Abstract <p>Schwann cells are emerging as modulators of tissue regeneration and are a source of paracrine neurotrophic cues.&#xa0;To assess whether Schwann-cell–derived soluble factors can shape osteoprogenitor function in an engineering-relevant system, we used a transwell co-culture platform of SW10 Schwann cells and MC3T3-E1 pre-osteoblasts that supports paracrine signaling without direct cell–cell contact.&#xa0;Following co-culture, MC3T3-E1 cells had enhanced alkaline phosphatase (ALP) activity and upregulated expression of the mid-stage osteogenic marker Spp1, and there was a modest increase in metabolic activity consistent with improved cell viability.&#xa0;To assess if a defined, tunable neurotrophic input could recapitulate these Schwann-cell co-culture responses, we next examined nerve growth factor (NGF) in a quantitative dose–response analysis.&#xa0;Very low doses of NGF (5&#xa0;pg/mL) were sufficient to increase ALP activity and drive osteogenic gene expression and matrix mineralization, closely recapitulating the effects of the Schwann cell co-culture system.&#xa0;This study demonstrates that physiologically low levels of neurotrophic signaling are sufficient to modulate osteoprogenitor activity and provides complementary cell-based and factor-based strategies for incorporating neural cues into bone regenerative engineering.</p> Lay Summary <p>Bone regeneration is influenced not only by biochemical and mechanical signals, but also by communication with the nervous system. In this study, we demonstrate two complementary strategies to engage neural-associated signaling in bone-forming cells: co-culture with Schwann cells and treatment with very low levels of nerve growth factor (NGF). Both approaches enhance osteogenic cellular activity through soluble paracrine cues. These findings provide practical design strategies for incorporating neurotrophic signaling into bone regenerative engineering.</p>

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Cell-Based and Factor-Based Strategies for Engaging Neuro–Osteogenic Signaling in Osteoprogenitor Cells

  • Ho-Man Kan,
  • Taraje Whitfield,
  • Kevin W.-H. Lo

摘要

Abstract

Schwann cells are emerging as modulators of tissue regeneration and are a source of paracrine neurotrophic cues. To assess whether Schwann-cell–derived soluble factors can shape osteoprogenitor function in an engineering-relevant system, we used a transwell co-culture platform of SW10 Schwann cells and MC3T3-E1 pre-osteoblasts that supports paracrine signaling without direct cell–cell contact. Following co-culture, MC3T3-E1 cells had enhanced alkaline phosphatase (ALP) activity and upregulated expression of the mid-stage osteogenic marker Spp1, and there was a modest increase in metabolic activity consistent with improved cell viability. To assess if a defined, tunable neurotrophic input could recapitulate these Schwann-cell co-culture responses, we next examined nerve growth factor (NGF) in a quantitative dose–response analysis. Very low doses of NGF (5 pg/mL) were sufficient to increase ALP activity and drive osteogenic gene expression and matrix mineralization, closely recapitulating the effects of the Schwann cell co-culture system. This study demonstrates that physiologically low levels of neurotrophic signaling are sufficient to modulate osteoprogenitor activity and provides complementary cell-based and factor-based strategies for incorporating neural cues into bone regenerative engineering.

Lay Summary

Bone regeneration is influenced not only by biochemical and mechanical signals, but also by communication with the nervous system. In this study, we demonstrate two complementary strategies to engage neural-associated signaling in bone-forming cells: co-culture with Schwann cells and treatment with very low levels of nerve growth factor (NGF). Both approaches enhance osteogenic cellular activity through soluble paracrine cues. These findings provide practical design strategies for incorporating neurotrophic signaling into bone regenerative engineering.