Age dependence of the human skeletal muscle stem cell in forming muscle tissue.
Human skeletal muscle stem cells from healthy donors aged 2-82 years (n = 13) and from three children suffering from Duchenne Muscular Dystrophy (DMD) were implanted into soleus muscles of immunoincompetent mice and were also expanded in vitro until senescence. Growth of implanted cells was quantified by structural features and by the amount of human DNA present in a muscle. Proliferative capacity in vitro and in vivo was inversely related to age of the donor. In vitro, a decline of about two mean population doublings (MPDs) per 10 years of donor's age was observed. Muscle stem cells from DMD children were prematurely aged. In general, cell preparations with low or decreasing content in desmin-positive cells produced more MPDs than age-matched high-desmin preparations and upon implantation more human DNA and more nonmyogenic than myogenic tissue. Thus, a "Desmin Factor" was derived which predicts "quality" of the human muscle tissue growing in vivo. This factor may serve as a prognostic tool.
Schäfer
Ralf
R
Department of Physiology, University of Bonn, Bonn, Germany.
Knauf
Ulrich
U
Zweyer
Margit
M
Högemeier
Oliver
O
de Guarrini
Francesca
F
Liu
Xia
X
Eichhorn
Heinz Jürgen
HJ
Koch
Franz Walter
FW
Mundegar
Rustam R
RR
Erzen
Ida
I
Wernig
Anton
A
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001706:Biopsy; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000302:isolation & purification; D003893:Desmin / Q000032:analysis; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D033581:Stem Cell Transplantation
D003893:Desmin; D004247:DNA