Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium.
BACKGROUND
Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy.


HYPOTHESIS
Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues.


STUDY DESIGN
Controlled laboratory study.


METHODS
We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats.


RESULTS
Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo.


CONCLUSION
Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo.


CLINICAL RELEVANCE
To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA.
['Leijs|Maarten J C|MJ|', 'van Buul|Gerben M|GM|', 'Verhaar|Jan A N|JA|', 'Hoogduijn|Martin J|MJ|', 'Bos|Pieter K|PK|', 'van Osch|Gerjo J V M|GJ|']
D000368:Aged D000693:Anaerobiosis D000818:Animals D002356:Cartilage D002465:Cell Movement D002630:Chemotactic Factors D005260:Female D006801:Humans D018836:Inflammation Mediators D007270:Injections, Intra-Articular D008297:Male D059630:Mesenchymal Stem Cells D008875:Middle Aged D020370:Osteoarthritis, Knee D010100:Oxygen D051381:Rats D017208:Rats, Wistar D013583:Synovial Membrane
mesenchymal stem cells migration osteoarthritis cell therapy inflammation