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.
Department of Physiology, University of Bonn, Bonn, Germany.
Ralf
R
Schäfer
Ulrich
U
Knauf
Margit
M
Zweyer
Oliver
O
Högemeier
Francesca
F
de Guarrini
Xia
X
Liu
Heinz Jürgen
HJ
Eichhorn
Franz Walter
FW
Koch
Rustam R
RR
Mundegar
Ida
I
Erzen
Anton
A
Wernig
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