title: Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium.
abstract: Human induced pluripotent stem cells (hiPSCs) are an exciting cell source with great potential for tissue engineering. Human bone marrow mesenchymal stem cells (hBMSCs) have been used in clinics but are limited by several disadvantages, hence alternative sources of MSCs such as umbilical cord MSCs (hUCMSCs) are being investigated. However, there has been no report comparing hiPSCs, hUCMSCs and hBMSCs for bone regeneration. The objectives of this pilot study were to investigate hiPSCs, hUCMSCs and hBMSCs for bone tissue engineering, and compare their bone regeneration via seeding on biofunctionalized macroporous calcium phosphate cement (CPC) in rat cranial defects. For all three types of cells, approximately 90% of the cells remained alive on CPC scaffolds. Osteogenic genes were up-regulated, and mineral synthesis by cells increased with time in vitro for all three types of cells. The new bone area fractions at 12weeks (mean±sd; n=6) were (30.4±5.8)%, (27.4±9.7)% and (22.6±4.7)% in hiPSC-MSC-CPC, hUCMSC-CPC and hBMSC-CPC respectively, compared to (11.0±6.3)% for control (p<0.05). No significant differences were detected among the three types of stem cells (p>0.1). New blood vessel density was higher in cell-seeded groups than control (p<0.05). De novo bone formation and participation by implanted cells was confirmed via immunohistochemical staining. In conclusion, (1) hiPSCs, hUCMSCs and hBMSCs greatly enhanced bone regeneration, more than doubling the new bone amount of cell-free CPC control; (2) hiPSC-MSCs and hUCMSCs represented viable alternatives to hBMSCs; (3) biofunctionalized macroporous CPC-stem cell constructs had a robust capacity for bone regeneration.
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA; Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. Electronic address: lzhaonf@126.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weir
authors.affiliation: Dr. Anthony Volpe Research Center, American Dental Association Foundation, Gaithersburg, MD 20899, USA.
authors.forename: Jirun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Wenchuan
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Man
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA; Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Mechanical Engineering Department, University of Maryland Baltimore County, Baltimore, MD 21250, USA. Electronic address: hxu@umaryland.edu.
authors.forename: Hockin H K
authors.initials: HH
authors.lastname: Xu
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D002130:Calcium Phosphates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects; D011923:Rats, Nude; D012886:Skull / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D014470:Umbilical Cord / Q000166:cytology*; D055114:X-Ray Microtomography
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; C020243:calcium phosphate
keywords: Bone marrow stem cells; Bone regeneration; Calcium phosphate scaffold; Induced pluripotent stem cells; Umbilical cord stem cells