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Clonogenic analysis reveals reserve stem cells in postnatal mammals. II. Pluripotent epiblastic-like stem cells. Anat Rec A Discov Mol Cell Evol Biol 2004 Mar;277(1):178-203

Date

02/26/2004

Pubmed ID

14983513

DOI

10.1002/ar.a.20000

Scopus ID

2-s2.0-10744226582 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

Undifferentiated cells have been identified in the prenatal blastocyst, inner cell mass, and gonadal ridges of rodents and primates, including humans. After isolation these cells express molecular and immunological markers for embryonic cells, capabilities for extended self-renewal, and telomerase activity. When allowed to differentiate, embryonic stem cells express phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. When implanted in vivo, undifferentiated noninduced embryonic stem cells formed teratomas. In this report we describe a cell clone isolated from postnatal rat skeletal muscle and derived by repetitive single-cell clonogenic analysis. In the undifferentiated state it consists of very small cells having a high ratio of nucleus to cytoplasm. The clone expresses molecular and immunological markers for embryonic stem cells. It exhibits telomerase activity, which is consistent with its extended capability for self-renewal. When induced to differentiate, it expressed phenotypic markers for tissues of ectodermal, mesodermal, and endodermal origin. The clone was designated as a postnatal pluripotent epiblastic-like stem cell (PPELSC). The undifferentiated clone was transfected with a genomic marker and assayed for alterations in stem cell characteristics. No alterations were noted. The labeled clone, when implanted into heart after injury, incorporated into myocardial tissues undergoing repair. The labeled clone was subjected to directed lineage induction in vitro, resulting in the formation of islet-like structures (ILSs) that secreted insulin in response to a glucose challenge. This study suggests that embryonic-like stem cells are retained within postnatal mammals and have the potential for use in gene therapy and tissue engineering.

Author List

Young HE, Duplaa C, Yost MJ, Henson NL, Floyd JA, Detmer K, Thompson AJ, Powell SW, Gamblin TC, Kizziah K, Holland BJ, Boev A, Van De Water JM, Godbee DC, Jackson S, Rimando M, Edwards CR, Wu E, Cawley C, Edwards PD, Macgregor A, Bozof R, Thompson TM, Petro GJ Jr, Shelton HM, McCampbell BL, Mills JC, Flynt FL, Steele TA, Kearney M, Kirincich-Greathead A, Hardy W, Young PR, Amin AV, Williams RS, Horton MM, McGuinn S, Hawkins KC, Ericson K, Terracio L, Moreau C, Hixson D, Tobin BW, Hudson J, Bowyer FP 3rd, Black AC Jr

Author

Thomas Clark Gamblin MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Colony-Forming Units Assay
Male
Pluripotent Stem Cells
Rats
Rats, Inbred WF
Rats, Sprague-Dawley
Stem Cells