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Updated: Jun 22, 2026

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Settings and mechanisms for trans-cellular diapedesis.
Peter T Sage1, Christopher V Carman
1Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Leukocyte diapedesis, or cell crossing of endothelial barriers, occurs via paracellular and transcellular routes. Recent in vitro data support the transcellular pathway, prompting a reevaluation of its in vivo significance.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Immune cell function relies on leukocyte trafficking and diapedesis across endothelial barriers.
- Two migratory pathways, paracellular and transcellular, have been proposed for diapedesis.
- The transcellular pathway lacked in vitro validation, hindering its acceptance.
Purpose of the Study:
- To reevaluate the physiological roles and mechanisms of the transcellular diapedesis pathway.
- To integrate emerging in vitro findings with existing in vivo observations.
- To provide a comprehensive framework for understanding transcellular diapedesis.
Main Methods:
- Review and synthesis of existing in vivo literature on leukocyte diapedesis.
- Integration of recent in vitro studies demonstrating transcellular migration.
- Comparative analysis of paracellular versus transcellular pathways in various physiological and inflammatory settings.
Main Results:
- In vitro studies now provide unambiguous evidence for transcellular diapedesis.
- A substantial body of in vivo evidence supports significant utilization of the transcellular pathway.
- The transcellular route is observed in both constitutive trafficking (bone marrow, lymphoid organs) and inflammatory extravasation.
Conclusions:
- The transcellular route of leukocyte diapedesis is a physiologically relevant pathway.
- Renewed interest in transcellular diapedesis is supported by both in vitro and in vivo data.
- Understanding the transcellular pathway is crucial for comprehending immune cell trafficking and inflammatory responses.
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