The best of both worlds: In vitro evaluation of combining two stem cell types for true cardiac repair

Abstract

INTRODUCTION: Bone healing can be augmented by pre-conditioning MSCs (pMSCs) with inflammatory cytokines. Another approach is timely resolution of inflammation using immunomodula-tory cytokines. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on early stage steroid-associated osteonecrosis of the femoral head (ONFH) in rabbits .METHODS: 36 male mature NZW rabbits received methylpred-nisolone acetate (20mg/kgIM) 4 weeks before surgery. There were 6 groups: 1. Core Decompress (CD) alone-a 3 mm drill hole+ injection of:2. hydrogel (HG)-200 ml of hydrogel carrier3. MSCs-1 million rabbit MSCs4. pMSC-LPS (20 mg/ml) + TNFa (20 ng/ml) precondi-tioned MSCs 5. IL4-MSCs-rabbit IL-4 over-expressing MSCs 6. IL4-pMSCs-preconditioned IL-4 over-expressing MSCsEight weeks after surgery, femurs were evaluated by microCT, biomechanical, and his-tological analyses.RESULTS: Bone mineral density (BMD) and bone volume fraction (BVF) increased outside the CD in the pMSC group compared to the CD and MSC groups (p < 0.05). 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 (p < 0.05); however, IL4-MSC group had less trabecular bone formation inside the CD. DISCUSSION: pMSC increased new bone formation after CD in ONFH; IL4-MSCs 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.