Competitive stem cell recruitment by multiple cytotactic cues.
A multitude of cytotactic cues direct cell migration in development, cancer metastasis and wound healing. However, our understanding of cell motility remains fragmented partially because current migration devices only allow the study of independent factors. We developed a cell motility assay that allows competitive recruitment of a given cell population simultaneously by gradients of multiple cytotactic cues, observable under real-time imaging. Well-defined uniform gradients of cytotactic cues can be independently generated and sustained in each channel. As a case study, bone marrow mesenchymal stem/stromal cells (MSCs) were exposed to 15 cytokines that are commonly present in arthritis. Cytokines that induced robust recruitment of MSCs in multiple groups were selected to 'compete' in a final round to yield the most chemotactic factor(s) based on cell migration numbers, distances, migration indices and motility over time. The potency of a given cytokine in competition frequently differed from its individual action, substantiating the need to test multiple cytokines concurrently due to synergistic or antagonistic effects. This new device has the rare capacity to screen molecules that induce cell migration in cancer therapy, drug development and tissue regeneration.
Tissue Engineering and Regenerative Medicine Laboratory (TERML), Columbia University Medical Center, 630 W. 168 St. - PH7E, New York, NY 10032, USA.
Avital
A
Mendelson
Yuk kee
Yk
Cheung
Kamila
K
Paluch
Mo
M
Chen
Kimi
K
Kong
Jiali
J
Tan
Ziming
Z
Dong
Samuel K
SK
Sia
Jeremy J
JJ
Mao
D001854:Bone Marrow Cells / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors; D016207:Cytokines / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D012685:Sepharose / Q000737:chemistry
D002630:Chemotactic Factors; D016207:Cytokines; D005456:Fluorescent Dyes; D012685:Sepharose