PMID- 22622142
OWN - NLM
STAT- MEDLINE
DCOM- 20120924
LR  - 20220321
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 33
IP  - 24
DP  - 2012 Aug
TI  - Reprogramming of human fibroblasts into multipotent cells with a single ECM 
      proteoglycan, fibromodulin.
PG  - 5821-31
LID - 10.1016/j.biomaterials.2012.04.049 [doi]
AB  - Pluripotent and/or multipotent stem cell-based therapeutics are a vital component 
      of tissue engineering and regenerative medicine. The generation or isolation of 
      safer and readily available stem cell sources will significantly aid clinical 
      applications. We report here a technique using a single molecule, recombinant 
      human fibromodulin protein (FMOD), to reprogram human fibroblasts into 
      multipotent cells. Like virally-induced pluripotent stem (iPS) cells, FMOD 
      reprogrammed (FReP) cells express pluripotency markers, form embryoid bodies 
      (EBs), and differentiate into ectoderm, mesoderm, and endoderm derivatives in 
      vitro. Notably, FReP cells regenerate muscle and bone tissues but do not generate 
      teratomas in vivo. Unlike iPS cells, undifferentiated FReP cells proliferate 
      slowly and express low proto-oncogene c-MYC and unexpectedly high levels of 
      cyclin-dependent kinase inhibitors p15(Ink4B) and p21(WAF1/Cip1). Remarkably, in 
      a fashion reminiscent of quiescent stem cells, the slow replicative phenotype of 
      undifferentiated FReP cells reverses after differentiation induction, with 
      differentiating FReP cells proliferating faster and expressing less p15(Ink4B) 
      and p21(WAF1/Cip1) than differentiating iPS cells. Overall, single protein, 
      FMOD-based, cell reprograming bypasses the risks of mutation, gene instability, 
      and malignancy associated with genetically-modified iPS cells, and provides an 
      alternative strategy for engineering patient-specific multipotent cells for basic 
      research and therapeutic application.
CI  - Published by Elsevier Ltd.
FAU - Zheng, Zhong
AU  - Zheng Z
AD  - Dental and Craniofacial Research Institute and Section of Orthodontics, School of 
      Dentistry, University of California, Los Angeles, CA 90095-1759, USA.
FAU - Jian, Jia
AU  - Jian J
FAU - Zhang, Xinli
AU  - Zhang X
FAU - Zara, Janette N
AU  - Zara JN
FAU - Yin, Wei
AU  - Yin W
FAU - Chiang, Michael
AU  - Chiang M
FAU - Liu, Yi
AU  - Liu Y
FAU - Wang, Joyce
AU  - Wang J
FAU - Pang, Shen
AU  - Pang S
FAU - Ting, Kang
AU  - Ting K
FAU - Soo, Chia
AU  - Soo C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120521
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (FMOD protein, human)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proteoglycans)
RN  - 0 (Proto-Oncogene Mas)
RN  - 126468-95-9 (Fibromodulin)
SB  - IM
MH  - Adult
MH  - Bone and Bones/cytology
MH  - Cell Differentiation
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - *Cellular Reprogramming
MH  - Extracellular Matrix Proteins/*metabolism
MH  - Fibroblasts/*cytology/*metabolism
MH  - Fibromodulin
MH  - Gene Expression Profiling
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/metabolism
MH  - Infant, Newborn
MH  - Muscle, Skeletal/cytology
MH  - Proteoglycans/*metabolism
MH  - Proto-Oncogene Mas
EDAT- 2012/05/25 06:00
MHDA- 2012/09/25 06:00
CRDT- 2012/05/25 06:00
PHST- 2012/04/10 00:00 [received]
PHST- 2012/04/21 00:00 [accepted]
PHST- 2012/05/25 06:00 [entrez]
PHST- 2012/05/25 06:00 [pubmed]
PHST- 2012/09/25 06:00 [medline]
AID - S0142-9612(12)00488-7 [pii]
AID - 10.1016/j.biomaterials.2012.04.049 [doi]
PST - ppublish
SO  - Biomaterials. 2012 Aug;33(24):5821-31. doi: 10.1016/j.biomaterials.2012.04.049. 
      Epub 2012 May 21.