PMID- 35639473
OWN - NLM
STAT- MEDLINE
DCOM- 20220623
LR  - 20230808
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 7
IP  - 12
DP  - 2022 Jun 22
TI  - Bioactive extracellular vesicles from a subset of endothelial progenitor cells 
      rescue retinal ischemia and neurodegeneration.
LID - 10.1172/jci.insight.155928 [doi]
LID - e155928
AB  - Disruption of the neurovascular unit (NVU) underlies the pathophysiology of 
      various CNS diseases. One strategy to repair NVU dysfunction uses stem/progenitor 
      cells to provide trophic support to the NVU's functionally coupled and 
      interdependent vasculature and surrounding CNS parenchyma. A subset of 
      endothelial progenitor cells, endothelial colony-forming cells (ECFCs) with high 
      expression of the CD44 hyaluronan receptor (CD44hi), provides such 
      neurovasculotrophic support via a paracrine mechanism. Here, we report that 
      bioactive extracellular vesicles from CD44hi ECFCs (EVshi) are paracrine 
      mediators, recapitulating the effects of intact cell therapy in murine models of 
      ischemic/neurodegenerative retinopathy; vesicles from ECFCs with low expression 
      levels of CD44 (EVslo) were ineffective. Small RNA sequencing comparing the 
      microRNA cargo from EVshi and EVslo identified candidate microRNAs that 
      contribute to these effects. EVshi may be used to repair NVU dysfunction through 
      multiple mechanisms to stabilize hypoxic vasculature, promote vascular growth, 
      and support neural cells.
FAU - Marra, Kyle V
AU  - Marra KV
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, 
      California, USA.
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, 
      California, USA.
FAU - Aguilar, Edith
AU  - Aguilar E
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, 
      California, USA.
FAU - Guoqin, Wei
AU  - Guoqin W
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, 
      California, USA.
FAU - Usui-Ouchi, Ayumi
AU  - Usui-Ouchi A
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, 
      California, USA.
FAU - Ideguchi, Yochiro
AU  - Ideguchi Y
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, 
      California, USA.
FAU - Sakimoto, Susumu
AU  - Sakimoto S
AD  - Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, 
      Japan.
FAU - Friedlander, Martin
AU  - Friedlander M
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, 
      California, USA.
AD  - Lowy Medical Research Institute, La Jolla, California, USA.
LA  - eng
GR  - F30 EY029141/EY/NEI NIH HHS/United States
GR  - S10 OD023555/OD/NIH HHS/United States
GR  - T32 GM007198/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220622
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Animals
MH  - *Endothelial Progenitor Cells/metabolism
MH  - *Extracellular Vesicles/metabolism
MH  - Ischemia/metabolism
MH  - Mice
MH  - *MicroRNAs/genetics/metabolism
MH  - Neovascularization, Physiologic/physiology
MH  - *Retinal Diseases/metabolism/therapy
PMC - PMC9309054
OTO - NOTNLM
OT  - Adult stem cells
OT  - Neurodegeneration
OT  - Ophthalmology
OT  - Retinopathy
OT  - Vascular Biology
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2022/06/01 06:00
MHDA- 2022/06/24 06:00
PMCR- 2022/06/22
CRDT- 2022/05/31 15:58
PHST- 2021/10/18 00:00 [received]
PHST- 2022/05/13 00:00 [accepted]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/06/24 06:00 [medline]
PHST- 2022/05/31 15:58 [entrez]
PHST- 2022/06/22 00:00 [pmc-release]
AID - 155928 [pii]
AID - 10.1172/jci.insight.155928 [doi]
PST - epublish
SO  - JCI Insight. 2022 Jun 22;7(12):e155928. doi: 10.1172/jci.insight.155928.