PMID- 25251668
OWN - NLM
STAT- MEDLINE
DCOM- 20150324
LR  - 20150113
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Linking)
VI  - 55
IP  - 1
DP  - 2015 Jan
TI  - Bone marrow stromal cells transduced with a thrombopoietin, interleukin-6, and 
      interleukin-11 syncretic gene induce cord mononuclear cells to generate platelets 
      in vitro.
PG  - 176-86
LID - 10.1111/trf.12800 [doi]
AB  - BACKGROUND: The induction of hematopoietic stem cells to produce mass numbers of 
      platelets (PLTs) in vitro is an effective method to address a lack of PLTs and 
      PLT transfusion resistance in the clinic. However, the design of a low-cost and 
      sustainable culture system is currently problematic. STUDY DESIGN AND METHODS: 
      Here, the thrombopoietin, interleukin (IL)-6, and IL-11 genes, three regulatory 
      factors important for thrombopoiesis, were used to construct self-splicing fusion 
      genes linked by foot and mouth disease (F2A) and Theiler's murine encephalitis 
      (T2A) viruses. Bone marrow stromal cells (BMSCs) transduced with the fusion gene 
      acted as nourishing cells and induced cord blood mononuclear cells (MNCs) to 
      generate PLTs in vitro. We counted these cells; determined the percentage of 
      cells expressing specific cell surface markers (CD41); and measured their ability 
      to aggregate via flow cytometry, immunohistochemical staining, and aggregation 
      remote analyzer. RESULTS: BMSCs transduced with the fusion gene successfully 
      induced cord blood MNCs to generate PLT-sized fragments in the absence of 
      exogenous cytokines. The output was higher than that of the control groups, and 
      the PLT-sized fragments were similar to endogenous PLTs in terms of shape, CD41 
      expression, and aggregation function. CONCLUSION: These results suggest that our 
      method could be used to develop a low-cost sustainable cultivation system that 
      generates PLTs in vitro by enhancing the autocrine production of related 
      cytokines through the nourishment provided by cells transduced with a syncretic 
      gene.
CI  - (c) 2014 AABB.
FAU - Lu, Hua
AU  - Lu H
AD  - Transfusion Department, Southwest Hospital Third Military Medical University, 
      Chongqing, China.
FAU - Jiang, Tianlun
AU  - Jiang T
FAU - Li, Ruqing
AU  - Li R
FAU - Wang, Shichun
AU  - Wang S
FAU - Zhang, Qiang
AU  - Zhang Q
FAU - Zhao, Shuming
AU  - Zhao S
LA  - eng
SI  - GENBANK/F01310
SI  - GENBANK/F01370
SI  - GENBANK/F02850
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140923
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (IL11 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-11)
RN  - 0 (Interleukin-6)
RN  - 9014-42-0 (Thrombopoietin)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Base Sequence
MH  - Blood Platelets/*cytology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fetal Blood/*cytology
MH  - Flow Cytometry
MH  - Foot-and-Mouth Disease Virus/genetics
MH  - *Genes, Synthetic
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Interleukin-11/genetics/*metabolism
MH  - Interleukin-6/genetics/*metabolism
MH  - Leukocytes, Mononuclear/*cytology
MH  - Molecular Sequence Data
MH  - Protein Biosynthesis
MH  - Stromal Cells/*cytology/metabolism
MH  - Theilovirus/genetics
MH  - *Thrombopoiesis
MH  - Thrombopoietin/genetics/*metabolism
MH  - Transduction, Genetic
EDAT- 2014/09/25 06:00
MHDA- 2015/03/25 06:00
CRDT- 2014/09/25 06:00
PHST- 2014/01/15 00:00 [received]
PHST- 2014/05/16 00:00 [revised]
PHST- 2014/05/23 00:00 [accepted]
PHST- 2014/09/25 06:00 [entrez]
PHST- 2014/09/25 06:00 [pubmed]
PHST- 2015/03/25 06:00 [medline]
AID - 10.1111/trf.12800 [doi]
PST - ppublish
SO  - Transfusion. 2015 Jan;55(1):176-86. doi: 10.1111/trf.12800. Epub 2014 Sep 23.