Heparin and Derivatives for Advanced Cell Therapies

International Journal of Molecular Sciences, 2021 · DOI: https://doi.org/10.3390/ijms222112041 · Published: November 7, 2021

Pharmacology Regenerative Medicine

Simple Explanation

Heparin and its derivatives are widely used to prevent and treat blood clots. While their anticoagulant effects are well-known, their impact on cell behavior and potential side effects are still being investigated. Heparins are now being explored in regenerative medicine for cell-based therapies and as components of functionalized matrices in biotechnology. The renewed interest in heparins stems from their potential to combat COVID-19 through a combination of anti-inflammatory, anti-thrombotic, and anti-viral actions. This review summarizes key information on heparins and their impact on cell therapeutics, emphasizing the importance of differentiating between different types of heparins. Heparins can act as modulators of key processes during cell adhesion, migration, communication, proliferation and differentiation in vitro and in vivo. The application of cell-based therapeutics often demands the in vitro use of UFH to support proliferation and/or differentiation of certain cell types.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
UFH, LMWH, and synthetic pentasaccharides are used to prevent and cure thromboembolic events, but UFH is also a modulator of cell adhesion, migration, communication, proliferation, and differentiation.
2
UFH is used in vitro to support cell proliferation and differentiation and is increasingly added to HPL-based cell cultures. It is also beneficial in vivo to prevent IBMIR and thromboembolic complications after transfusion of tissue factor-expressing stromal cells.
3
Heparins interact with bioactive molecules, leading to local concentration and conformational changes of proteins, affecting their target affinity and specificity. Understanding these interactions is crucial for designing cell-based therapies, especially considering the bleeding risk associated with UFH.

Research Summary

This review summarizes the impact for manufacturing and application of cell therapeutics and highlights the need for discriminating the different heparins. The most important clinical application of LMWH is prophylaxis and treatment of deep vein thrombosis, stroke and pulmonary embolism in medical and surgical patients A growing number of biotechnology applications is using heparins to support the production of speciﬁc cell-based therapeutics.

Practical Implications

Optimizing Cell-Based Therapies

A more detailed understanding and more precise reporting of the different heparin’s influence on cell biology is mandatory for the future design of cell-based therapies.

Managing Bleeding Risk

The bleeding risk associated with UFH use must be carefully considered in cell-based therapies.

Developing Heparin-Based Biomaterials

Heparins are attractive components of biomaterials aiming to support different aspects of regeneration.

Study Limitations

1
The risk of bleeding complications may hinder efficient therapy.
2
UFH is of porcine origin, there are still no alternative anticoagulants of human origin established for cell culture
3
Clinical trials comparing efﬁciency and safety of UFH, LMWH, pentasaccharides or oral anticoagulants for IBMIR prophylaxis are still missing.

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