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

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 14 d was 14-fold that at 1 d. 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.

Injectable calcium phosphate scaffold with iron oxide nanoparticles to enhance osteogenesis via dental pulp stem cells

“…This was performed with proper consent and without patient identification, and was approved by the Institutional Review Board of the University of Maryland at Baltimore (HP-00040437). Cells were isolated as described previously [40]. Briefly, the pulp tissues were minced and digested in a solution of 3 mg/mL of collagenase type I and 4 mg/mL dispase for 30-60 min at 37 C. Cell suspension was obtained by passing the digested tissue through a 70 lm cell strainer.…”

Induced pluripotent stem cells (iPSCs) as a new source of bone in reconstructive surgery: A systematic review and meta-analysis of preclinical studies

“…Bone marrow mesenchymal stem cells are the gold standard cell source for stem cell therapy to replace defective tissue being successfully applied clinically. However, autogenous bone marrow mesenchymal stem cells require an invasive procedure to harvest with limited cell numbers and potency due to aging and keeping their differentiated state (Raisin, Belamie, & Morille, ; Wang, et al, ). Recently, alternative stem cell sources had been discovered as pluripotent stem cells (PSCs) that proved their efficiency to differentiate into several tissue origins (Raisin et al, ; Yamanaka, ).…”

“…iPSCs represent a major breakthrough providing a promising strategy to obtain patient‐specific stem cells for tissue engineering (Wang et al, ) that raised as an alternative to ESCs because the derivation of the PSCs from the early embryos had both ethical and immune system‐related limitations for research and clinical applications despite that ESCs have unlimited high proliferation and replication potential without telomere shortening, karyotype changes, or cells undergoing senescence (H. Liu et al, ).…”

Induced Pluripotent Stem Cells in Dental and Nondental Tissue Regeneration: A Review of an Unexploited Potential

“…Human iPSCs-MSCs seeded on microporous CPC scaffolds using polyethylene glycol (PEG) particles showed upregulation of RUNX2, COL1A1, ALP, OPN, and platelet-derived growth factor receptor-beta (PDGF-R-β) [76]. Similarly, human iPSCs-MSCs seeded on CPC [62,[77][78][79] or poly lactic-co-glycolic acid/poly L-lactic acid (PLGA/PLLA) scaffold combined with macrophages [80] or fast degradable alginate microbeads [69] showed high expression of osteoblast-related genes. Moreover, murine iPSC-derived MSCs seeded onto three-dimensional gelatin scaffold revealed upregulation of several osteoblast-related genes in vitro and in vivo, following subcutaneous implantation in rats [81].…”