Transplanted Endothelial Cells Enhance Orthotopic Bone Regeneration

Abstract

The aim of this study was to determine if endothelial cells could enhance bone marrow stromal-cell-mediated bone regeneration in an osseous defect. Using poly-lactide-co-glycolide scaffolds as cell carriers, we transplanted bone marrow stromal cells alone or with endothelial cells into 8.5-mm calvarial defects created in nude rats. Histological analyses of blood vessel and bone formation were performed, and microcomputed tomography (muCT) was used to assess mineralized bone matrix. Though the magnitude of the angiogenic response between groups was the same, muCT analysis revealed earlier mineralization of bone in the co-transplantation condition. Ultimately, there was a significant increase (40%) in bone formation in the co-transplantation group (33 +/- 2%), compared with the transplantation of bone marrow stromal cells alone (23 +/- 3%). Analysis of these data demonstrates that, in an orthotopic site, transplanted endothelial cells can influence the bone-regenerative capacity of bone marrow stromal cells.

CXCL12/Stromal-Cell-Derived Factor-1 Effectively Replaces Endothelial Progenitor Cells to Induce Vascularized Ectopic Bone

“…When implanted in vivo, ectopic implantations show that combined constructs contain higher density of vasculature than the seeding of MSCs alone [9,12,14] and that bone formation is positively affected by the addition of ECs or EPCs [8][9][10]. At orthotopic locations, some studies claim that there is no beneficial effect on total vessel formation after implantation [6,15], while other results show significantly higher early vascularization using EPCs in combination with MSCs [5,6]. In addition, the stimulating effect on bone formation using combinations of MSCs and ECs or EPCs varies between studies [5,6,15].…”

“…At orthotopic locations, some studies claim that there is no beneficial effect on total vessel formation after implantation [6,15], while other results show significantly higher early vascularization using EPCs in combination with MSCs [5,6]. In addition, the stimulating effect on bone formation using combinations of MSCs and ECs or EPCs varies between studies [5,6,15].…”

Human Adipose Tissue-Derived SSEA-4 Subpopulation Multi-Differentiation Potential Towards the Endothelial and Osteogenic Lineages

“…13 Previous in vivo studies showed that vascularization within engineered constructs using mature endothelial cells (ECs) improved blood perfusion, cell viability, and their survival after implantation. [14][15][16] However, the limited availability and proliferation capability of mature ECs hinder their use in tissue engineering (TE) approaches. 17 Therefore, it became a priority to find a suitable source of ECs that do not present such constrains and that will be ready-to-use for therapeutic applications.…”

Angiogenic and Osteogenic Potential of Bone Repair Cells for Craniofacial Regeneration

“…As a result, some strategies used to engineer and regenerate bone tissue employ cotransplantation of osteoprogenitor cells with either hematopoietic or endothelial cells to help establish a supportive blood supply to the transplanted cells. [16][17][18][19] Although these approaches all hold great promise, it would be more desirable to transplant a cell population that contains cells capable of establishing both a blood supply and regenerating bone.…”