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  4. Heparin Differentially Impacts Gene Expression of Stromal Cells from Various Tissues

Heparin Differentially Impacts Gene Expression of Stromal Cells from Various Tissues

Scientific Reports, 2019 · DOI: 10.1038/s41598-019-43700-x · Published: May 13, 2019

Regenerative MedicineGenetics

Simple Explanation

This study investigates how heparin, a common anticoagulant, affects stromal cells derived from different tissues: bone marrow (BM), umbilical cord (UC), and white adipose tissue (WAT). Stromal cells are important for tissue repair and are being tested for various therapies. The research found that heparin is taken up differently by stromal cells depending on their tissue origin, with BM and UC cells internalizing more heparin than WAT cells. This uptake influences the expression of various genes involved in cell functions like proliferation and adhesion. Despite these changes in gene expression, heparin did not significantly affect the long-term growth or differentiation potential of these stromal cells. This suggests that using heparin in cell culture for therapeutic purposes may be acceptable.

Study Duration
Not specified
Participants
3 donors each of bone marrow (BM), umbilical cord (UC) and white adipose tissue (WAT)
Evidence Level
Not specified

Key Findings

  • 1
    Heparin is internalized by stromal cells in a tissue-dependent manner, with BM- and UC-derived cells internalizing significantly more heparin than WAT-derived cells.
  • 2
    Heparin influences gene expression in stromal cells differently depending on the cell source, affecting genes involved in cell signaling, adhesion, inflammation, and angiogenesis.
  • 3
    Despite alterations in gene and protein expression, heparin does not substantially affect the long-term proliferation or in vitro differentiation of stromal cells.

Research Summary

The study aimed to investigate the influence of heparin on stromal cells derived from bone marrow (BM), umbilical cord (UC), and white adipose tissue (WAT), focusing on cellular uptake, gene expression, protein profiles, and biological properties. Results showed that heparin is internalized by stromal cells in a tissue-dependent manner and differentially regulates gene expression, impacting pathways related to proliferation, cell adhesion, inflammation, and angiogenesis. Despite these effects, heparin did not significantly alter the long-term proliferation or in vitro differentiation of stromal cells, suggesting its compatibility for clinical applications involving cell products.

Practical Implications

Cell Therapy Manufacturing

The findings suggest that heparin, commonly used in cell culture media to prevent clotting, does not significantly interfere with the manufacturing of stromal cell-based medicinal products.

Tissue-Specific Responses

The study highlights the importance of considering tissue-specific responses to heparin when studying or utilizing stromal cells from different origins.

Signaling Pathway Modulation

The identification of specific signaling pathways (WNT, PDGF, NOTCH, TGFbeta) affected by heparin provides potential targets for further research and manipulation of stromal cell behavior.

Study Limitations

  • 1
    Cellular internalization of F-heparin in lysosomes was tissue-dependent but expression of the corresponding HARE on stromal cell surface has not been shown so far.
  • 2
    Baseline gene expression of primary naïve stromal cells in the BM, UC or WAT before in vitro expansion would be a more precise control for analysis of gene alterations induced by heparin exposition.
  • 3
    due to low frequency in primary tissue samples a valid analysis was not possible in this study.

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