Bone tissue engineering using adipose‐derived stem cells and endothelial cells: Effects of the cell ratio

Abstract

The reconstruction of critical sized bone defects can be challenging in clinical practice. Critical bone defects can be caused by malformation, cancer, trauma or infection. Regardless of the entity, the current gold standard is autologous tissue transfer, which can be associated with significant donor side morbidity and limited tissue availability. One way to circumvent these problems is the generation of bioartificial bone tissue.For bone formation and regeneration, a sufficient vascularization providing oxygen and nutrition supply is indispensable. [1][2][3] Strategies to improve vascularization in bone tissue engineering applications include the use of angiogenic growth factors, endothelial cells (ECs) and the surgical induced angiogenesis by means of arteriovenous

Is There a Governing Role of Osteocytes in Bone Tissue Regeneration?

“…The unresolved clinical challenges of bone tissue regeneration are related to the limited healing capacity of bone tissue, since current bone tissue regeneration cannot cover all types of bone defects, especially when the bone defect is large and complex. Bone tissue regeneration can be improved if we better understand the exact mechanism that bioactive molecules have on cells involved in bone tissue regeneration [ 61 ]. Moreover, detailed knowledge of the microenvironment at the defect site and how this affects and interacts with cells in the engineered bone is needed.…”

The Adipose-Derived Stem Cell and Endothelial Cell Coculture System—Role of Growth Factors?

“…In this regard, heterotypic cell contacts between endothelial cells and osteoprogenitor cells seem to be the driving force [19]. In a recent work we demonstrated that coculturing adipose derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs) stimulates proliferation, proangiogenic effects and osteogenic differentiation [13]. We translated our in vitro results into the rat arteriovenous loop (AV loop) model.…”

“…Moreover, the application of VEGFA165 reduced the cell number of HUVECs under monoculture conditions compared to the control group. Based on the findings from a previous study, it is alluring to speculate that VEGFA165 concentrations higher than 200 pg/mL might have adverse effects on HUVEC proliferation [13]. From the pertinent literature, it is well-known that VEGF can stimulate the proliferation rate of ADSCs in a dose dependent manner [26].…”

“…Osteogenic differentiation of ADSCs was induced prior to the experiments. For this purpose, ADSCs were cultured in ECGM medium containing an additional 1 × 10 −8 M dexamethasone, 50 µg/mL L-ascorbic acid, 10 mM glycerophosphate and 0.01 µM 1,25-dihydroxyvitamine D3 (all supplements purchased from Sigma, Steinheim, Germany) for 14 days [6,13]. For the following experiments, three experimental groups were performed.…”

“…Moreover, endothelial cells stimulate the osteogenic differentiation of osteoprogenitor cells as indicated by increased matrix mineralization and the production of osteogenic markers. Alkaline phosphatase (ALP) is a prominent early osteogenic marker, which is upregulated in osteoprogenitor cells upon 48-72 h of cocultivation with endothelial cells [12,13]. In a previous study we have been able to prove that coculturing ADSCs and human umbilical vein endothelial cells (HUVECs) in a ratio of 1:1 displays the best effects with regard to proliferation, cell survival and osteogenic differentiation.…”