Angiogenic activity mediates bone repair from human pluripotent stem cell-derived osteogenic cells

Abstract

Human pluripotent stem cells provide a standardized resource for bone repair. However, criteria to determine which exogenous cells best heal orthopedic injuries remain poorly defined. We evaluated osteogenic progenitor cells derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). Phenotypic and genotypic analyses demonstrated that these hESCs/hiPSCs are similar in their osteogenic differentiation efficiency and they generate osteogenic cells comparable to osteogenic cells derived from mesenchymal stromal cells (BM-MSCs). However, expression of angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor in these osteogenic progenitor cells are markedly different, suggesting distinct pro-angiogenic potential of these stem cell derivatives. Studies to repair a femur non-union fracture demonstrate only osteogenic progenitor cells with higher pro-angiogenic potential significantly enhance bone repair in vivo. Together, these studies highlight a key role of pro-angiogenic potential of transplanted osteogenic cells for effective cell-mediated bone repair.

iPS cell technologies and their prospect for bone regeneration and disease modeling: A mini review

“…However, these drugs are associated with numerous adverse effects. Thus, iPSCs-based therapy represents a promising new approach for bone repair and regeneration [42] .…”

An improved method to produce clinical scale natural killer cells from human pluripotent stem cells

“…We have successfully produced NK cells from several different iPSC lines, including those derived from human fibroblasts (FiPSC), human peripheral blood mononuclear cells (PBiPSCs) 23 , or human CD34+ cells isolated from umbilical cord blood (UiPSC) 8 . Human ES cell line H9 was obtained from Wicell, Madison WI.…”

Adipose-derived mesenchymal stem/stromal cells: from the lab bench to the basic concepts for clinical translation

“…In order to enhance osseointegration, it is of outstanding relevance to define three features that should have bone grafts: (1) osteogenesis: is the process by which new bone is synthesized, it requires cells with bone differentiation capacity ; (2) osteoinduction: MSC are recruited to differentiate, this recruitment needs the regulation of growth factors and cytokines; (3) osteoconduction: is the three-dimensional growth of capillaries, perivascular tissue and stem cells from the receiving area of the host to the graft, generating a scaffold with the niche characteristics that favors the host-graft interface for regeneration (Zárate-Kalfópulos and Reyes-Sánchez, 2006). Some cases in which MSC per se have been enough to repair bone defects (Lee et al, 2015;Fu et al, 2016;Zou et al, 2016) have been shown, but in general, the gold standard therapeutic strategy is to combine the components to induce bone growth and regeneration, taking into account the three above mentioned characteristics that should have bone grafts (Romagnoli and Brandi, 2014). Most suitable scaffolds must have pores that allow cell infiltration and extracellular matrix deposition; permit incorporation and control drugs, growth factors and bioactive components release; and should be comprised of resorbable materials so that they would be replaced by newly-formed bone over time (Romagnoli and Brandi, 2014).…”