PMID- 32389831
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20200625
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 255
DP  - 2020 Aug 15
TI  - Cotransplantation of human umbilical cord mesenchymal stem cells and endothelial 
      cells for angiogenesis and pulp regeneration in vivo.
PG  - 117763
LID - S0024-3205(20)30511-7 [pii]
LID - 10.1016/j.lfs.2020.117763 [doi]
AB  - AIMS: To explored the potential of human umbilical cord mesenchymal stem cells 
      (hUCMSCs) as seed cells for dental pulp regeneration and the possibility of 
      cotransplantation hUCMSCs and endothelial cells (ECs) for angiogenesis and pulp 
      regeneration in vivo. MATERIALS AND METHODS: hUCMSCs and human umbilical vein 
      endothelial cells (HUVECs) were cocultured for matrigel angiogenesis assay in 
      vitro and Matrigel plug assay in vivo. Next, we used the transwell coculture 
      system to coculture hUCMSCs and HUVECs in vitro for RNA- sequencing (RNA-seq). 
      Last, encapsulated hUCMSCs and HUVECs in scaffolds were injected into the root 
      segments, and transplanted into immunodeficient mice for dental pulp 
      regeneration. KEY FINDINGS: In vitro Matrigel angiogenesis assay and in vivo 
      Matrigel plug assay indicated that cocultured hUCMSCs and HUVECs promote vascular 
      formation of HUVECs, especially in 1:5 (hUCMSCs:HUVECs) coculture group. The 
      RNA-seq result indicated that cocultured HUVECs exhibited high Hif-1 signaling 
      pathway activity. We performed the cell transfection assay to knock down 
      HIF1A-AS2 in HUVECs and then coculture with hUCMSCs, and the expression of VEGFA, 
      HIF1A and PECAM1 were reduced. In pulp regeneration assay, Cotransplantation of 
      hUCMSCs and HUVECs (1,5) group showed pulp-like tissue regeneration. 
      SIGNIFICANCE: Cocultured hUCMSCs and HUVECs can promote vascular formation of 
      HUVECs, and the optimal coculture ration is 1:5 (hUCMSCs:HUVECs). hUCMSCs promote 
      angiogenesis of HUVECs through the long noncoding RNA HIF1A-AS2-activation of the 
      Hif-1 signaling pathway. Cotransplantation of hUCMSCs and HUVECs can regenerate 
      dental pulp-like tissue in vivo.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Zhang, Shuang
AU  - Zhang S
AD  - The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng 
      Street, Nangang District, Harbin 150001, China; Department of Endodontics, School 
      of Stomatology, Harbin Medical University, No. 143 Yiman Street, Nangang 
      District, Harbin 150001, China.
FAU - Zhang, Weiwei
AU  - Zhang W
AD  - The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng 
      Street, Nangang District, Harbin 150001, China; Department of Endodontics, School 
      of Stomatology, Harbin Medical University, No. 143 Yiman Street, Nangang 
      District, Harbin 150001, China.
FAU - Li, Yanping
AU  - Li Y
AD  - The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng 
      Street, Nangang District, Harbin 150001, China; Department of Endodontics, School 
      of Stomatology, Harbin Medical University, No. 143 Yiman Street, Nangang 
      District, Harbin 150001, China.
FAU - Ren, Liping
AU  - Ren L
AD  - Department of Prosthodontics, The First Affiliated Hospital of Harbin Medical 
      University, No. 143 Yiman Street, Nangang District, Harbin 150001, China.
FAU - Deng, Haotian
AU  - Deng H
AD  - The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng 
      Street, Nangang District, Harbin 150001, China; Department of Endodontics, School 
      of Stomatology, Harbin Medical University, No. 143 Yiman Street, Nangang 
      District, Harbin 150001, China.
FAU - Yin, Xiaowei
AU  - Yin X
AD  - The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng 
      Street, Nangang District, Harbin 150001, China; Department of Endodontics, School 
      of Stomatology, Harbin Medical University, No. 143 Yiman Street, Nangang 
      District, Harbin 150001, China.
FAU - Gao, Xu
AU  - Gao X
AD  - Department of Biochemistry and Molecular Biology, Harbin Medical University, 
      Harbin 150081, China.
FAU - Pan, Shuang
AU  - Pan S
AD  - The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng 
      Street, Nangang District, Harbin 150001, China; Department of Endodontics, School 
      of Stomatology, Harbin Medical University, No. 143 Yiman Street, Nangang 
      District, Harbin 150001, China. Electronic address: panshuang@hrbmu.edu.cn.
FAU - Niu, Yumei
AU  - Niu Y
AD  - The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng 
      Street, Nangang District, Harbin 150001, China; Department of Endodontics, School 
      of Stomatology, Harbin Medical University, No. 143 Yiman Street, Nangang 
      District, Harbin 150001, China. Electronic address: niuym@hrbmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200508
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Drug Combinations)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (long noncoding RNA HIF1A-AS2, human)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Coculture Techniques
MH  - Collagen/metabolism
MH  - Dental Pulp/cytology/*metabolism
MH  - Drug Combinations
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Human Umbilical Vein Endothelial Cells/*transplantation
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/metabolism
MH  - Laminin/metabolism
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mice
MH  - Neovascularization, Physiologic/*physiology
MH  - Proteoglycans/metabolism
MH  - RNA, Long Noncoding/genetics
MH  - Regeneration/physiology
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - Angiogenesis
OT  - Endothelial cells
OT  - HIF1A-AS2
OT  - Hif-1 signaling pathway
OT  - Human umbilical cord mesenchymal stem cells
OT  - Pulp regeneration
COIS- Declaration of competing interest The authors declare that they have no conflicts 
      of interest.
EDAT- 2020/05/12 06:00
MHDA- 2020/06/26 06:00
CRDT- 2020/05/12 06:00
PHST- 2019/12/17 00:00 [received]
PHST- 2020/04/30 00:00 [revised]
PHST- 2020/05/05 00:00 [accepted]
PHST- 2020/05/12 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2020/05/12 06:00 [entrez]
AID - S0024-3205(20)30511-7 [pii]
AID - 10.1016/j.lfs.2020.117763 [doi]
PST - ppublish
SO  - Life Sci. 2020 Aug 15;255:117763. doi: 10.1016/j.lfs.2020.117763. Epub 2020 May 
      8.