Transient Proteolytic Modification of Mesenchymal Stromal Cells Increases Lung Clearance Rate and Targeting to Injured Tissue

This study showed that an alternative cell detachment of mesenchymal stromal/stem cells (MSCs) with pronase instead of trypsin significantly accelerated the lung clearance of the cells and, importantly, increased their targeting to an area of injury. Pronase detachment could be used as a method to i...

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Published in:	Stem cells translational medicine Vol. 2; no. 7; pp. 510 - 520
Main Authors:	Kerkelä, Erja, Hakkarainen, Tanja, Mäkelä, Tuomas, Raki, Mari, Kambur, Oleg, Kilpinen, Lotta, Nikkilä, Janne, Lehtonen, Siri, Ritamo, Ilja, Pernu, Roni, Pietilä, Mika, Takalo, Reijo, Juvonen, Tatu, Bergström, Kim, Kalso, Eija, Valmu, Leena, Laitinen, Saara, Lehenkari, Petri, Nystedt, Johanna
Format:	Journal Article
Language:	English
Published:	United States AlphaMed Press 01-07-2013 Oxford University Press
Subjects:	Administrative support Animals Antigens, Surface - metabolism Bioavailability Bone marrow stromal cells Carrageenan - toxicity Cell adhesion & migration Cell adhesion molecules Cell Differentiation - physiology Cell transplantation Cell- and Tissue-Based Therapy - methods Data analysis Data collection Disease Models, Animal Enabling Technologies for Cell-Based Clinical Translation Experimental models Graft Survival - physiology Humans Inflammation Inflammation - chemically induced Inflammation - immunology Inflammation - therapy Leukocyte Rolling - physiology Lung - cytology Lung - metabolism Lungs Mass spectrometry Mesenchymal Stem Cell Transplantation - methods Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Mesenchyme Mice Neovascularization, Physiologic - physiology Peptides Pronase Pronase - metabolism Proteins Proteolysis Rats Scientific imaging Stromal cells Swine T-Lymphocytes - cytology T-Lymphocytes - metabolism Trypsin Writing United Kingdom > UK Finland Bone marrow stromal cells Experimental models Cell transplantation Cell adhesion molecules Mesenchymal stem cells
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Summary:	This study showed that an alternative cell detachment of mesenchymal stromal/stem cells (MSCs) with pronase instead of trypsin significantly accelerated the lung clearance of the cells and, importantly, increased their targeting to an area of injury. Pronase detachment could be used as a method to improve the MSC lung clearance and targeting in vivo. This may have a major impact on the bioavailability of MSCs in future therapeutic regimes. Systemic infusion of therapeutic cells would be the most practical and least invasive method of administration in many cellular therapies. One of the main obstacles especially in intravenous delivery of cells is a massive cell retention in the lungs, which impairs homing to the target tissue and may decrease the therapeutic outcome. In this study we showed that an alternative cell detachment of mesenchymal stromal/stem cells (MSCs) with pronase instead of trypsin significantly accelerated the lung clearance of the cells and, importantly, increased their targeting to an area of injury. Cell detachment with pronase transiently altered the MSC surface protein profile without compromising cell viability, multipotent cell characteristics, or immunomodulative and angiogenic potential. The transient modification of the cell surface protein profile was sufficient to produce effective changes in cell rolling behavior in vitro and, importantly, in the in vivo biodistribution of the cells in mouse, rat, and porcine models. In conclusion, pronase detachment could be used as a method to improve the MSC lung clearance and targeting in vivo. This may have a major impact on the bioavailability of MSCs in future therapeutic regimes.
Bibliography:	Shared last authorship.
ISSN:	2157-6564 2157-6580
DOI:	10.5966/sctm.2012-0187