The Effects of Adipose-Derived Stem Cells Differentiated Into Endothelial Cells and Osteoblasts on Healing of Critical Size Calvarial Defects

Abstract

Delayed vascularization and resultant resorption limits the clinical use of tissue engineered bony constructs. The objective of this study is to develop a strategy to accelerate the neovascularization of tissue-engineered bony constructs using endothelial differentiated adipose-derived stem cells (ASC). The authors harvested ASC from inguinal fat pads of male Lewis rats (n = 5) and induced toward endothelial and osteoblastic lineages. The authors created critical size calvarial defects on male Lewis rats (n = 30) and randomized the animals into 4 groups. For the repair of the defects the authors used hydroxyapatite/poly(lactide-co-glycolide) [HA-PLG] scaffolds in group I, HA-PLG scaffolds seeded with ASC in group II, HA-PLG scaffolds seeded with ASC-derived endothelial cells in group III, and HA-PLG scaffolds seeded with ASC-derived osteoblasts in group IV. The authors evaluated the bone healing histologically and with micro-computed tomography (CT) scans 8 weeks later. Adipose-derived stem cells exhibited the characteristics of endothelial and osteogenic lineages, and attached on HA-PLG scaffolds after differentiation. Micro-CT analysis revealed that highest bone mineral density was in group IV (1.46 ± 0.01 g/cm) followed by groups III (1.43 ± 0.05 g/cm), I (1.42 ± 0.05 g/cm), and II (1.3 ± 0.1 g/cm). Hematoxylin-Eosin and Masson Trichrome staining revealed similar results with the highest bone regeneration in group IV followed by groups II, III, and I. Regenerated bone in group IV also had the highest vascular density, but none of these differences achieved statistical significance (P > 0.05). The ASC-derived endothelial cells and osteoblasts provide a limited increase in calvarial bone healing when combined with HA-PLG scaffolds.

The combination of a poly‐caprolactone/nano‐hydroxyapatite honeycomb scaffold and mesenchymal stem cells promotes bone regeneration in rat calvarial defects

“…These cells are known to release cell survival and proliferative factors and to have immunomodulatory properties, thus controlling inflammation and modifying nearby immune cells (Kiernan, Wolvius, Brama, & Farrell, 2018). The positive effect of adding MSCs to a PCL scaffold on bone regeneration has already been demonstrated in, for example, a rabbit knee defect model (with a PCL-TCP scaffold) (Shao, Goh, Hutmacher, Lee, & Zigang, 2006), a rat calvarial defect model (with a PLG-HA scaffold) (Orbay, Busse, Leach, & Sahar, 2017), and a porcine critical-sized bone defect model (with a PCL-TCP/HA scaffold) (Jensen et al, 2016).…”

A novel method to improve the osteogenesis capacity of hUCMSCs with dual‐directional pre‐induction under screened co‐culture conditions

“…Furthermore, the composition of the induction medium is different though we all adopted VEGF as the main component. The including 5, 37 7, 42 9, 34 12, 35 14 days 38,43 or a much longer period of time.…”

Co‐transplantation of Wharton's jelly mesenchymal stem cell‐derived osteoblasts with differentiated endothelial cells does not stimulate blood vessel and osteoid formation in nude mice models

“…Moreover, advances in foetal medicine now allow the prenatal diagnosis of various diseases and malformations (e.g., cleft palate); this creates an opportunity to harvest the patient's own umbilical cord and/or cord blood cells for bone repair. The osteogenic potential of WJMSCs has been confirmed in some in vivo studies (Johari et al, ; Kim SS et al, ; Orbay, Busse, Leach, & Sahar, ).…”