| نویسندگان | Zaniar Ghazizadeh, Hassan Rassouli, Hananeh Fonoudi, Mehdi Alikhani, Mahmood Talkhabi, Amir Darbandi-Azar, Shuibing Chen, Hossein Baharvand, Nasser Aghdami, Ghasem Hosseini Salekdeh |
|---|---|
| نشریه | Molecular biotechnology |
| نوع مقاله | Full Paper |
| تاریخ انتشار | 2017/6/1 |
| رتبه نشریه | ISI |
| نوع نشریه | چاپی |
| کشور محل چاپ | ایالات متحدهٔ امریکا |
چکیده مقاله
Abstract Derivation of cardiomyocytes directly from
patients’ own fibroblasts could offer a new therapeutic
approach for those with ischemic heart disease. An essential
step toward clinical application is to establish safe
conversion of human fibroblasts into a cardiac fate. Here
we aimed to efficiently and safely generate cardiomyocytes
from human fibroblasts by direct delivery of reprogramming
recombinant cell permeant form of reprogramming
proteins followed by cardio-inductive signals. Human fetal
and adult fibroblasts were transiently exposed to transactivator
of transcription-fused recombinant OCT4, SOX2,
KLF4 and c-MYC for 2 weeks and then were directly
differentiated toward protein-induced cardiomyocyte-like
cells (p-iCLCs) in a cardiac fate niche, carried out by
treatment with a set of cardiogenic small molecules
(sequential treatment of Chir, and IWP-2, SB431542 and
purmorphamine). The cells showed cardiac phenotype over
a period of 3 weeks without first undergoing reprogramming
into or through a pluripotent intermediate, shown by
lack of expression of key pluripotency markers. p-iCLCs
exhibited cardiac features at both the gene and protein
levels. Our study provides an alternative method for the
generation of p-iCLCs which shortcut reprogramming
toward allogeneic cardiomyocytes in a safe and efficient
manner and could facilitate generation of genetic materialfree
cardiomyocytes.