Differential analysis of peripheral blood‐ and bone marrow‐derived endothelial progenitor cells for enhanced vascularization in bone tissue engineering

Abstract

For tissue engineering applications, effective bone regeneration requires rapid neo-vascularization of implanted grafts to ensure the survival of cells in the early post-implantation phase. Incorporation of autologous endothelial progenitor cells (EPCs) for the promotion of primitive vascular network formation ex vivo has offered great promise for improved graft survival, enhanced rate of vascularization and bone regeneration in vivo. For clinical usage, identification of an optimal EPC isolation source from the patient is critical. We have, for the first time, characterized and directly compared EPCs from rabbit peripheral blood and bone marrow (PB-EPCs and BM-EPCs, respectively). PB-EPCs outperformed BM-EPCs on all measures. PB-EPCs displayed typical endothelial cell markers, such as CD31, as well as high angiogenic potential in three-dimensional extracellular matrix in vitro. Furthermore, PB-EPCs cultured simultaneously with mesenchymal stem cells, displayed significantly enhanced expression levels of key osteogenic and vascular markers, including alkaline phosphatase, bone morphogenetic protein 2, and vascular endothelial growth factor. On the contrary, putative BM-EPCs did not express CD31, and instead, expressed key smooth muscle markers. BM-EPCs further failed to display vasculogenic activity. Hence, the highly angiogenic PB-derived EPCs may serve as an ideal cell population for enhanced vascularization and success of engineered bone tissue. ß

Fibroblast-Endothelial Partners for Vascularization Strategies in Tissue Engineering

“…7,9 Although CD34 is characteristically expressed by vascular ECs, 31 some authors have also reported a low signal for CD34 both in HUVECs and OECs, 32 which is in accordance to the fact that CD34 + ECs are enriched for biological functions related to angiogenesis and migration, whereas CD34 -cells are enriched for functions related to proliferation. 33 In addition, these cells displayed the ability for organizing into typical polygonal capillary-like structures at least for 48 h, according to what has been previously described.…”

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

“…43,44 Such vascularization and vascular structure formation has been observed in vitro and in vivo, lending insight into the mechanisms underlying this process. [44][45][46][47] MSCs interact with EPCs both directly through gap junctions and indirectly through paracrine signaling, with major pathways highlighted in Figure 1. 47 Direct contact between MSCs and EPCs may lead to induced endothelial phenotypes, without the addition of exogenous growth factors, in both cell types.…”

The Osteogenic Potential of Human Nondifferentiated and Pre-differentiated Mesenchymal Stem Cells Combined with an Osteoconductive Scaffold – Early Stage Healing

“…It seems to be logical to combine MSCs together with osteoinductive scaffolds to accelerate bone healing. However, vascularization is still an issue that must be addressed (2). Even though stem cells are generally more resistant to hypoxia and low nutrition supply than somatic cells, we must ensure that the growth of the blood vessels is complete before maturation occurs.…”