Reprogramming in vivo produces teratomas and iPS cells with totipotency features.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model study (bench/in vivo mouse experimentation)
PubMed 24025773 · doi:10.1038/nature12586
What was done
Transitory expression of Oct4, Sox2, Klf4, and c-Myc was induced in reprogrammable mice. Researchers assessed multiple internal organs (stomach, intestine, pancreas, kidney) for teratomas and the pluripotency marker NANOG, evaluated haematopoietic cell reprogramming using bone marrow transplantation, isolated circulating iPS cells from blood for transcriptome analysis, and tested cellular plasticity via trophectoderm contribution and intraperitoneal injection.
What was found
In vivo factor induction generated teratomas across multiple organs and produced NANOG-positive dedifferentiated cell clusters in stomach, intestine, pancreas, and kidney tissues. Bone marrow transplantation confirmed in situ haematopoietic reprogramming. Reprogrammable mice developed circulating iPS cells whose transcriptomes were closer to embryonic stem cells than standard in vitro iPS cells. In vivo iPS cells contributed to the trophectoderm lineage and formed embryo-like structures expressing embryonic and extraembryonic markers. The abstract reports no numerical values.
Why it matters
This study provides proof of concept that full cellular reprogramming to pluripotency can occur directly within living mammalian organs, yielding cells with totipotency-like characteristics. It laid foundational groundwork for exploring in vivo reprogramming and tissue regeneration.
Limits
The abstract provides no sample sizes (n = ?), quantitative yields, or efficiency rates. Induction resulted in widespread teratoma formation, highlighting severe oncogenic risks of uncontrolled reprogramming. Findings are limited to transgenic mouse models and cannot be directly extrapolated to human clinical applications.
Cited by
- supports In vivo expression of all four original Yamanaka factors (OSKM) leads to tissue dysfunction, teratoma/cancer formation, or death in animals.