Departmental Papers (Dental)

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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.


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.


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



Date Posted: 10 February 2023

This document has been peer reviewed.