Controlled architectural and chemotactic studies of 3D cell migration.
Chemotaxis plays a critical role in tissue development and wound repair, and is widely studied using ex vivo model systems in applications such as immunotherapy. However, typical chemotactic models employ 2D systems that are less physiologically relevant or use end-point assays, that reveal little about the stepwise dynamics of the migration process. To overcome these limitations, we developed a new model system using microfabrication techniques, sustained drug delivery approaches, and theoretical modeling of chemotactic agent diffusion. This model system allows us to study the effects of 3D architecture and chemotactic agent gradient on immune cell migration in real time. We find that dendritic cell migration is characterized by a strong interplay between matrix architecture and chemotactic gradients, and migration is also influenced dramatically by the cell activation state. Our results indicate that Lipopolysaccharide-activated dendritic cells studied in a traditional transwell system actually exhibit anomalous migration behavior. Such a 3D ex vivo system lends itself for analyzing cell migratory behavior in response to single or multiple competitive cues and could prove useful in vaccine development.
School of Engineering and Applied Sciences, Harvard University, 9 Oxford Street, Cambridge, MA 02138, United States.
Prakriti
P
Tayalia
Eric
E
Mazur
David J
DJ
Mooney
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D055616:Microtechnology / Q000379:methods*; D008954:Models, Biological; D051381:Rats; D015398:Signal Transduction; D054457:Tissue Scaffolds / Q000737:chemistry
D018925:Chemokines
J Cell Sci. 1991 Aug;99 ( Pt 4):769-75
1770004
J Exp Med. 1973 Feb 1;137(2):387-410
4568301
Immunol Rev. 2000 Oct;177:134-40
11138771
Acta Oncol. 2002;41(2):124-30
12102155
J Control Release. 2008 Dec 18;132(3):273-8
18674579
J Cell Biol. 1989 Mar;108(3):973-84
2537839
Expert Opin Biol Ther. 2006 May;6(5):485-98
16610978
Nat Mater. 2009 Feb;8(2):151-8
19136947
J Cell Sci. 1981 Dec;52:1-10
7037797
Immunology. 2004 Jun;112(2):301-9
15147573
Vascular. 2007 Nov-Dec;15(6):350-5
18053419
Blood. 2002 Aug 15;100(4):1362-72
12149219
J Immunol. 1975 Dec;115(6):1650-6
1102606
J Immunol Methods. 1995 Mar 27;180(2):193-211
7714334
Nature. 1998 Mar 19;392(6673):245-52
9521319
J Immunol. 1998 Aug 1;161(3):1083-6
9686565
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14347-52
18794520
Cell. 1999 Oct 1;99(1):23-33
10520991
Biomaterials. 2008 Sep;29(27):3671-82
18565578
Lab Chip. 2005 Jun;5(6):611-8
15915253
FEBS Lett. 1998 Nov 27;440(1-2):188-94
9862452
J Immunol Methods. 1999 Feb 1;223(1):77-92
10037236
J Cell Biochem. 2009 Oct 15;108(3):537-46
19681040
Cell. 1988 Jul 1;54(1):83-93
3383244
J Cell Biol. 1977 Nov;75(2 Pt 1):606-16
264125
Biotechnol Bioeng. 2005 Sep 20;91(6):754-9
15981274
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2494-9
16477029
J Exp Med. 1962 Mar 1;115:453-66
13872176
Spine (Phila Pa 1976). 2002 Nov 1;27(21):2396-408
12438990
J Immunol. 1998 Sep 15;161(6):3096-102
9743376
Blood. 2002 Aug 15;100(4):1354-61
12149218
Neuroscience. 2001;103(3):831-40
11274797
J Immunol Methods. 1998 Jul 1;216(1-2):139-53
9760220