Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-28T02:40:13.672Z Has data issue: false hasContentIssue false
  • English
  • Français

Chemotaxis of Mesenchymal Stem Cells in a Microfluidic Device

Published online by Cambridge University Press:  20 December 2012

Ruth Choa ,
Manav Mehta ,
Kangwon Lee  and
David Mooney
Ruth Choa
Affiliation:
School of Engineering and Applied Sciences, Harvard University, Cambridge MA, 02138
Manav Mehta
Affiliation:
School of Engineering and Applied Sciences, Harvard University, Cambridge MA, 02138
Kangwon Lee
Affiliation:
School of Engineering and Applied Sciences, Harvard University, Cambridge MA, 02138
David Mooney
Affiliation:
School of Engineering and Applied Sciences, Harvard University, Cambridge MA, 02138
Get access

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.

Keywords

biologicalbiomedicalfluidics
Type
Articles
Information
MRS Online Proceedings Library (OPL) , Volume 1498: Symposium L – Biomimetic, Bio-inspired and Self-Assembled Materials for Engineered Surfaces and Applications , 2013 , pp. 67 - 72
Copyright
Copyright © Materials Research Society 2012 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Nardi, N and da Silva, Meirelles L, 2006, Mesenchymal stem cells: isolation, in vitro expansion and characterization, Stem Cells, v. 174, 249–82.CrossRefGoogle Scholar
Wakitani, S, Nawata, M, et al. , 2007, Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation, Journal of Tissue Engineering and Regenerative Medicine, v. 1, 74–9.CrossRefGoogle ScholarPubMed
Kruidenier, L, MacDonald, TT, et al. , 2006, Myofirboblast matrix metalloproteinases activate the neutrophil chemoattractant CXCL7 from intestinal rpithelial cells, Gastroenterology, v. 130, 127–36.CrossRefGoogle ScholarPubMed
Balabanian, et al. , 2005, SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes, J Biol Chem, v. 280, 35760–6.CrossRefGoogle ScholarPubMed
Rosenkilde, MM, Gerlach, LO, Jakobsen, JS, et al. ., 2004, Molecular mechanism of AMD 3100 antagonism in the CXCR4 receptor, J Biochem, 279(4):3033–41.Google ScholarPubMed
Kalwitz, G, Endres, M, Neumann, K, et al. ., 2009, Gene expression profile of adult human bone marrow derived mesenchymal stem cells stimulated by the chemokine CXCL7, J Biochem Cell Bio, 41(3): 649–58CrossRefGoogle ScholarPubMed
Kitaori, T, Schwarz, EM, Tsutsumi, R, et al. , 2009, Stromal cell derived factor 1/ CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model., Arthirits Rheum, 60(3): 813–23.CrossRefGoogle ScholarPubMed
Sudong, K, Hyung, JK, Jeon, NL, 2010, Biological applications of microfluidic gradient devices, Integr. Biol, 2: 584–603.Google Scholar
Tang, S, and Whitesides, G, 2009, Basic microfluidic and soft lithography techniques, Optofluidics: Fundamentals, Devices, and Applications. Google Scholar
Jeon, N, Baskaran, H, Dertinger, S, et al. , 2002, Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device, Nature Biotechnology,20(8):836–30.Google Scholar
Whitesides, G, Ostuni, E, Takayama, S, et al. , 2001, Soft lithography in biology and biochemistry, Annu. Rev. Biomed. Eng., 3: 335–73.CrossRefGoogle ScholarPubMed
Zengel, P, Nyugen-Hoang, A, Schildhammer, C, 2011, u-Slide chemotaxis: a new chamber for long term chemotaxis studies, BMC Cell Biology, 12(1): 21.CrossRefGoogle ScholarPubMed
McKibbin, B,1978, The biology of fracture healing in long bones. Journal of Bone and Joint Surgery, 60(2):150–62.CrossRefGoogle ScholarPubMed
Chen, L, Tredget, EE, Wu, PY, Wu, Y, 2008, Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One, 3(4):31886.Google ScholarPubMed
Mehta, M et al. , 2012, Biomaterial delivery of morphogens to mimic the natural healing cascade in bone. Adv. Drug Deliv. Rev. 64(12): 1257–76CrossRefGoogle ScholarPubMed
Romagnani, P., Lasagni, L., Annunziato, F., Serio, M., Romagnani, S., 2004, CXC chemokines: the regulatory link between inflammation and angiogenesis, Trends Immunol,25(4):201–9.CrossRefGoogle ScholarPubMed
Kryczek, I., Wei, S., Keller, E., Liu, R., Zou, W., 2007, Stromal-derived factor (SDF-1/CXCL12) and human tumor pathogenesis., Am. J. Physiol., Cell Physiol. 292 (3): C987–95.CrossRefGoogle Scholar