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.

Abstract

Core decompression (CD) with mesenchymal stromal cells (MSCs) is an effective therapy for early-stage osteonecrosis of the femoral head (ONFH). Preconditioning of MSCs, using inflammatory mediators, is widely used in immunology and various cell therapies. We developed a three-dimensional printed functionally graded scaffold (FGS), made of β-TCP and PCL, for cell delivery at a specific location. The present study examined the efficacy of CD treatments with genetically modified (GM) MSCs over-expressing PDGF-BB (PDGF-MSCs) or GM MSCs co-over-expressing IL-4 and PDGF-BB and preconditioned for three days of exposure to lipopolysaccharide and tumor necrosis factor-alpha (IL-4-PDGF-pMSCs) using the FGS for treating steroid-induced ONFH in rabbits. We compared CD without cell-therapy, with IL-4-PDGF-pMSCs alone, and with FGS loaded with PDGF-MSCs or IL-4-PDGF-pMSCs. For the area inside the CD, the bone volume in the CD alone was higher than in both FGS groups. The IL-4-PDGF-pMSCs alone and FGS + PDGF-MSCs reduced the occurrence of empty lacunae and improved osteoclastogenesis. There was no significant difference in angiogenesis among the four groups. The combined effect of GM MSCs or pMSCs and the FGS was not superior to the effect of each alone. To establish an important adjunctive therapy for CD for early ONFH in the future, it is necessary and essential to develop an FGS that delivers biologics appropriately and provides structural and mechanical support.

• Authors: Masanori Tsubosaka, Masahiro Maruyama, Elaine Lui, Seyedsina Moeinzadeh, Elijah Ejun Huang, Junichi Kushioka, Hirohito Hirata, Charu Jain, Hunter W Storaci, Calvin Chan, Masakazu Toya, Qi Gao, Victoria Teissier, Huaishuang Shen, Xueping Li, Ning Zhang, Tomoyuki Matsumoto, Ryosuke Kuroda, Stuart B Goodman, Yunzhi Peter Yang
• Journal: Journal of biomedical materials research. Part A (J Biomed Mater Res A) Vol. 111 Issue 8 Pg. 1120-1134 (08 2023) ISSN: 1552-4965 [Electronic] United States
• PMID: 36606330 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2023 Wiley Periodicals LLC.

Chemical References

• Becaplermin
• Interleukin-4
• Adrenal Cortex Hormones

Topics

• Animals
• Rabbits
• Femur Head (pathology, surgery)
• Becaplermin
• Interleukin-4 (pharmacology)
• Bone Regeneration
• Mesenchymal Stem Cells (pathology)
• Adrenal Cortex Hormones (pharmacology)
• Osteonecrosis (chemically induced, therapy, pathology)