PMID- 33008073
OWN - NLM
STAT- MEDLINE
DCOM- 20210804
LR  - 20240330
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 10
DP  - 2020 Sep 30
TI  - Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human 
      Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis.
LID - 10.3390/cells9102218 [doi]
LID - 2218
AB  - Human adipose-derived stem cells (ASCs) show immense promise for treating 
      inflammatory diseases, attributed primarily to their potent paracrine signaling. 
      Previous investigations demonstrated that short-term Rapamycin preconditioning of 
      bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a 
      pleiotropic molecule with therapeutic effects in the experimental autoimmune 
      encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced 
      immunosuppressive capacity in vitro. However, this has yet to be examined in 
      ASCs. The present study examined the therapeutic potential of short-term 
      Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak 
      disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), 
      or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease 
      scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. 
      These results correlated with augmented CD4(+) T helper (T(h)) and T regulatory 
      (T(reg)) cell populations in the spinal cord, and increased gene expression of 
      interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC 
      mice showed no improvement in clinical disease scores, reduced myelin levels, and 
      significantly less T(h) and T(reg) cells in the spinal cord. These findings 
      suggest that short-term Rapamycin preconditioning reduces the therapeutic 
      efficacy of ASCs when applied to late-stage EAE.
FAU - Wise, Rachel M
AU  - Wise RM
AD  - Neuroscience Program, Tulane Brain Institute, Tulane University School of Science 
      & Engineering, New Orleans, LA 70118, USA.
AD  - Center for Stem Cell Research & Regenerative Medicine, Tulane University School 
      of Medicine, New Orleans, LA 70112, USA.
FAU - Harrison, Mark A A
AU  - Harrison MAA
AUID- ORCID: 0000-0003-4685-3757
AD  - Neuroscience Program, Tulane Brain Institute, Tulane University School of Science 
      & Engineering, New Orleans, LA 70118, USA.
AD  - Center for Stem Cell Research & Regenerative Medicine, Tulane University School 
      of Medicine, New Orleans, LA 70112, USA.
FAU - Sullivan, Brianne N
AU  - Sullivan BN
AD  - Neuroscience Program, Tulane Brain Institute, Tulane University School of Science 
      & Engineering, New Orleans, LA 70118, USA.
AD  - Center for Stem Cell Research & Regenerative Medicine, Tulane University School 
      of Medicine, New Orleans, LA 70112, USA.
FAU - Al-Ghadban, Sara
AU  - Al-Ghadban S
AUID- ORCID: 0000-0001-8544-5751
AD  - Center for Stem Cell Research & Regenerative Medicine, Tulane University School 
      of Medicine, New Orleans, LA 70112, USA.
AD  - Department of Microbiology, Immunology and Genetics, University of North Texas 
      Health Science Center, Fort Worth, TX 76107, USA.
FAU - Aleman, Sarah J
AU  - Aleman SJ
AD  - Neuroscience Program, Tulane Brain Institute, Tulane University School of Science 
      & Engineering, New Orleans, LA 70118, USA.
FAU - Vinluan, Amber T
AU  - Vinluan AT
AD  - Neuroscience Program, Tulane Brain Institute, Tulane University School of Science 
      & Engineering, New Orleans, LA 70118, USA.
FAU - Monaco, Emily R
AU  - Monaco ER
AD  - Neuroscience Program, Tulane Brain Institute, Tulane University School of Science 
      & Engineering, New Orleans, LA 70118, USA.
FAU - Donato, Umberto M
AU  - Donato UM
AD  - Neuroscience Program, Tulane Brain Institute, Tulane University School of Science 
      & Engineering, New Orleans, LA 70118, USA.
FAU - Pursell, India A
AU  - Pursell IA
AUID- ORCID: 0000-0002-7207-3589
AD  - Center for Stem Cell Research & Regenerative Medicine, Tulane University School 
      of Medicine, New Orleans, LA 70112, USA.
FAU - Bunnell, Bruce A
AU  - Bunnell BA
AD  - Center for Stem Cell Research & Regenerative Medicine, Tulane University School 
      of Medicine, New Orleans, LA 70112, USA.
AD  - Department of Microbiology, Immunology and Genetics, University of North Texas 
      Health Science Center, Fort Worth, TX 76107, USA.
AD  - Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 
      70112, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200930
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Anti-Bacterial Agents)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology/*therapeutic use
MH  - Disease Models, Animal
MH  - Humans
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Multiple Sclerosis/*drug therapy
MH  - Sirolimus/*adverse effects/pharmacology
PMC - PMC7600854
OTO - NOTNLM
OT  - Rapamycin
OT  - adipose tissue-derived stem cells (ASCs)
OT  - demyelination
OT  - experimental autoimmune encephalomyelitis (EAE)
OT  - immunomodulation
OT  - inflammation
OT  - multiple sclerosis (MS)
COIS- The authors declare no conflict of interest.
EDAT- 2020/10/04 06:00
MHDA- 2021/08/05 06:00
PMCR- 2020/10/01
CRDT- 2020/10/03 01:01
PHST- 2020/08/24 00:00 [received]
PHST- 2020/09/16 00:00 [revised]
PHST- 2020/09/28 00:00 [accepted]
PHST- 2020/10/03 01:01 [entrez]
PHST- 2020/10/04 06:00 [pubmed]
PHST- 2021/08/05 06:00 [medline]
PHST- 2020/10/01 00:00 [pmc-release]
AID - cells9102218 [pii]
AID - cells-09-02218 [pii]
AID - 10.3390/cells9102218 [doi]
PST - epublish
SO  - Cells. 2020 Sep 30;9(10):2218. doi: 10.3390/cells9102218.