Selection of Tissue Factor-Deficient Cell Transplants as a Novel Strategy for Improving Hemocompatibility of Human Bone Marrow Stromal Cells

Theranostics, 2018 · DOI: 10.7150/thno.21906 · Published: February 4, 2018

Cardiovascular Science Regenerative Medicine Biomedical

Simple Explanation

Intravascular transplantation of cells that carry tissue factor (TF) can cause an immediate inflammatory reaction in the blood, leading to blood clots and hindering successful transplantation. The study found that bone marrow stromal cells (BMSC) have a subpopulation with less TF expression, resulting in reduced pro-coagulant activity. In contrast, cells from umbilical cord (UC) and white adipose tissue (WAT) showed high TF expression and clot formation. Selecting BMSCs that lack TF is a new approach to make cell therapy safer by lowering the risk of blood clot formation.

Study Duration

Not specified

Participants

Healthy volunteers and patients undergoing liposuctions

Evidence Level

Level: Not specified, Study type: In vitro and in vivo experiments

Key Findings

1
Bone marrow stromal cells (BMSCs) exhibit significantly lower tissue factor (TF) expression compared to white adipose tissue (WAT) and umbilical cord (UC) stromal cells.
2
Depletion of TF/CD142+ subpopulation in BMSCs significantly improved hemocompatibility without affecting immunomodulation.
3
Selecting TF-deficient BMSCs significantly diminishes IBMIR risk without affecting their immunomodulatory potential In Vitro.

Research Summary

This study investigates the hemocompatibility of human white adipose tissue (WAT), umbilical cord (UC), and bone marrow stromal cells (BMSC) for safer cell transplantation. The study demonstrates that plasma-based thromboelastometry is a reliable tool for detecting pro-coagulant activity of therapeutic cells and selecting TF-deficient BMSC is a novel strategy for improving cell therapy applicability. The research concludes that selecting tissue factor (TF)-deficient bone marrow stromal cells (BMSCs) improves hemocompatibility and reduces the risk of instant blood-mediated inflammatory reaction (IBMIR).

Practical Implications

Improved Cell Therapy Safety

Selecting TF-deficient BMSCs can improve the safety of cell therapies by reducing the risk of IBMIR and thromboembolic events.

Enhanced Cell Engraftment

By reducing IBMIR, TF-deficient BMSCs may lead to improved cell engraftment and therapeutic efficacy.

Refined Cell Source Selection

The study highlights the importance of considering the pro-coagulant properties of different stromal cell sources when designing cell therapies.

Study Limitations

1
Confirming differences in pro-coagulant activity in a clinically relevant (e.g., humanized) model in vivo would be desirable.
2
The precise display of complement activation by therapeutic cells in our assay format may need to be validated in advance of implementation as a safety measure for therapeutic cells.
3
We focused on testing standardized plasma thromboelastometry as readout for directly comparing the pro-coagulant effect of the TF/CD142± therapeutic cells in this study.

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