PMID- 24444073
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20220317
IS  - 1757-2215 (Print)
IS  - 1757-2215 (Electronic)
IS  - 1757-2215 (Linking)
VI  - 7
DP  - 2014 Jan 20
TI  - Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord 
      mesenchymal stem cells in nude mice.
PG  - 8
LID - 10.1186/1757-2215-7-8 [doi]
AB  - BACKGROUND: The human umbilical cord mesenchymal stem cells (hUCMSCs) have the 
      ability to migrate into tumors and therefore have been considered as an 
      alternative source of mesenchymal progenitors for the therapy of malignant 
      diseases. The present study was aimed to investigate effect of hUCMSCs as 
      vehicles for a constant source of transgenic interleukin-21 (IL-21) on ovarian 
      cancer in vivo. METHODS: The hUCMSCs were engineered to express IL-21 via 
      lentiviral vector- designated 'hUCMSCs-LV-IL-21', and then were transplanted into 
      SKOV3 ovarian cancer xenograft-bearing nude mice. The therapeutic efficacy and 
      mechanisms of this procedure on ovarian cancer was evaluated. RESULTS: The 
      isolated hUCMSCs were induced to differentiate efficiently into osteoblast and 
      adipocyte lineages in vitro. The expressed IL-21 in the supernatant from 
      hUCMSCs-LV-IL-21 obviously stimulated splenocyte's proliferation. The 
      hUCMSCs-LV-IL-21 significantly reduced SKOV3 ovarian cancer burden in mice 
      indicated by tumor sizes compared with control mice. The expressed IL-21 not only 
      regulated the levels of IFN-gamma and TNF-alpha in the mouse serum but also increased the 
      expression of NKG2D and MIC A molecules in the tumor tissues. The down regulation 
      of beta-catenin and cyclin-D1 in the tumor tissues may refer to the inhibition of 
      SKOV3 ovarian cancer growth in mice. In addition, hUCMSCs did not form gross or 
      histological teratomas up to 60 days posttransplantation in murine lung, liver, 
      stomach and spleen. CONCLUSION: These results clearly indicate a safety and 
      usability of hUCMSCs-LV- IL-21 in ovarian cancer gene therapy, suggesting the 
      strategy may be a promising new method for clinical treatment of ovarian cancer.
FAU - Zhang, Yunxia
AU  - Zhang Y
FAU - Wang, Jing
AU  - Wang J
FAU - Ren, Mulan
AU  - Ren M
AD  - Department of Gynecology & Obstetrics, Zhongda Hospital, Medical School, 
      Southeast University, Nanjing 210009, China. renmulan@seu.edu.cn.
FAU - Li, Miao
AU  - Li M
FAU - Chen, Dengyu
AU  - Chen D
FAU - Chen, Junsong
AU  - Chen J
FAU - Shi, Fangfang
AU  - Shi F
FAU - Wang, Xiaoying
AU  - Wang X
FAU - Dou, Jun
AU  - Dou J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140120
PL  - England
TA  - J Ovarian Res
JT  - Journal of ovarian research
JID - 101474849
RN  - 0 (CCND1 protein, human)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Interleukins)
RN  - 0 (beta Catenin)
RN  - 136601-57-5 (Cyclin D1)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - *Cord Blood Stem Cell Transplantation
MH  - Cyclin D1/metabolism
MH  - Female
MH  - Fetal Blood/*cytology
MH  - Genetic Therapy/*methods
MH  - HEK293 Cells
MH  - Humans
MH  - Interleukins/*biosynthesis/genetics
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Ovarian Neoplasms/genetics/metabolism/*therapy
MH  - Time Factors
MH  - Tumor Burden
MH  - Wnt Signaling Pathway
MH  - Xenograft Model Antitumor Assays
MH  - beta Catenin/metabolism
PMC - PMC3909346
EDAT- 2014/01/22 06:00
MHDA- 2014/01/22 06:01
PMCR- 2014/01/20
CRDT- 2014/01/22 06:00
PHST- 2013/12/04 00:00 [received]
PHST- 2014/01/16 00:00 [accepted]
PHST- 2014/01/22 06:00 [entrez]
PHST- 2014/01/22 06:00 [pubmed]
PHST- 2014/01/22 06:01 [medline]
PHST- 2014/01/20 00:00 [pmc-release]
AID - 1757-2215-7-8 [pii]
AID - 10.1186/1757-2215-7-8 [doi]
PST - epublish
SO  - J Ovarian Res. 2014 Jan 20;7:8. doi: 10.1186/1757-2215-7-8.