title: Fibromodulin reprogrammed cells: A novel cell source for bone regeneration.
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.
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.
authors.forename: Chen-Shuang
authors.initials: CS
authors.lastname: Li
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Pu
authors.initials: P
authors.lastname: Yang
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Aghaloo
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, Gyeonggi-do, 463-712, South Korea.
authors.forename: Soonchul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Khalilinejad
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Maxwell C
authors.initials: MC
authors.lastname: Murphy
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Hsin Chuan
authors.initials: HC
authors.lastname: Pan
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, PR China.
authors.forename: Yan-Heng
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Dental and Craniofacial Research Institute and Division of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA. Electronic address: zzheng@dentistry.ucla.edu.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: UCLA Division of Plastic Surgery and Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA. Electronic address: bsoo@ucla.edu.
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D017690:Cell Transplantation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D000071235:Fibromodulin; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016513:Mice, SCID; D008903:Minerals / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology*; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology
chemical_list: D003470:Culture Media; D016326:Extracellular Matrix Proteins; D008903:Minerals; D011509:Proteoglycans; D000071235:Fibromodulin
keywords: Differentiation; Fibromodulin (FMOD); Fibromodulin reprogrammed (FReP) cells; Osteogenesis; Reprogramming