Chemotaxis of Mesenchymal Stem Cells in a Microfluidic Device
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Chemotaxis of Mesenchymal Stem Cells in a Microfluidic Device Ruth Choa, Manav Mehta, Kangwon Lee, and David Mooney School of Engineering and Applied Sciences, Harvard University Cambridge MA, 02138 ABSTRACT Adult bone marrow derived mesenchymal stem cells (MSCs) represent an important source of cells for tissue regeneration. Control of MSC migration and homing is still unclear. The goal of this study was to identify potent chemoattractants for MSCs and characterize MSC chemotaxis using a microfluidic device as a model system and assay platform. The three chemokines compared in this study were CXCL7, CXCL12, and AMD 3100. Microfluidic devices made of polydimethysiloxane (PDMS) were fabricated by soft lithography techniques and designed to generate a stable linear chemokine gradient. Cell movements in response to the gradient were captured by timelapse photos and tracked over 24 hours. Chemokine potency was measured via several chemotaxis parameters including: velocity in the direction of interest (V), center of mass (Mend), forward migration indice (YFMI). The migratory paths of the cells were mapped onto a displacement plot and compared. The following results were measured in the direction of interest (towards higher concentrations of chemokine): For velocity, only cells exposed to CXCL12 had a statistically significant (p=.014) average velocity (V=0.19 ± 0.07 um/min) when compared to the control condition (V=0.06 ±0 .04 um/min). For the center of mass, where the displacement of cells from their starting positions were compared, again only CXCL12 (Mend= 53.9 ± 10.8 um) stimulated statistically significant (p = .013) displacement of cells compared to the control condition (Mend = 19.3 ± 16.1 um). For the forward migration index, the efficiency of cell movement was measured. Indices in both the CXCL12 (YFIM = 0.19 ± 0.08) and CXCL7 (YFIM = 0.09 ±0.03) conditions were statistically significant (p = .023 for CXCL12 and p = .035 for CXCL7) when compared with the control index (YFIM = .04 ± .02). This study demonstrated the use of microfluidic devices as a viable platform for chemotaxis studies. A stable linear chemokine gradient was maintained over a long time scale to obtain cell migration results. CXCL12 was quantitatively determined to be the most potent chemoattractant in this research; these chemoattractive properties promote its use in future developments to control MSC homing. INTRODUCTION Bone marrow derived mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into osteoblasts, chondrocytes, and adipocytes.1 Directly transplanting or intravenously injecting MSCs into wound sites has been shown to be clinically successful in improving wound healing of bony tissues2. The migration and homing behavior of these cells can be affected by exposure to various chemokines. The CXC cytokines are a family of chemokines known to induce chemotaxis in a variety of cell types. There are currently 17 known CXC ligands (CXCL1 through CXCL17) and 7 known CXC chemokine receptors (CXCR1 through CXCR7).
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