Effect on Osteogenic Differentiation of Genetically Modified IL4 or PDGF-BB Over-Expressing and IL4-PDGF-BB Co-Over-Expressing Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro

Abstract

The use of genetically modified (GM) mesenchymal stromal cells (MSCs) and preconditioned MSCs (pMSCs) may provide further opportunities to improve the outcome of core decompression (CD) for the treatment of early-stage osteonecrosis of the femoral head (ONFH). GM interleukin-4 (IL4) over-expressing MSCs (IL4-MSCs), platelet-derived growth factor (PDGF)-BB over-expressing MSCs (PDGF-BB-MSCs), and IL4-PDGF-BB co-over-expressing MSCs (IL4-PDGF-BB-MSCs) and their respective pMSCs were used in this in vitro study and compared with respect to cell proliferation and osteogenic differentiation. IL4-MSCs, PDGF-BB-MSCs, IL4-PDGF-BB-MSCs, and each pMSC treatment significantly increased cell proliferation compared to the MSC group alone. The percentage of Alizarin red-stained area in the IL4-MSC and IL4-pMSC groups was significantly lower than in the MSC group. However, the percentage of Alizarin red-stained area in the PDGF-BB-MSC group was significantly higher than in the MSC and PDGF-BB-pMSC groups. The percentage of Alizarin red-stained area in the IL4-PDGF-BB-pMSC was significantly higher than in the IL4-PDGF-BB-MSC group. There were no significant differences in the percentage of Alizarin red-stained area between the MSC and IL4-PDGF-BB-pMSC groups. The use of PDGF-BB-MSCs or IL4-PDGF-BB-pMSCs increased cell proliferation. Furthermore, PDGF-BB-MSCs promoted osteogenic differentiation. The addition of GM MSCs may provide a useful supplementary cell-based therapy to CD for treatment of ONFH.

The efficiency of genetically modified mesenchymal stromal cells combined with a functionally graded scaffold for bone regeneration in corticosteroid‐induced osteonecrosis of the femoral head in rabbits

“…First, the results obtained using the current model in rabbits may differ from those in humans with ONFH 68 . Second, although we did not present in vitro data for the PDGF‐MSCs or IL‐4‐PDGF‐pMSCs in the current study, our previous in vitro reports using the same cells have demonstrated the efficacy of these MSCs 31 . Third, it is possible that the sample size was small in this study.…”

“…Due to this early negative effect of IL‐4 on osteogenesis, we found that administration of IL‐4‐MSCs prevented osteogenesis in vivo 17 . Therefore, we created novel IL‐4‐PDGF‐MSCs and anticipated that PDGF‐BB from IL4‐PDGF‐pMSCs might overcome the potential negative effects of IL‐4 on bone formation and the initial inflammation required for it 31 . However, it was not observed in our results that PDGF‐BB could overcome the early negative effect of IL‐4 in vivo, explaining the inferior bone formation of the IL‐4‐PDGF‐pMSCs compared to the CD alone.…”

“…Therefore, we conducted in vitro studies to determine which GM MSCs and pMSCs were optimal. Consequently, we examined the efficacy of IL‐4‐MSCs, PDGF‐MSCs, and IL‐4‐PDGF‐MSCs and each preconditioned MSCs as an adjunct treatment for CD 31 . PDGF‐MSCs increased cell proliferative capacity and osteogenic ability.…”

“…Consequently, we examined the efficacy of IL-4-MSCs, PDGF-MSCs, and IL-4-PDGF-MSCs and each preconditioned MSCs as an adjunct treatment for CD. 31 This study examines the efficacy of an adjunct treatment of CD using PDGF-MSCs or IL-4-PDGF-pMSCs with 30% porosity FGS for treating a rabbit steroid-induced ONFH model using CD. It was hypothesized that the combined effect of these GM MSCs or pMSCs with the FGS would be superior to the effect of each treatment alone.…”

Emerging roles of growth factors in osteonecrosis of the femoral head

“…In addition, PDGF-BB has beneficial immunomodulatory effects ( Zhang J. M. et al, 2016 ). Owing to the pleiotropy of PDGF-BB, some scholars have used it for the treatment of ONFH ( Tsubosaka et al, 2021 ). Guzman et al (2021) transduced MSCs with a lentiviral vector carrying the human PDGF-BB gene under the control of the phosphoglycerate (PGK) promoter and assessed the proliferative rate, PDGF-BB expression, and osteogenic differentiation capacity in vitro .…”