Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

Abstract

As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bone, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain and osteonecrosis of the jaw.The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence and lower their osteogenic differentiation potential.Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems.This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability and osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs.

Time-Dependent Reduction of Calcium Oscillations in Adipose-Derived Stem Cells Differentiating towards Adipogenic and Osteogenic Lineage

“…This latter observation may be due to the effect of time reducing Ca 2+ dynamics in untreated ASCs, but not in ASCs undergoing osteogenic differentiation. This is interesting because the manipulation of Ca 2+ signalling has been proposed as a pivotal mechanism for the induction of osteogenic differentiation [20,34,35], leading to the development of electrical stimulation-based systems to promote osteogenic differentiation, as a possible tool for bone regeneration [26,27]. As we have shown that spontaneous Ca 2+ oscillations in untreated ASCs are reduced over time, it is plausible to speculate that external stimuli promoting sustained Ca 2+ oscillations may be responsible for osteogenic differentiation.…”

“…After 72 h, standard medium was replaced by StemPro ® adipocyte differentiation basal medium supplemented with StemPro ® adipogenesis supplement (Life Technologies, Thermo Fisher Scientific). After 21 days, differentiation was assessed by Oil RedO staining as described earlier [27].…”

Comparative Transcriptome Analysis of Human Adipose-Derived Stem Cells Undergoing Osteogenesis in 2D and 3D Culture Conditions

“…They are also known as early markers of osteoblast differentiation [ 10 ]. IBPS is known to be expressed in bone, dentin, cementum and calcified cartilage [ 28 , 40 ]. Therefore, we selected those five genes to evaluate osteogenic differentiation by measuring the gene expression levels.…”

Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis

“…On this regard, Yang and colleagues developed a 3D culture system in which osteoblasts collected from the long bone of mouse model of Apert syndrome were homogeneously encapsulated in a poly(ethylene glycol)-diacrylate (PEGDA) 3D hydrogel [194]. Various works in literature demonstrated the importance of physical three-dimensionality of the matrix in regulating osteoblast behaviour, including cell osteogenesis and bone matrix formation (see [195] for an up-to-date review). Indeed, the Authors demonstrated that the expression of collagen type-I and -II and osteocalcin was higher, whereas the levels of matrix metalloproteases and the BMP inhibitor Noggin were lower in mutated osteoblasts encapsulated in 3D scaffolds compared with control cells [194].…”