Osteogenic Differentiation Influences Stem Cell Migration Out of Scaffold-Free Microspheres

Abstract

Complete bone regeneration of critical-size defects frequently fail because of the use of acellular bone substitutes and because of partially negative influences of artificial scaffolds. However, the supply of cells to critical-size defects is essential for the regeneration. Therefore, engineered scaffold-free tissues, with outgrowing cells that fill up spaces in the bony defect, are promising candidates for bone regeneration approaches. Here, we demonstrate such a scaffold-free tissue construct (microspheres) that, if osteogenic differentiated, mineralizes while maintaining the capability to let cells grow out of the united cell structure. A superior outgrowth capability of microspheres composed of human cord blood-derived unrestricted somatic stem cells compared with murine embryonic stem cells was found and a time-dependent reduction in outgrowth was evident in vitro. Even after 5 days of osteoinduction and strong mineralization, the cells migrate out of the microsphere. As migration of cells out of unrestricted somatic stem cell microspheres was also found in extracellular matrix gel, we suggest that cells would migrate also in vivo. Thus, microspheres could serve as the scaffold and the source of osteogenic cells in future bone regeneration approaches. Further, microspheres permit the precise administration of large amount of cells into an area of interest.

Effective combination of aligned nanocomposite nanofibers and human unrestricted somatic stem cells for bone tissue engineering

“…Furthermore, their use does not raise ethical concerns [2,33,34] . The differentiation potential of USSCs into the osteogenic lineage is well known and has been verified by many research groups [36,40,41] . They can be differentiated into the osteogenic lineage both spontaneously and when cultured with specific supplements [36] .…”

“…The differentiation potential of USSCs into the osteogenic lineage is well known and has been verified by many research groups [36,40,41] . They can be differentiated into the osteogenic lineage both spontaneously and when cultured with specific supplements [36] . The control of osteogenic differentiation of USSCs is important for in vitro culture or delivery by matrices.…”

“…This adherent HLA class II and CD45-negative stem cell can be stimulated to differentiate into bone, cartilage, hematopoietic cells, neural cells, liver and heart [2,34] . It is worth noting that spontaneous differentiation of USSCs into osteoblasts has been demonstrated [36] . As a result, a USSC-based tissue engineering strategy seems to be an ideal approach for bone regeneration.…”

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

“…144 Moreover, the time for osteogenic priming was inversely related to the cell outgrowth from the aggregate. 145,146 In vivo studies in rabbits showed that aggregates of MSCs could adhere promptly on the osteochondral defects by surface tension and stay without any loss, improving cartilage regeneration. 22 Aggregate composites of chondrocytes and synovium-derived MSCs were injected to the osteochondral defects in a rabbit model, and effective restoration of articular cartilage and in vivo ECM production were observed.…”

Stem Cell Regenerative Therapy in Oral and Maxillofacial Region: A Systematic Review.

“…Use of skeletal or dental stem cells can be used in future to repair craniofacial region and may provide a promising alternative approach for reconstruction of craniofacial defects. Lagenbach et al2010 (43) in their in vitro studies used microspheres (scaffold free tissue construct) to close the bone defects. They found osteogenically differentiated microspheres with outgrowing cells can be used to fill up bone defects.…”