THE EFFICACY OF PRECONDITIONED OR GENETICALLY MODIFIED IL4-SECRETING MESENCHYMAL STROMAL CELLS IN A MODEL OF STEROID-ASSOCIATED OSTEONECROSIS OF THE FEMORAL HEAD IN RABBITS

Introduction

In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits.

Methods

Thirty-six male skeletally mature NZW rabbits received methylprednisolone acetate (20mg/kg) IM once 4 weeks before surgery. There were 6 groups:

1. CD alone – a 3 mm drill hole

   + injection into the CD of:

2. hydrogel (HG) - 200 μl of hydrogel carrier

3. MSCs–1 million rabbit MSCs

4. pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs

5. IL4-MSCs – rabbit IL-4 over-expressing MSCs

6. IL4-pMSCs – preconditioned IL-4 over-expressing MSCs

Eight weeks after surgery, femurs were harvested, and evaluated by microCT, biomechanical, and histological analyses.

Results

Bone mineral density (BMD) and bone volume fraction (BVF) increased in the pMSC group compared to the CD and MSC groups outside of the CD area (p < 0.05, Fig.1). Similarly, the IL4-pMSC group was increased compared to the CD group (p < 0.05). The percentage of empty lacunae in the IL4-MSC group was significantly less than other groups outside the CD area (p < 0.05, Fig.2); however, IL4-MSC group had less trabecular bone formation inside the CD. The mechanical tests demonstrated no differences.

Discussion

This rabbit steroid-associated ONFH model demonstrated that pMSC increased new bone formation after CD; IL4-MSCs that continuously secreted IL-4 decreased the number of empty lacunae . Immunomodulation of bone healing has the potential to improve bone healing after CD for early stage ONFH; these interventions must be applied in a temporally sensitive fashion.

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