title: Engineering approaches toward deconstructing and controlling the stem cell environment.
abstract: Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e., the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. In this article, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Partners Research Building, Room 252, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Faramarz
authors.initials: F
authors.lastname: Edalat
authors.forename: Hojae
authors.initials: H
authors.lastname: Bae
authors.forename: Sam
authors.initials: S
authors.lastname: Manoucheri
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Cha
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D032701:Biomimetics / Q000295:instrumentation / Q000379:methods; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods; D012038:Regeneration; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
references.citation: Science. 2006 Mar 31;311(5769):1880-5
references.pmid: 16574858
references.citation: Am J Physiol Heart Circ Physiol. 2005 Apr;288(4):H1915-24
references.pmid: 15576436
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2480-7
references.pmid: 16477028
references.citation: Integr Biol (Camb). 2009 Mar;1(3):235-41
references.pmid: 20023734
references.citation: Annu Rev Biophys. 2011;40:361-78
references.pmid: 21391812
references.citation: Nat Mater. 2010 Jan;9(1):82-8
references.pmid: 19838182
references.citation: Nat Mater. 2010 Jun;9(6):518-26
references.pmid: 20418863
references.citation: Chem Commun (Camb). 2005 Jan 21;(3):331-3
references.pmid: 15645027
references.citation: Can J Chem Eng. 2010 Dec;88(6):899-911
references.pmid: 21874065
references.citation: Exp Cell Res. 2007 Aug 15;313(14):3066-75
references.pmid: 17524393
references.citation: Dev Cell. 2004 Apr;6(4):483-95
references.pmid: 15068789
references.citation: J R Soc Interface. 2009 Jun 6;6 Suppl 3:S341-8
references.pmid: 19106069
references.citation: Cell. 2008 Feb 22;132(4):598-611
references.pmid: 18295578
references.citation: Nat Biotechnol. 2010 Oct;28(10):1123-8
references.pmid: 20890282
references.citation: Biomaterials. 2009 May;30(13):2507-15
references.pmid: 19162317
references.citation: Science. 2010 Jul 30;329(5991):538-41
references.pmid: 20576850
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9522-7
references.pmid: 18599452
references.citation: Nat Methods. 2005 Feb;2(2):119-25
references.pmid: 15782209
references.citation: Langmuir. 2002 Apr 2;18(7):2459-62
references.pmid: 12088033
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14347-52
references.pmid: 18794520
references.citation: Science. 1997 May 30;276(5317):1425-8
references.pmid: 9162012
references.citation: Biotechniques. 2010 Apr;48(4):ix-xxii
references.pmid: 20569203
references.citation: Cell. 2004 Mar 19;116(6):769-78
references.pmid: 15035980
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: Curr Opin Biotechnol. 2011 Oct;22(5):667-73
references.pmid: 21419621
references.citation: EMBO J. 2007 Nov 14;26(22):4744-55
references.pmid: 17948051
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3299-304
references.pmid: 19820164
references.citation: Nanomedicine (Lond). 2010 Apr;5(3):469-84
references.pmid: 20394538
references.citation: Science. 1998 Nov 6;282(5391):1145-7
references.pmid: 9804556
references.citation: Science. 2005 Nov 18;310(5751):1135-8
references.pmid: 16293749
references.citation: Nat Med. 2010 Jul;16(7):814-20
references.pmid: 20543851
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2130-5
references.pmid: 19179282
references.citation: Trends Biotechnol. 2003 Apr;21(4):157-61
references.pmid: 12679063
references.citation: Nat Methods. 2008 Jul;5(7):645-50
references.pmid: 18552855
references.citation: Nature. 2008 Sep 4;455(7209):85-8
references.pmid: 18769436
references.citation: Science. 2002 Mar 1;295(5560):1702-5
references.pmid: 11834780
references.citation: ACS Chem Biol. 2007 May 22;2(5):347-55
references.pmid: 17480050
references.citation: Nat Immunol. 2001 Feb;2(2):172-80
references.pmid: 11175816
references.citation: Biomacromolecules. 2003 May-Jun;4(3):713-22
references.pmid: 12741789
references.citation: Tissue Eng Part A. 2009 Feb;15(2):205-19
references.pmid: 18694293
references.citation: Adv Mater. 2009 Sep 4;21(32-33):3307-29
references.pmid: 20882499
references.citation: Biomaterials. 2008 Feb;29(6):752-63
references.pmid: 18001830
references.citation: Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):67-72
references.pmid: 21149682
references.citation: Exp Cell Res. 2007 May 15;313(9):1820-9
references.pmid: 17428465
references.citation: Langmuir. 2004 Jun 22;20(13):5153-6
references.pmid: 15986641
references.citation: Nat Med. 2008 Feb;14(2):213-21
references.pmid: 18193059
references.citation: Nat Mater. 2008 Mar;7(3):248-54
references.pmid: 18246072
references.citation: Nature. 2006 Jun 29;441(7097):1075-9
references.pmid: 16810242
references.citation: Nature. 2003 Oct 23;425(6960):836-41
references.pmid: 14574412
references.citation: Biomaterials. 2008 May;29(15):2348-58
references.pmid: 18313138
references.citation: Biomaterials. 2010 Oct;31(30):7836-45
references.pmid: 20667588
references.citation: Adv Mater. 2010 Dec 7;22(46):5276-81
references.pmid: 20941801
references.citation: Science. 2010 Aug 27;329(5995):1078-81
references.pmid: 20647425
references.citation: Cell Stem Cell. 2009 Jul 2;5(1):17-26
references.pmid: 19570510
references.citation: Cell Stem Cell. 2008 Jun 5;2(6):602-12
references.pmid: 18522853
references.citation: Nature. 2009 Nov 26;462(7272):433-41
references.pmid: 19940913
references.citation: Nat Med. 2011 Mar;17(3):313-9
references.pmid: 21386835
references.citation: Adv Mater. 2010 Jan 12;22(2):175-89
references.pmid: 20217683
references.citation: Cell. 2008 Feb 22;132(4):544-8
references.pmid: 18295571
references.citation: Tissue Eng. 2006 Sep;12(9):2695-706
references.pmid: 16995803
references.citation: Nature. 2009 Jun 25;459(7250):1131-5
references.pmid: 19440194
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11298-303
references.pmid: 17581871
references.citation: Dev Cell. 2003 Feb;4(2):241-51
references.pmid: 12586067
references.citation: Angew Chem Int Ed Engl. 2009;48(30):5406-15
references.pmid: 19492373
references.citation: Nat Mater. 2008 Oct;7(10):816-23
references.pmid: 18724374
references.citation: Nature. 2003 May 22;423(6938):409-14
references.pmid: 12717450
references.citation: Adv Drug Deliv Rev. 2008 Jan 14;60(2):215-28
references.pmid: 17997187
references.citation: Trends Biotechnol. 2009 Jun;27(6):342-9
references.pmid: 19398140
references.citation: Cell Stem Cell. 2009 Jun 5;4(6):507-10
references.pmid: 19497279
references.citation: Organogenesis. 2010 Oct-Dec;6(4):234-44
references.pmid: 21220962
references.citation: Nat Mater. 2009 Jun;8(6):457-70
references.pmid: 19458646
references.citation: Cell. 2006 Aug 25;126(4):677-89
references.pmid: 16923388
references.citation: Curr Opin Chem Biol. 2007 Aug;11(4):381-7
references.pmid: 17669680
references.citation: Nat Biotechnol. 2004 Jul;22(7):863-6
references.pmid: 15195101
references.citation: Nat Biotechnol. 2003 May;21(5):513-8
references.pmid: 12704396
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2494-9
references.pmid: 16477029
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16978-83
references.pmid: 19805103
references.citation: Lab Chip. 2007 Jun;7(6):786-94
references.pmid: 17538722
references.citation: JALA Charlottesv Va. 2010 Dec 1;15(6):440-448
references.pmid: 21344063
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12741-6
references.pmid: 14561891
references.citation: Nat Cell Biol. 2010 Jul;12(7):711-8
references.pmid: 20581838
references.citation: Lab Chip. 2005 Apr;5(4):401-6
references.pmid: 15791337
references.citation: Biomaterials. 2006 Nov;27(31):5391-8
references.pmid: 16828863
references.citation: Cell Stem Cell. 2011 Mar 4;8(3):252-61
references.pmid: 21362565
references.citation: Pharm Res. 2011 Jun;28(6):1422-30
references.pmid: 21331474
references.citation: Nat Methods. 2006 May;3(5):369-75
references.pmid: 16628207
references.citation: Cell. 2007 Oct 19;131(2):324-36
references.pmid: 17956733
references.citation: Acta Biomater. 2011 Mar;7(3):1249-64
references.pmid: 21074640
references.citation: Mol Syst Biol. 2006;2:37
references.pmid: 16820778
references.citation: Cell Stem Cell. 2010 Feb 5;6(2):103-15
references.pmid: 20144784
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2586-91
references.pmid: 18272481
references.citation: Circulation. 2005 Feb 1;111(4):442-50
references.pmid: 15687132
references.citation: Nat Biotechnol. 2001 Nov;19(11):1029-34
references.pmid: 11689847
references.citation: Adv Drug Deliv Rev. 2008 Jun 10;60(9):958-70
references.pmid: 18406491
references.citation: Macromol Biosci. 2009 Mar 10;9(3):221-9
references.pmid: 19089870
references.citation: Nature. 1978 Jun 1;273(5661):345-9
references.pmid: 661946
references.citation: Nat Methods. 2009 Feb;6(2):147-52
references.pmid: 19122668
references.citation: Nature. 2010 Jan 28;463(7280):485-92
references.pmid: 20110992
references.citation: Biomacromolecules. 2002 Mar-Apr;3(2):232-8
references.pmid: 11888306
references.citation: Nature. 2006 Jul 27;442(7101):368-73
references.pmid: 16871203
references.citation: Transplantation. 2011 Jun 27;91(12):1310-7
references.pmid: 21505379
references.citation: Biotechnol Prog. 2009 Jan-Feb;25(1):52-60
references.pmid: 19205022
references.citation: Lab Chip. 2010 Sep 21;10(18):2411-8
references.pmid: 20664846
references.citation: Lab Chip. 2008 Jan;8(1):34-57
references.pmid: 18094760
references.citation: Biomaterials. 2008 Jun;29(17):2608-15
references.pmid: 18358527
references.citation: Nature. 2005 Apr 28;434(7037):1134-8
references.pmid: 15858575
references.citation: Nat Methods. 2010 Sep;7(9):733-6
references.pmid: 20676108
references.citation: Cell Stem Cell. 2008 Mar 6;2(3):205-13
references.pmid: 18371446
references.citation: Nat Methods. 2011 May 22;8(7):581-6
references.pmid: 21602799
references.citation: Expert Opin Biol Ther. 2007 Aug;7(8):1123-7
references.pmid: 17696812
references.citation: Ann Biomed Eng. 2006 Jan;34(1):89-101
references.pmid: 16525765
references.citation: Biophys J. 2008 Nov 1;95(9):4426-38
references.pmid: 18658232
references.citation: Stem Cells. 2009 Nov;27(11):2646-54
references.pmid: 19711444
references.citation: Science. 2009 Jun 26;324(5935):1673-7
references.pmid: 19556500
references.citation: Macromol Biosci. 2011 Jan 10;11(1):36-49
references.pmid: 20967797
references.citation: Stem Cells Dev. 2008 Feb;17(1):29-39
references.pmid: 18271698
references.citation: Biomaterials. 2011 May;32(13):3413-22
references.pmid: 21316755
references.citation: Nat Mater. 2007 Dec;6(12):997-1003
references.pmid: 17891143
references.citation: Nature. 2005 Feb 17;433(7027):760-4
references.pmid: 15716955
references.citation: Integr Biol (Camb). 2009 Jan;1(1):70-9
references.pmid: 20023793
references.citation: Nat Rev Mol Cell Biol. 2009 Jan;10(1):34-43
references.pmid: 19197330
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4872-7
references.pmid: 20194780
references.citation: Nat Nanotechnol. 2011 Jan;6(1):13-22
references.pmid: 21151110
references.citation: Nat Biotechnol. 2007 Feb;25(2):238-43
references.pmid: 17237769
references.citation: Biotechnol Bioeng. 2011 Jul;108(7):1693-703
references.pmid: 21337336
references.citation: Stem Cells. 2010 Mar 31;28(3):564-72
references.pmid: 20082286
references.citation: Biomaterials. 2007 Oct;28(28):4068-77
references.pmid: 17576011
references.citation: J Biomed Mater Res A. 2004 Dec 15;71(4):602-7
references.pmid: 15499636
references.citation: Lab Chip. 2008 Jul;8(7):1056-61
references.pmid: 18584079
references.citation: Biomaterials. 2007 Apr;28(10):1830-7
references.pmid: 17208295
references.citation: Biochem Biophys Res Commun. 2003 Jul 25;307(2):355-61
references.pmid: 12859964
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):1970-5
references.pmid: 10696111
references.citation: Nanotechnology. 2011 May 27;22(21):212001
references.pmid: 21451238
references.citation: Adv Mater. 2009 Sep 4;21(32-33):3255-68
references.pmid: 20882496
references.citation: Stem Cells. 2007 May;25(5):1241-51
references.pmid: 17234993
references.citation: Dev Cell. 2011 Jul 19;21(1):35-47
references.pmid: 21763607
references.citation: Dev Cell. 2011 Jan 18;20(1):9-18
references.pmid: 21238921