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The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits
- Source :
- Stem Cell Research & Therapy, Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-17 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- BackgroundApproximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH.MethodsIn vitro studies:Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed.ResultsIn vitro studies:PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P P P P P = 0.07) than CMV-PDGF-BB-MSCs. In vivo:The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P P P ConclusionThe use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.
- Subjects :
- Decompression
Male
Medicine (General)
Core decompression
Angiogenesis
medicine.medical_treatment
Becaplermin
Medicine (miscellaneous)
QD415-436
Rabbit
Biochemistry
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Andrology
R5-920
Femur Head Necrosis
Osteogenesis
In vivo
Osteoclast
Animals
Humans
Medicine
Bone regeneration
Femoral head
Bone mineral
Hip
business.industry
Research
Growth factor
Mesenchymal stem cell
Osteonecrosis
Femur Head
Mesenchymal Stem Cells
Cell Biology
medicine.anatomical_structure
Regenerative medicine
Adjunctive treatment
Molecular Medicine
Steroids
Rabbits
business
Subjects
Details
- ISSN :
- 17576512
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....6128100e12c792bd767ebf2f95c553cc