Publication Date:
2010-07-22
Description:
Stem cells that naturally reside in adult tissues, such as muscle stem cells (MuSCs), exhibit robust regenerative capacity in vivo that is rapidly lost in culture. Using a bioengineered substrate to recapitulate key biophysical and biochemical niche features in conjunction with a highly automated single-cell tracking algorithm, we show that substrate elasticity is a potent regulator of MuSC fate in culture. Unlike MuSCs on rigid plastic dishes (approximately 10(6) kilopascals), MuSCs cultured on soft hydrogel substrates that mimic the elasticity of muscle (12 kilopascals) self-renew in vitro and contribute extensively to muscle regeneration when subsequently transplanted into mice and assayed histologically and quantitatively by noninvasive bioluminescence imaging. Our studies provide novel evidence that by recapitulating physiological tissue rigidity, propagation of adult muscle stem cells is possible, enabling future cell-based therapies for muscle-wasting diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929271/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, P M -- Havenstrite, K L -- Magnusson, K E G -- Sacco, A -- Leonardi, N A -- Kraft, P -- Nguyen, N K -- Thrun, S -- Lutolf, M P -- Blau, H M -- 2 T32 HD007249/HD/NICHD NIH HHS/ -- 52005886/Howard Hughes Medical Institute/ -- AG009521/AG/NIA NIH HHS/ -- AG020961/AG/NIA NIH HHS/ -- CA09151/CA/NCI NIH HHS/ -- HL096113/HL/NHLBI NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG020961/AG/NIA NIH HHS/ -- R01 AG020961-06A2/AG/NIA NIH HHS/ -- R01 AG020961-07/AG/NIA NIH HHS/ -- R01 HL096113/HL/NHLBI NIH HHS/ -- R01 HL096113-03/HL/NHLBI NIH HHS/ -- T32 CA009151/CA/NCI NIH HHS/ -- T32 CA009151-35/CA/NCI NIH HHS/ -- T32 HD007249/HD/NICHD NIH HHS/ -- T32 HD007249-25/HD/NICHD NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- U01 HL100397-01/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1078-81. doi: 10.1126/science.1191035. Epub 2010 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647425" target="_blank"〉PubMed〈/a〉
Keywords:
Algorithms
;
Animals
;
Cell Count
;
Cell Culture Techniques/*methods
;
Cell Death
;
Cell Differentiation
;
Cell Division
;
Cell Lineage
;
Cell Separation
;
Cell Survival
;
Cells, Cultured
;
Elastic Modulus
;
Hydrogels
;
Mice
;
Mice, Inbred C57BL
;
Mice, Inbred NOD
;
Mice, SCID
;
Mice, Transgenic
;
Muscle Fibers, Skeletal/*cytology/physiology
;
Muscle, Skeletal/*cytology
;
Polyethylene Glycols
;
Regeneration
;
Satellite Cells, Skeletal Muscle/cytology
;
Stem Cell Niche/*physiology
;
Stem Cell Transplantation
;
Stem Cells/cytology/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
