Mineral particles modulate osteo-chondrogenic differentiation of embryonic stem cell aggregates

Abstract

Pluripotent stem cell aggregates offer an attractive approach to emulate embryonic morphogenesis and skeletal development. Calcium phosphate (CaP) based biomaterials have been shown to promote bone healing due to their osteoconductive and potential osteoinductive properties. In this study, we hypothesized that incorporation of CaP-coated hydroxyapatite mineral particles (MPs) within murine embryonic stem cell (ESC) aggregates could promote osteo-chondrogenic differentiation. Our results demonstrated that MP alone dose-dependently promoted the gene expression of chondrogenic and early osteogenic markers. In combination with soluble osteoinductive cues, MPs enhanced the hypertrophic and osteogenic phenotype, and mineralization of ESC aggregates. Additionally, MPs dose-dependently reduced ESC pluripotency and thereby decreased the size of teratomas derived from MP-incorporated ESC aggregates in vivo. Our data suggested a novel yet simple means of using mineral particles to control stem cell fate and create an osteochondral niche for skeletal tissue engineering applications.

Segmentally Demineralized Cortical Bone With Stem Cell-Derived Matrix Promotes Proliferation, Migration and Differentiation of Stem Cells in vitro

“…The acceleration in osteogenic and chondrogenic differentiation of BMSCs may be due to the presence of hydroxyapatite and bone morphogenetic protein (BMP), and the presence of hydroxyapatite, BMP-2 and BMP-6 in the bone have been reported to direct osteogenic and chondrogenic differentiation of BMSCs and promote new bone and cartilage formation (Estes et al, 2006;Garrison et al, 2010;Blair et al, 2017;Rogina et al, 2017). Several studies have found a dose-dependent relationship between Ca/ P elements released from scaffolds and osteochondrogenic differentiation of stem cells, and a higher dose of Ca/P promoted osteogenic differentiation but inhibited chondrogenic differentiation (Gigout et al, 2005;Wang et al, 2016). The difference between the results of our study and those of previous studies may be due to the different settings of the control group.…”

Bone regeneration in critically sized rat mandible defects through the endochondral pathway using hydroxyapatite-coated 3D-printed Ti6Al4V scaffolds

“…One study by Isao Shibuya showed that the CaP-coated hydroxyapatite mineral particles (MPs) promoted the gene expression of chondrogenic and early osteogenic markers. 50 However, another study showed that octacalcium phosphate suppresses chondrogenic differentiation of ATDC5 cells. 51 In order to mimic the endochondral ossification process, we firstly produced a cartilage temple by seeding the BMSCs onto the scaffolds for chondrogenic priming in vitro .…”

Bone defect reconstruction via endochondral ossification: A developmental engineering strategy

“…121 In another study, CaP-coated HAp mineral particles have been shown to promote the gene expression of chondrogenic markers and enhance the hypertrophic phenotype of ESC aggregates in vitro in a dose-dependent manner. 67 β-TCP has been shown to promote cartilage regeneration and biomineralization 122 and support endochondral bone formation 123 because of its biodegradability, biocompatibility, and bioactivity. β-TCP is often combined with other materials to enhance the chondrogenic and endochondral potential of scaffolds.…”

“…To produce functional bone tissue without these risks, MSCs derived from ESCs (ESC-MSCs), which possess the lineage-specific differentiation potential of MSCs but enhanced proliferative and immunosuppressive capabilities, 64 have also shown the capacity to recapitulate the ECO process and repair bone defects semiautonomously without preimplantation differentiation into osteo- or chondroprogenitors. 65 – 67 Furthermore, embryonic limb-derived progenitor cells can also form bone via the ECO pathway in an ectopic environment, which has been harnessed to bridge parietal bone defects in a mouse model. 68 …”

“… 121 In another study, CaP-coated HAp mineral particles have been shown to promote the gene expression of chondrogenic markers and enhance the hypertrophic phenotype of ESC aggregates in vitro in a dose-dependent manner. 67 …”