Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates.
J N HarvestineT Gonzalez-FernandezA SebastianN R HumDamian C GenetosG G LootsJ Kent LeachPublished in: Science advances (2020)
Cell-derived extracellular matrix (ECM) provides a niche to promote osteogenic differentiation, cell adhesion, survival, and trophic factor secretion. To determine whether osteogenic preconditioning would improve the bone-forming potential of unfractionated bone marrow aspirate (BMA), we perfused cells on ECM-coated scaffolds to generate naïve and preconditioned constructs, respectively. The composition of cells selected from BMA was distinct on each scaffold. Naïve constructs exhibited robust proangiogenic potential in vitro, while preconditioned scaffolds contained more mesenchymal stem/stromal cells (MSCs) and endothelial cells (ECs) and exhibited an osteogenic phenotype. Upon implantation into an orthotopic calvarial defect, BMA-derived ECs were present in vessels in preconditioned implants, resulting in robust perfusion and greater vessel density over the first 14 days compared to naïve implants. After 10 weeks, human ECs and differentiated MSCs were detected in de novo tissues derived from naïve and preconditioned scaffolds. These results demonstrate that bioreactor-based preconditioning augments the bone-forming potential of BMA.
Keyphrases
- bone marrow
- mesenchymal stem cells
- endothelial cells
- extracellular matrix
- tissue engineering
- umbilical cord
- induced apoptosis
- cell cycle arrest
- ischemia reperfusion injury
- cell adhesion
- soft tissue
- wastewater treatment
- bone mineral density
- high glucose
- gene expression
- endoplasmic reticulum stress
- stem cells
- human health
- pluripotent stem cells
- contrast enhanced
- climate change
- vascular endothelial growth factor
- cell death
- cell proliferation
- postmenopausal women