Concise Review: In Vitro Formation of Bone-Like Nodules Sheds Light on the Application of Stem Cells for Bone Regeneration

Abstract

Harnessing the differentiation of stem cells into bone-forming cells represents an intriguing avenue for the creation of functional skeletal tissues. Therefore, a profound understanding of bone development and morphogenesis sheds light on the regenerative application of stem cells in orthopedics and dentistry. In this concise review, we summarize the studies deciphering the mechanisms that govern osteoblast differentiation in the context of in vitro formation of bone-like nodules, including morphologic and molecular events as well as cellular contributions to mineral nucleation, occurring during osteogenic differentiation of stem cells. This article also highlights the limitations of current translational applications of stem cells and opportunities to use the bone-like nodule model for bone regenerative therapies. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1587-1593 SIGNIFICANCEHarnessing the differentiation of stem cells into bone-forming cells represents an intriguing avenue for the creation of functional skeletal tissues. Therefore, a profound understanding of bone development and morphogenesis sheds light on the regenerative application of stem cells in orthopedics and dentistry. In this concise review, studies deciphering the mechanisms that govern osteoblast commitment and differentiation are summarized. This article highlights the limitations of current translational applications of stem cells and the opportunities to use the bone-like nodule model for bone regenerative therapies.

Harnessing Wharton’s jelly stem cell differentiation into bone-like nodule on calcium phosphate substrate without osteoinductive factors

“…In the literature, the initial cell density of bone-like nodules varies from 5 to 35 cells per nodule and its size and thickness increase during the course of differentiation. 20-day-old nodules comprise approximately 100 cells per nodule, with a thickness of 70-100 lm [43]. We next investigated the expression of genes expected to be regulated during osteogenic commitment.…”

<p>Magnesium-doped Nanostructured Titanium Surface Modulates Macrophage-mediated Inflammatory Response for Ameliorative Osseointegration</p>

“… 11 In previous studies, cells in the osteoblastic lineage are often applied as the only choices to assess the effect of osteogenesis in cell experiments when developing novel implant biomaterials. 12 Since immune cells play such an essential part in the regeneration of bone tissues, a novel evaluation system involving both immune cells and bone cells is required to be constructed aiming to develop optimal implant biomaterials.…”

Bioinspired Nanofeatured Substrates: Suitable Environment for Bone Regeneration

“…characterizing osteoblasts). 25 After five days of culture, WJ-SCs on both coatings showed striking changes in cell morphology along with polygonal shape compared to the fibroblastic shape observed on coverslips (Figures 4A1−C1). A cascade of events is established during osteoblast differentiation, including expression of α2/β1 integrin at the membrane, recruitment of vinculin at the focal adhesion complexes with the reorganization of cytoskeleton, nuclear changes, and expression of bone specific markers such as Runx-2, osteopontin (OPN), and osteocalcin (OCN), 26 and are thus described in the following.…”