Management of knee osteoarthritis by combined stromal vascular fraction cell therapy, platelet-rich plasma, and musculoskeletal exercises: a case series

Nathan Gibbs,1 Rod Diamond,2 Eric O Sekyere,3 Wayne D Thomas4 1South Sydney Sports Medicine, Kensington, 2Diamond Health Care, Kensington, 3Endeavour College of Natural Health, Sydney, 4Cell-Innovations Pty Ltd, Liverpool, NSW, Australia Introduction: Knee osteoarthritis is associated with persistent joint pain, stiffness, joint deformities, ligament damage, and surrounding muscle atrophy. The complexity of the disease makes treatment difficult. There are no therapeutic drugs available to halt the disease progression, leaving patients dependent on pain medication, anti-inflammatory drugs, or invasive joint replacement surgery. Case presentations: Four patients with a history of unresolved symptomatic knee osteoarthritis were investigated for the therapeutic outcome of combining an exercise rehabilitation program with intra-articular injections of autologous StroMed (ie, stromal vascular fraction cells concentrated by ultrasonic cavitation from lipoaspirate) and platelet-rich plasma (PRP). The Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) was administered along with physical function tests over a 12-month period. The first patient achieved a maximum therapeutic outcome of 100 in all five KOOS subscales (left knee), and 100 for four subscales (right knee). The second patient scored 100 in all five KOOS subscales (left knee), and greater than 84 in all subscales (right knee). Treatment of the third patient resulted in improved outcomes in both knees of >93 for four KOOS subscales, and 60 for the Function in Sport and Recreation subscale. The fourth patient improved to 100 in all five KOOS subscales. In all patients, the physical function “Get-up and Go” test and “Stair Climbing Test” returned to normal (a value of zero). Conclusion: This case series indicates that improved outcomes may be obtained when autologous stromal vascular fraction (StroMed) cell therapy is combined with traditional exercise practices and PRP for osteoarthritis. Of the seven joints treated: all patients’ scores of pain improved to >96; and quality of life scores to >93. Functional performance measures of mobility returned to normal. This simple treatment appears to be extremely effective for osteoarthritis disorders that have no drug treatment to halt disease progression. Keywords: autologous stromal cell concentrate, SVF, StroMed, mesenchymal stem cells, pain, join

Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis.

The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor initiation, and progressively increased to meet the demands of tumorigenesis. A corresponding increase in the expression of genes involved in ribosomal biogenesis suggested that MYCN-driven transactivation of the protein biosynthetic machinery generated the necessary substrates to drive glutathione biosynthesis. Pre-malignant sympathetic ganglia from TH-MYCN mice had higher antioxidant capacity and required glutathione upregulation for cell survival, when compared to wildtype ganglia. Moreover, in vivo administration of inhibitors of glutathione biosynthesis significantly delayed tumorigenesis when administered prophylactically and potentiated the anticancer activity of cytotoxic chemotherapy against established tumors. Together these results identify enhanced glutathione biosynthesis as a selective metabolic adaptation required for initiation of MYCN-driven neuroblastoma, and suggest that glutathione-targeted agents may be used as a potential preventative strategy, or as an adjuvant to existing chemotherapies in established disease