PMID- 31534540
OWN - NLM
STAT- MEDLINE
DCOM- 20200928
LR  - 20200928
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 9
IP  - 21
DP  - 2019
TI  - Noninvasive application of mesenchymal stem cell spheres derived from hESC 
      accelerates wound healing in a CXCL12-CXCR4 axis-dependent manner.
PG  - 6112-6128
LID - 10.7150/thno.32982 [doi]
AB  - Mesenchymal stem cells (MSC) derived from adult tissues effectively promote wound 
      healing. However, MSC quality varies, and the quantity of MSC is limited, as MSC 
      are acquired through donations. Moreover, the survival and functioning of 
      dissociated MSC delivered to an inflammatory lesion are subject to challenges. 
      Methods: Here, spheres (EMSC(Sp)) generated from human embryonic stem 
      cell-derived MSC (EMSC) were directly dropped onto excised wounds in mice; the 
      effects of EMSC(Sp) were compared to those of dissociated EMSC (EMSC(Diss)). 
      Following transplantation, we measured the extent of wound closure, dissected the 
      histological features of the wounds, determined transcriptomic changes in cells 
      isolated from the treated and control wounds, and evaluated the molecular 
      mechanism of the effects of EMSC. Results: The application of EMSC(Sp) onto 
      murine dermal wounds substantially increased survival and efficacy of EMSC 
      compared to the topical application of EMSC(Diss). RNA sequencing (RNA-Seq) of 
      cells isolated from the wounds highlighted the involvement of CXCL12-CXCR4 
      signaling in the effects of EMSC(Sp), which was verified in EMSC via CXCL12 
      knockdown and in target cells (vascular endothelial cells, epithelial 
      keratinocytes, and macrophages) via CXCR4 inhibition. Finally, we enhanced the 
      biosafety of EMSC(Sp) by engineering cells with an inducible suicide gene. 
      Conclusions: Together, these data suggest the topical application of EMSC(Sp) as 
      an unlimited, quality-assured, safe, and noninvasive therapy for wound healing 
      and the CXCL12-CXCR4 axis as a key player in this treatment.
FAU - Wang, Xiaoyan
AU  - Wang X
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
FAU - Jiang, Bin
AU  - Jiang B
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
FAU - Sun, Huiyan
AU  - Sun H
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
AD  - School of Artificial Intelligence, Jilin University, Changchun, China.
FAU - Zheng, Dejin
AU  - Zheng D
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
FAU - Zhang, Zhenwu
AU  - Zhang Z
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
FAU - Yan, Li
AU  - Yan L
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
FAU - Li, Enqin
AU  - Li E
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
FAU - Wu, Yaojiong
AU  - Wu Y
AD  - The Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at 
      Shenzhen, Tsinghua University, Shenzhen, China.
FAU - Xu, Ren-He
AU  - Xu RH
AD  - Center of Reproduction, Development & Aging, and Institute of Translational 
      Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190814
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (CXCR4 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Administration, Topical
MH  - Animals
MH  - Chemokine CXCL12/genetics/*metabolism
MH  - Endothelial Cells/physiology
MH  - Gene Knockdown Techniques
MH  - Human Embryonic Stem Cells/physiology
MH  - Humans
MH  - Keratinocytes/physiology
MH  - Macrophages/physiology
MH  - Mesenchymal Stem Cells/physiology
MH  - Mice
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - Signal Transduction
MH  - Skin/injuries/pathology
MH  - Spheroids, Cellular/physiology
MH  - *Wound Healing
PMC - PMC6735514
OTO - NOTNLM
OT  - CXCL12/CXCR4
OT  - Human embryonic stem cells
OT  - mesenchymal stem cells
OT  - spheroids
OT  - wound healing
COIS- Competing Interests: R.X. is a founder of ImStem Biotechnology, Inc., a stem cell 
      company. The other authors declare no competing financial interests.
EDAT- 2019/09/20 06:00
MHDA- 2020/09/29 06:00
PMCR- 2019/01/01
CRDT- 2019/09/20 06:00
PHST- 2019/01/09 00:00 [received]
PHST- 2019/06/29 00:00 [accepted]
PHST- 2019/09/20 06:00 [entrez]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/09/29 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - thnov09p6112 [pii]
AID - 10.7150/thno.32982 [doi]
PST - epublish
SO  - Theranostics. 2019 Aug 14;9(21):6112-6128. doi: 10.7150/thno.32982. eCollection 
      2019.