Dextran induces differentiation of circulating endothelial progenitor cells
Syotaro Obi1, Haruchika Masuda, Hiroshi Akimaru
1Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Japan.
Physiological Reports
|April 25, 2014
Summary
Dextran promotes the differentiation of circulating endothelial progenitor cells (EPCs) into adhesive cells, enhancing their therapeutic potential for cardiovascular diseases by improving adhesion, proliferation, and tube formation.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Regenerative Medicine
Background:
- Endothelial progenitor cells (EPCs) show promise for cardiovascular disease treatment.
- The differentiation of circulating EPCs into adhesive forms is not well understood.
- Circulating EPCs typically exhibit poor attachment in standard cultures.
Purpose of the Study:
- To investigate if immature circulating EPCs can differentiate into mature, adhesive EPCs.
- To explore the role of dextran in promoting EPC differentiation and attachment.
- To elucidate the molecular mechanisms underlying dextran-induced EPC differentiation.
Main Methods:
- Culturing ex vivo expanded human cord blood EPCs with varying concentrations of dextran (5% and 10%).
- Assessing EPC bioactivities including adhesion, proliferation, migration, and tube formation.
- Analyzing surface protein expression of endothelial markers and quantifying mRNA levels of relevant genes.
- Investigating the involvement of specific signal transduction pathways (PI3K/Akt, ERK1/2, JNK, p38) using inhibitor analysis.
Main Results:
- Dextran treatment significantly increased EPC adhesion to fibronectin-coated dishes and promoted exponential growth.
- Enhanced bioactivities (adhesion, proliferation, migration, tube formation) and increased expression of endothelial markers were observed.
- Upregulation of endothelium-related genes and transcription factors, alongside downregulation of hematopoietic and antiangiogenic factors, was noted.
- PI3K/Akt, ERK1/2, JNK, and p38 signaling pathways were identified as crucial for dextran-induced differentiation.
Conclusions:
- Dextran effectively induces the differentiation of circulating EPCs, improving their adhesion, migration, proliferation, and vasculogenesis capabilities.
- The differentiation process is mediated by multiple signaling pathways, including PI3K/Akt, ERK1/2, JNK, and p38.
- Dextran represents a promising therapeutic agent for enhancing EPC function in regenerative medicine applications for cardiovascular diseases.
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