Injectable calcium phosphate with hydrogel fibers encapsulating induced pluripotent, dental pulp and bone marrow stem cells for bone repair

Mater Sci Eng C Mater Biol Appl. 2016 Dec 1:69:1125-36. doi: 10.1016/j.msec.2016.08.019. Epub 2016 Aug 10.

Abstract

Human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs), dental pulp stem cells (hDPSCs) and bone marrow MSCs (hBMSCs) are exciting cell sources in regenerative medicine. However, there has been no report comparing hDPSCs, hBMSCs and hiPSC-MSCs for bone engineering in an injectable calcium phosphate cement (CPC) scaffold. The objectives of this study were to: (1) develop a novel injectable CPC containing hydrogel fibers encapsulating stem cells for bone engineering, and (2) compare cell viability, proliferation and osteogenic differentiation of hDPSCs, hiPSC-MSCs from bone marrow (BM-hiPSC-MSCs) and from foreskin (FS-hiPSC-MSCs), and hBMSCs in CPC for the first time. The results showed that the injection did not harm cell viability. The porosity of injectable CPC was 62%. All four types of cells proliferated and differentiated down the osteogenic lineage inside hydrogel fibers in CPC. hDPSCs, BM-hiPSC-MSCs, and hBMSCs exhibited high alkaline phosphatase, runt-related transcription factor, collagen I, and osteocalcin gene expressions. Cell-synthesized minerals increased with time (p<0.05), with no significant difference among hDPSCs, BM-hiPSC-MSCs and hBMSCs (p>0.1). Mineralization by hDPSCs, BM-hiPSC-MSCs, and hBMSCs inside CPC at 14d was 14-fold that at 1d. FS-hiPSC-MSCs were inferior in osteogenic differentiation compared to the other cells. In conclusion, hDPSCs, BM-hiPSC-MSCs and hBMSCs are similarly and highly promising for bone tissue engineering; however, FS-hiPSC-MSCs were relatively inferior in osteogenesis. The novel injectable CPC with cell-encapsulating hydrogel fibers may enhance bone regeneration in dental, craniofacial and orthopedic applications.

Keywords: Bone marrow stem cells; Calcium phosphate cement; Cell-encapsulating fibers; Dental pulp stem cells; Human induced pluripotent stem cells.

MeSH terms

  • Alginates / chemistry
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Bone Regeneration
  • Calcium Phosphates / chemistry*
  • Cell Culture Techniques / instrumentation
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Chitosan / chemistry
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Core Binding Factors / genetics
  • Core Binding Factors / metabolism
  • Dental Pulp / cytology
  • Dental Pulp / metabolism
  • Fibrin / chemistry
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Immunophenotyping
  • Microscopy, Fluorescence
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Porosity
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry

Substances

  • Alginates
  • Calcium Phosphates
  • Collagen Type I
  • Core Binding Factors
  • Hexuronic Acids
  • Osteocalcin
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Glucuronic Acid
  • Fibrin
  • Chitosan
  • calcium phosphate