome of SC-based tissue 
      repair and regeneration. Further research should reveal whether inhibition or 
      stimulation of autophagy increases the therapeutic utility of SCs and it should 
      also identify appropriate therapeutic regimens that can be applied in the clinic.
CI  - Copyright (c) 2019 International Society for Cell and Gene Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Beljanski, Vladimir
AU  - Beljanski V
AD  - NSU Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, 
      Florida, USA. Electronic address: vbeljanski@nova.edu.
FAU - Grinnemo, Karl-Henrik
AU  - Grinnemo KH
AD  - Department of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery 
      and Anesthesiology, Karolinska Institutet, Karolinska University Hospital, 
      Stockholm, Sweden; Department of Surgical Sciences, Division of Cardiothoracic 
      Surgery and Anesthesiology, Uppsala University, Akademiska University Hospital, 
      Uppsala, Sweden.
FAU - Osterholm, Cecilia
AU  - Osterholm C
AD  - Department of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery 
      and Anesthesiology, Karolinska Institutet, Karolinska University Hospital, 
      Stockholm, Sweden.
LA  - eng
GR  - R15 GM128189/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190312
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Cell Differentiation
MH  - Extracellular Matrix/metabolism
MH  - Humans
MH  - Signal Transduction
MH  - *Stem Cell Transplantation
MH  - Stem Cells/*cytology
PMC - PMC6538418
MID - NIHMS1523845
EDAT- 2019/03/17 06:00
MHDA- 2020/03/19 06:00
PMCR- 2020/04/01
CRDT- 2019/03/17 06:00
PHST- 2018/10/19 00:00 [received]
PHST- 2019/01/25 00:00 [revised]
PHST- 2019/02/19 00:00 [accepted]
PHST- 2019/03/17 06:00 [pubmed]
PHST- 2020/03/19 06:00 [medline]
PHST- 2019/03/17 06:00 [entrez]
PHST- 2020/04/01 00:00 [pmc-release]
AID - S1465-3249(19)30028-3 [pii]
AID - 10.1016/j.jcyt.2019.02.007 [doi]
PST - ppublish
SO  - Cytotherapy. 2019 Apr;21(4):380-392. doi: 10.1016/j.jcyt.2019.02.007. Epub 2019 
      Mar 12.