PDGF-BB Over-expressing MSC Gene Therapy for the Teatment of Osteonecrosis of the Femoral Head

Introduction:
Core decompression (CD) is a surgical procedure for early-stage (ARCO stage I and II) osteonecrosis of the femoral head (ONFH) to prevent disease progression and collapse of the femoral head. However, approximately 1/3 of patients subsequently require total hip arthroplasty (THA) after CD. Platelet-derived growth factor (PDGF)-BB plays a central role in many cell growth and differentiation processes. The aim of this study was to characterize and evaluate the therapeutic effect of mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) when injected into the bone tunnel during CD in an in vivo rabbit model of steroid-associated ONFH.

Methods:
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) carrier group, the MSC group, and the PGK-PDGF-BB-MSC group. In the CD group, a 3-mm diameter bone tunnel was created in the left femoral head. In the HG group, HG was injected into the bone tunnel. In the MSC and PGK-PDGF-BB-MSC groups, unmodified MSCs or PGK-PDGF-BB-MSCs were encapsulated in HG and injected into the bone tunnel. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed.

Results:
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 < 0.001), greater osteoclast density (p < 0.01), and greater angiogenesis (p < 0.01) than the other treatment groups. No differences in mechanical tests were noted.

Conclusion:
The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.