title: Elastic properties of induced pluripotent stem cells.
abstract: The recent technique of transducing key transcription factors into unipotent cells (fibroblasts) to generate pluripotent stem cells (induced pluripotent stem cells [iPSCs]) has significantly changed the stem cell field. These cells have great promise for many clinical applications, including that of regenerative medicine. Our findings show that iPSCs can be derived from human adipose-derived stromal cells (hASCs), a notable advancement in the clinical applicability of these cells. To investigate differences between two iPS cell lines (fibroblast-iPSC and hASC-iPSC), and also the gold standard human embryonic stem cell, we looked at cell stiffness as a possible indicator of cell differentiation-potential differences. We used atomic force microscopy as a tool to determine stem cell stiffness, and hence differences in material properties between cells. Human fibroblast and hASC stiffness was also ascertained for comparison. Interestingly, cells exhibited a noticeable difference in stiffness. From least to most stiff, the order of cell stiffness was as follows: hASC-iPSC, human embryonic stem cell, fibroblast-iPSC, fibroblasts, and, lastly, as the stiffest cell, hASC. In comparing hASC-iPSCs to their origin cell, the hASC, the reprogrammed cell is significantly less stiff, indicating that greater differentiation potentials may correlate with a lower cellular modulus. The stiffness differences are not dependent on cell culture density; hence, material differences between cells cannot be attributed solely to cell-cell constraints. The change in mechanical properties of the cells in response to reprogramming offers insight into how the cell interacts with its environment and might lend clues to how to efficiently reprogram cell populations as well as how to maintain their pluripotent state.
authors.affiliation: Rapid Prototyping Laboratory, Department of Mechanical Engineering, School of Engineering, Stanford University, Stanford, California, USA.
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Hammerick
authors.forename: Zubin
authors.initials: Z
authors.lastname: Huang
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Mai T
authors.initials: MT
authors.lastname: Lam
authors.forename: Fritz B
authors.initials: FB
authors.lastname: Prinz
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.forename: George W
authors.initials: GW
authors.lastname: Commons
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D055119:Elastic Modulus / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*
references.citation: Stem Cell Res. 2009 Mar;2(2):113-24
references.pmid: 19383417
references.citation: FASEB J. 2006 May;20(7):811-27
references.pmid: 16675838
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15720-5
references.pmid: 19805220
references.citation: Eur J Cell Biol. 2009 May;88(5):273-83
references.pmid: 19167776
references.citation: J Biomech Eng. 2009 Jun;131(6):061011
references.pmid: 19449965
references.citation: Cell. 2007 Nov 30;131(5):861-72
references.pmid: 18035408
references.citation: Pediatr Surg Int. 2010 Jan;26(1):3-10
references.pmid: 19727766
references.citation: Nat Mater. 2010 Jan;9(1):82-8
references.pmid: 19838182
references.citation: J Biomech. 2008;41(9):2055-9
references.pmid: 18501365
references.citation: Stem Cells. 2009 Sep;27(9):2092-102
references.pmid: 19544411
references.citation: Cell. 2006 Aug 25;126(4):677-89
references.pmid: 16923388
references.citation: J Craniomaxillofac Surg. 2004 Dec;32(6):370-3
references.pmid: 15555520
references.citation: Nat Biotechnol. 2004 May;22(5):560-7
references.pmid: 15077117