In vivo effects of cell seeding technique in an ex vivo regional gene therapy model for bone regeneration.

Autor: Bell JA; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Mayfield CK; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Collon K; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Chang S; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Gallo MC; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Lechtholz-Zey E; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Ayad M; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Sugiyam O; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Tang AH; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA., Park SH; J. Vernon Luck Orthopaedic Research Center, Orthopaedic Institute for Children, Los Angeles, California, USA., Lieberman JR; Department of Orthopaedic Surgery, Keck School of Medicine of USC, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: Journal of biomedical materials research. Part A [J Biomed Mater Res A] 2024 Oct; Vol. 112 (10), pp. 1688-1698. Date of Electronic Publication: 2024 Apr 11.
DOI: 10.1002/jbm.a.37718
Abstrakt: When delivering cells on a scaffold to treat a bone defect, the cell seeding technique determines the number and distribution of cells within a scaffold, however the optimal technique has not been established. This study investigated if human adipose-derived stem cells (ASCs) transduced with a lentiviral vector to overexpress bone morphogenetic protein 2 (BMP-2) and loaded on a scaffold using dynamic orbital shaker could reduce the total cell dose required to heal a critical sized bone defect when compared with static seeding. Human ASCs were loaded onto a collagen/biphasic ceramic scaffold using static loading and dynamic orbital shaker techniques, compared with our labs standard loading technique, and implanted into femoral defects of nude rats. Both a low dose and standard dose of transduced cells were evaluated. Outcomes investigated included BMP-2 production, radiographic healing, micro-computerized tomography, histologic assessment, and biomechanical torsional testing. BMP-2 production was higher in the orbital shaker cohort compared with the static seeding cohort. No statistically significant differences were noted in radiographic, histomorphometric, and biomechanical outcomes between the low-dose static and dynamic seeding groups, however the standard-dose static seeding cohort had superior biomechanical properties. The standard-dose 5 million cell dose standard loading cohort had superior maximum torque and torsional stiffness on biomechanical testing. The use of orbital shaker technique was labor intensive and did not provide equivalent biomechanical results with the use of fewer cells.
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Databáze: MEDLINE