Fibromodulin Reprogrammed Cells: A Novel Cell Source for Bone Regeneration

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Penn collection
Departmental Papers (Dental)
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Differentiation
Fibromodulin (FMOD)
Fibromodulin reprogrammed (FReP) cells
Osteogenesis
Reprogramming
Animals
Bone Regeneration
Cell Differentiation
Cell Transplantation
Cells
Cultured
Cellular Reprogramming
CHO Cells
Cricetinae
Cricetulus
Culture Media
Extracellular Matrix Proteins
Fibromodulin
Gene Expression Regulation
Humans
Immunohistochemistry
Male
Mice
SCID
Minerals
Osteogenesis
Pluripotent Stem Cells
Proteoglycans
Skull
Bone
Cells
Defects
Differentiation (calculus)
Gene therapy
Genes
Polymethyl methacrylates
Stem cells
fibromodulin
culture medium
fibromodulin
mineral
proteoglycan
scleroprotein
Critical sized defects
Fibromodulin (FMOD)
Fibromodulin reprogrammed cells
Immunohistochemical staining
Osteogenesis
Osteogenic differentiation
Platform technology
Reprogramming
animal experiment
animal model
animal tissue
Article
bone defect
bone development
bone regeneration
calvaria
cell differentiation
controlled study
gene expression profiling
histology
human
human cell
immunohistochemistry
in vivo study
mouse
multipotent stem cell
nonhuman
nuclear reprogramming
priority journal
SCID mouse
stem cell transplantation
animal
bone regeneration
cell culture
cell transplantation
CHO cell line
Cricetulus
culture medium
diagnostic imaging
drug effects
gene expression regulation
genetics
hamster
male
metabolism
nuclear reprogramming
pathology
pharmacology
pluripotent stem cell
skull
Cytology
Dental Materials
Dentistry
Endodontics and Endodontology
Oral and Maxillofacial Surgery
Oral Biology and Oral Pathology
Orthodontics and Orthodontology
Periodontics and Periodontology
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Li, Chen-Shuang
Yang, Pu
Ting, Kang
Aghaloo, Tara
Lee, Soonchul
Zhang, Yulong
Khalilinejad, Kambiz
Murphy, Maxwell C.
Pan, Hsin Chuan
Zhang, Xinli
Contributor
Abstract

Pluripotent or multipotent cell-based therapeutics are vital for skeletal reconstruction in non-healing critical-sized defects since the local endogenous progenitor cells are not often adequate to restore tissue continuity or function. However, currently available cell-based regenerative strategies are hindered by numerous obstacles including inadequate cell availability, painful and invasive cell-harvesting procedures, and tumorigenesis. Previously, we established a novel platform technology for inducing a quiescent stem cell-like stage using only a single extracellular proteoglycan, fibromodulin (FMOD), circumventing gene transduction. In this study, we further purified and significantly increased the reprogramming rate of the yield multipotent FMOD reprogrammed (FReP) cells. We also exposed the 'molecular blueprint' of FReP cell osteogenic differentiation by gene profiling. Radiographic analysis showed that implantation of FReP cells into a critical-sized SCID mouse calvarial defect, contributed to the robust osteogenic capability of FReP cells in a challenging clinically relevant traumatic scenario in vivo. The persistence, engraftment, and osteogenesis of transplanted FReP cells without tumorigenesis in vivo were confirmed by histological and immunohistochemical staining. Taken together, we have provided an extended potency, safety, and molecular profile of FReP cell-based bone regeneration. Therefore, FReP cells present a high potential for cellular and gene therapy products for bone regeneration. © 2016 Elsevier Ltd.

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2016-03-01
Journal title
Biomaterials
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At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California and the Peking University, School and Hospital of Stomatology. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
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