PMID- 22197570 OWN - NLM STAT- MEDLINE DCOM- 20120508 LR - 20220317 IS - 1878-5905 (Electronic) IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 33 IP - 8 DP - 2012 Mar TI - Mechanical derivation of functional myotubes from adipose-derived stem cells. PG - 2482-91 LID - 10.1016/j.biomaterials.2011.12.004 [doi] AB - Though reduced serum or myoblast co-culture alone can differentiate adipose-derived stem cells (ASCs) into mesenchymal lineages, efficiency is usually not sufficient to restore function in vivo. Often when injected into fibrotic muscle, their differentiation may be misdirected by the now stiffened tissue. Here ASCs are shown to not just simply reflect the qualitative stiffness sensitivity of bone marrow-derived stem cells (BMSCs) but to exceed BMSC myogenic capacity, expressing the appropriate temporal sequence of muscle transcriptional regulators on muscle-mimicking extracellular matrix in a tension and focal adhesion-dependent manner. ASCs formed multi-nucleated myotubes with a continuous cytoskeleton that was not due to misdirected cell division; microtubule depolymerization severed myotubes, but after washout, ASCs refused at a rate similar to pre-treated values. BMSCs never underwent stiffness-mediated fusion. ASC-derived myotubes, when replated onto non-permissive stiff matrix, maintained their fused state. Together these data imply enhanced mechanosensitivity for ASCs, making them a better therapeutic cell source for fibrotic muscle. CI - Copyright (c) 2011 Elsevier Ltd. All rights reserved. FAU - Choi, Yu Suk AU - Choi YS AD - Department of Bioengineering, University of California, San Diego, CA, USA. FAU - Vincent, Ludovic G AU - Vincent LG FAU - Lee, Andrew R AU - Lee AR FAU - Dobke, Marek K AU - Dobke MK FAU - Engler, Adam J AU - Engler AJ LA - eng GR - DP2 OD006460/OD/NIH HHS/United States GR - DP2 OD006460-01/OD/NIH HHS/United States GR - 1DP02 OD006460/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20111223 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (RNA, Messenger) SB - IM MH - Adipose Tissue/*cytology MH - Adult MH - Biomechanical Phenomena MH - Bone Marrow Cells/cytology/metabolism MH - Cell Fusion MH - Cell Lineage MH - Elasticity MH - Extracellular Matrix/metabolism MH - Focal Adhesions/metabolism MH - Gene Expression Regulation MH - Giant Cells/cytology/metabolism MH - Humans MH - Mechanotransduction, Cellular MH - Muscle Development MH - Muscle Fibers, Skeletal/*cytology/metabolism MH - RNA, Messenger/genetics/metabolism MH - Stem Cells/*cytology/metabolism PMC - PMC3261363 MID - NIHMS343520 COIS- Disclosure The authors indicate no potential conflicts of interest. EDAT- 2011/12/27 06:00 MHDA- 2012/05/09 06:00 PMCR- 2013/03/01 CRDT- 2011/12/27 06:00 PHST- 2011/11/23 00:00 [received] PHST- 2011/12/02 00:00 [accepted] PHST- 2011/12/27 06:00 [entrez] PHST- 2011/12/27 06:00 [pubmed] PHST- 2012/05/09 06:00 [medline] PHST- 2013/03/01 00:00 [pmc-release] AID - S0142-9612(11)01459-1 [pii] AID - 10.1016/j.biomaterials.2011.12.004 [doi] PST - ppublish SO - Biomaterials. 2012 Mar;33(8):2482-91. doi: 10.1016/j.biomaterials.2011.12.004. Epub 2011 Dec 23.