Aging in the mouse and perspectives of rejuvenation through induced pluripotent stem cells (iPSCs).
The mouse is a perfect model to study aging in mammals. It has a relatively short life span and genetic manipulations in this species are well established. Most interestingly, the mouse is a fantastic tool to produce stem cells. Forced expression of only four transcription factors (Oct3/4, Sox2, Klf4, and c-Myc) in murine and human somatic cells resets the expression of genes that are characteristic of differentiated cells and consequently induces the formation of pluripotent stem cells (iPSCs). This technology opens new and exciting possibilities in medical research, especially personalized cell therapies for treating human disease. To treat damaged tissues or repair organs in elderly patients, it will be necessary to establish iPSCs from their tissues. To determine the feasibility of using this technology with elderly patients, we asked whether it was indeed possible to establish iPSCs from the tissues of aged mice and to differentiate them to tissue cells. We succeeded in establishing iPSC clones using bone marrow (BM) from 21-month-old EGFP-C57BL/6 mice, which had been cultured for 4 days in the presence of granulocyte macrophage-colony stimulating factor (GM-CSF). Our iPSCs from aged mice (aged iPSCs) and those from mouse embryonic fibroblasts (MEFs) strongly expressed SSEA-1 and Pou5f1, and showed strong alkaline phosphatase (AP) activity. Our aged iPSCs made teratomas when injected into the back skin of syngeneic mice, and differentiated to tissue cells of three germ lines in vitro. Further experiments to make chimeric mice and germ line cells will determine whether the aged iPSCs possess the properties of much younger cells and are capable of regenerating aged mice.
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. kisobe@med.nagoya-u.ac.jp
Ken-ichi
K
Isobe
Zhao
Z
Cheng
Sachiko
S
Ito
Naomi
N
Nishio
D000375:Aging; D000818:Animals; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008822:Mice, Transgenic; D012060:Rejuvenation; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors