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Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_10 | Pages 6 - 6
1 Oct 2020
Maruyama M Moeinzadeh S Guzman RA Takagi M Yang YP Goodman SB
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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:. CD alone – a 3 mm drill hole. + injection into the CD of:. hydrogel (HG) - 200 μl of hydrogel carrier. MSCs–1 million rabbit MSCs. pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs. IL4-MSCs – rabbit IL-4 over-expressing MSCs. 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. For any figures, tables, or references, please contact the authors directly


Bone & Joint Research
Vol. 11, Issue 12 | Pages 881 - 889
1 Dec 2022
Gómez-Barrena E Padilla-Eguiluz N López-Marfil M Ruiz de la Reina R

Aims

Successful cell therapy in hip osteonecrosis (ON) may help to avoid ON progression or total hip arthroplasty (THA), but the achieved bone regeneration is unclear. The aim of this study was to evaluate amount and location of bone regeneration obtained after surgical injection of expanded autologous mesenchymal stromal cells from the bone marrow (BM-hMSCs).

Methods

A total of 20 patients with small and medium-size symptomatic stage II femoral head ON treated with 140 million BM-hMSCs through percutaneous forage in the EudraCT 2012-002010-39 clinical trial were retrospectively evaluated through preoperative and postoperative (three and 12 months) MRI. Then, 3D reconstruction of the original lesion and the observed postoperative residual damage after bone regeneration were analyzed and compared per group based on treatment efficacy.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 340 - 347
22 Apr 2022
Winkler T Costa ML Ofir R Parolini O Geissler S Volk H Eder C

Aims

The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

Methods

HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 106 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty. Patients will be followed for two years. The primary endpoint is the Short Physical Performance Battery (SPPB) at week 26. Secondary and exploratory endpoints include morphological parameters (lean body mass), functional parameters (abduction and handgrip strength, symmetry in gait, weightbearing), all-cause mortality rate and patient-reported outcome measures (Lower Limb Measure, EuroQol five-dimension questionnaire). Immunological biomarker and in vitro studies will be performed to analyze the PLX-PAD mechanism of action. A sample size of 240 subjects was calculated providing 88% power for the detection of a 1 SPPB point treatment effect for a two-sided test with an α level of 5%.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 751 - 759
1 Jul 2023
Lu V Andronic O Zhang JZ Khanduja V

Aims

Hip arthroscopy (HA) has become the treatment of choice for femoroacetabular impingement (FAI). However, less favourable outcomes following arthroscopic surgery are expected in patients with severe chondral lesions. The aim of this study was to assess the outcomes of HA in patients with FAI and associated chondral lesions, classified according to the Outerbridge system.

Methods

A systematic search was performed on four databases. Studies which involved HA as the primary management of FAI and reported on chondral lesions as classified according to the Outerbridge classification were included. The study was registered on PROSPERO. Demographic data, patient-reported outcome measures (PROMs), complications, and rates of conversion to total hip arthroplasty (THA) were collected.