Blood Vessel Wall–Derived Endothelial Colony-Forming Cells Enhance Fracture Repair and Bone Regeneration

Abstract

Endochondral bone formation requires new blood vessel formation, and endothelial progenitor cells (EPCs) may play a role in this process. Endothelial colony-forming cells (ECFCs), one subtype of EPCs, isolated from the microvasculature of rat lungs, exhibited cell surface antigen markers and gene products characteristic of endothelial cells and displayed high proliferative potential and an ability to form vessel-like network structures in vitro. The aim of this study was to evaluate whether ECFCs facilitate bone healing during fracture repair and stimulate bone regeneration. When type I collagen sponge containing ECFCs were surgically wrapped around the fractured femurs of rats, newly formed bone mineral at the site of fracture was 13% greater (P = 0.01) and energy to failure was 46% greater (P = 0.01) compared to sponge-wrapped fractures without ECFCs. When ECFCs in type I collagen sponge were surgically implanted into the bone defective area, more new vessels formed locally in comparison with sponge-alone controls and new bone tissues were seen. Further, co-implantation of ECFCs and hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds at the bone defective sites stimulated more new bone tissues than HA/TCP scaffold alone. These results show that cell therapy with vessel wall-derived ECFCs can induce new vessel formation, stimulate new bone formation, and facilitate bone repair and could be a useful approach to treat non-union fractures and bone defects.

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

“…However, in the future, these HAP-GEL constructs may require loading of endothelial progenitor cells to generate microvascularization and promote a faster regeneration. 9 In conclusion, the fabrication of a rigid macroporous TiO 2 -enriched HAP-GEL scaffold was found feasible for bone regeneration applications in calvaria defects. After 12 weeks postimplantation, TiO 2 -HAP-GEL scaffolds loaded with ODMAPCs promoted osteointegration, NFB in the macroporous areas and significantly enhanced bone regeneration.…”

“…This poor collagen-related effect has been recently reported at CSD in rat fibulas. 9 In this latter report, researchers found that cellfree collagen sponges have a very limited microvascular network in both fracture healing and CSD models, unlike HAP-based constructs. 9 Results found here with the implanted cell-free TiO 2 -HAP-GEL were further confirmed within the undecalcified sections with NFB-specific staining and after evaluating the MAR.…”

“…9 In this latter report, researchers found that cellfree collagen sponges have a very limited microvascular network in both fracture healing and CSD models, unlike HAP-based constructs. 9 Results found here with the implanted cell-free TiO 2 -HAP-GEL were further confirmed within the undecalcified sections with NFB-specific staining and after evaluating the MAR. The HAP-GEL without TiO 2 additives had significantly less MAR, osteointegration, and NFB in the porous areas than the HAP-GEL enriched with TiO 2 .…”

“…6,7 The loading of cells on alloplastic grafts such as porous calciumbased scaffolds in the hydroxyapatite form (HAP), followed by in vivo implantation in large bone defects, had been previously shown to promote healing. 8,9 Moreover, injectable and formable calcium-based composites with natural polymeric phases (e.g., gelatin) can further increase their clinical applicability. 10 Titania additives may constitute an advantage by increasing surface hydrophobicity and protein adsorption to further enhance cell adhesion, osteogenic induction, and formability in bone biomaterials, including in HAP-GEL.…”

Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration

“…Regardless of where the circulating EPCs originated, frequency of EPCs in PB or BM is known to be extremely low [6,8,17,[20][21][22][23]. Other studies using rat lung tissues or human renal arteries have shown success in isolating functional ECFCs, but it will be difficult to translate the same approaches to clinical settings [24,25].…”