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J Diabetes Res. 2017;2017:5649191. doi: 10.1155/2017/5649191. Epub 2017 Jul 3.

Proinsulin Promotes Self-Renewal of a Hematopoietic Progenitor Cell Line In Vitro.

Han Y1,2,3, Liu T1, Zou Y1,4, Ji L1, Li Y5, Li J1, Wang J1, Chen G2, Chen J4, Chen L6, Ye Z1,4.

Author information

1
Institute of Tropical Medicine, Third Military Medical University, Chongqing, China.
2
Bioengineering College, Chongqing University, Chongqing, China.
3
Xi'an Center for Disease Control and Prevention, Xi'an, China.
4
Department of Hematology, Southwest Hospital, Chongqing, China.
5
Biomedical Analysis Center, Third Military Medical University, Chongqing, China.
6
Department of Plastic and Aesthetic Surgery, Southwest Hospital, Chongqing, China.

Abstract

The objective of this study was to assess the effects of exogenously expressed proinsulin on the biological characters of a hematopoietic stem cell line (HSC) and erythroid myeloid lymphoid (EML) cells and explore new strategies for cell therapy for type I diabetes. EML cells were transduced with lentivirus particles carrying the human proinsulin (proINS) gene. The positive transduced cells were selected based on green fluorescence protein (GFP) positivity and puromycin resistance. Overexpression of proINS was confirmed via real-time PCR and Western blotting. The functional activity of the human proINS secreted by EML cells was elucidated by analyzing the activation of insulin receptor and its downstream signaling. Pro-INS + EML cells were able to prime the phosphorylation of insulin receptor as well as induce the expression of downstream genes of insulin receptor. Furthermore, Wnt3a can significantly promote self-renewal of Pro-INS + EML cells. However, we did not observe significant changes in the proliferation and differentiation of INS + EML cells, compared to the control EML cells. Our results might be useful for developing a new therapy for diabetes mellitus.

PMID:
28758130
PMCID:
PMC5512049
DOI:
10.1155/2017/5649191
[Indexed for MEDLINE]
Free PMC Article

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