Morphogen Delivery by Osteoconductive Nanoparticles Instructs Stromal Cell Spheroid Phenotype
| Autor: | J. Kent Leach, Jacklyn Whitehead, Alefia Kothambawala |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Stromal cell
Biomedical Engineering Bioengineering spheroids Regenerative Medicine Bone morphogenetic protein 2 General Biochemistry Genetics and Molecular Biology Article osteogenesis Biomaterials Stem Cell Research - Nonembryonic - Human BMP-2 Nanotechnology mesenchymal stem/stromal cells stromal cells Transplantation mesenchymal stem biology 5.2 Cellular and gene therapies Chemistry Mesenchymal stem cell Spheroid hydroxyapatite Stem Cell Research Cell biology embryonic structures Osteocalcin biology.protein Alkaline phosphatase bone morphogenetic protein-2 Development of treatments and therapeutic interventions Morphogen |
| Zdroj: | Advanced biosystems, vol 3, iss 12 Adv Biosyst |
| Popis: | Mesenchymal stem/stromal cells (MSCs) exhibit a rapid loss in osteogenic phenotype upon removal of osteoinductive cues, as commonly occurs during transplantation. Osteogenic differentiation can be more effectively but not fully maintained by aggregating MSCs into spheroids. Therefore, the development of effective strategies that prolong the efficacy of inductive growth factors would be advantageous for advancing cell-based therapies. To address this challenge, osteoinductive bone morphogenetic protein-2 (BMP-2) was adsorbed to osteoconductive hydroxyapatite (HA) nanoparticles for incorporation into MSC spheroids. MSC induction was evaluated in osteogenic conditions and retention of the osteogenic phenotype in the absence of other osteogenic cues. HA was more uniformly incorporated into spheroids at lower concentrations, while BMP-2 dosage was dependent upon initial morphogen concentration. MSC spheroids containing BMP-2-loaded HA nanoparticles exhibited greater alkaline phosphatase (ALP) activity and more uniform spatial expression of osteocalcin compared to spheroids with uncoated HA nanoparticles. Spheroids cultured in media containing soluble BMP-2 demonstrated differentiation only at the spheroid periphery. Furthermore, the osteogenic phenotype of MSC spheroids was better retained with BMP-2-laden HA upon the removal of soluble osteogenic cues. These findings represent a promising strategy for simultaneous delivery of osteoconductive and osteoinductive signals for enhancing MSC participation in bone formation. |
| Databáze: | OpenAIRE |
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