The terms 'antioxidant', 'oxidative stress' and 'oxidative damage' are widely used but rarely defined. This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.

Biochemistry of oxidative stress

The objective of this study was to compare the clinical efficacy of repeated doses of leucocyte-poor platelet-rich plasma (LP-PRP) plus hyaluronic acid (HA) to a single dose of autologous microfrag...

A Prospective Study Comparing Leukocyte-Poor Platelet-Rich Plasma Combined with Hyaluronic Acid and Autologous Microfragmented Adipose Tissue in Patients with Early Knee Osteoarthritis.

To evaluate the effects of eccentric strengthening exercises (ESE) in athletic patients with Achilles tendinopathy. Forty five athletic patients (29 men, average age 26 years; 16 women, average age 28 years; average height: 173 ± 16.8, range 158 to 191; average weight 70.8 kg ± 15.3, range 51.4 to 100.5) with clinical diagnosis of unilateral tendinopathy of the main body of the Achilles tendon completed the VISA-A questionnaire at first attendance and at their subsequent visits. The patients underwent a graded progressive eccentric calf strengthening exercises programme for 12 weeks. The mean pre-management VISA-A scores of 36 (SD 23.8; 95% C.I.: 29 – 46) improved to 52 (SD 27.5; 95% C.I.: 41.3 – 59.8) at the latest follow up (p = 0.001). Twenty seven of the 45 patients responded to the eccentric exercises. Of the 18 patients who did not improve with eccentric exercises, 5 (mean age: 33 years) improved with two peritendinous aprotinin and local anaesthetic injections. 10 of the 18 patients (9 men, mean age 35 years; 1 woman aged 40 years) who did not improve with eccentric exercises and aprotinin injections proceeded to have surgery. The remaining three patients (3 women, mean age 59.6 years; 2 men, mean age 63 years) of the 18 non-responders to eccentric exercises and aprotinin injections declined surgical intervention. ESE in athletic patients provide comparable clinical outcome compared to our previous results in non-athletic patients. ESE are a viable option for the management of AT in athletes, but, in our hands, only around 60% of our athletic patients benefited from an intensive, heavy load eccentric heel drop exercise regimen alone. If ESE fail to improve the symptoms, aprotinin and local anaesthetic injections should be considered. Surgery is indicated in recalcitrant cases after 3 to 6 months of non operative management.

Eccentric calf muscle training in athletic patients with achilles tendinopathy

Introduction Over the past decade, human adipose-derived mesenchymal stem/signaling/stromal cell (ADSC) therapies have become increasingly popular as a biologic treatment for a variety of orthopedic conditions. ADSCs represent a source of stromal cells with biologic properties that allow for paracrine and immunomodulatory functions and the ability to differentiate into various downstream cellular tissues. Before considering the use of adipose tissue as a cellular source, it is imperative to understand its anatomy and physiology and its roles in the human body. Objectives To review the current literature regarding the anatomy, physiology, and various roles of human adipose tissue, as well as harvesting techniques and its role in biologic therapy. Methods A comprehensive literature review that included searches of PubMed, medline, EMBASE, and Google Scholar database(s), including both preclinical and clinical studies, was performed. Results This manuscript represents an updated understanding of adipose tissue, including its anatomy, functions in the human body, and role as a perivascular cellular source for tissue renewal, in addition to its role in providing cushioning and support to various structures. Conclusion Adipose tissue is widespread throughout the body and serves multiple physiologic functions. It can be harvested through several techniques and is an abundant source of bioactive molecules and ADSCs. Research in orthopedic surgery has begun using adipose tissue as a source of homologous and non-homologous cell and tissue applications. Future study will continue to investigate optimal sources of adipose-derived cells and tissues, and its therapeutic applications in orthopedics.

The essential roles of human adipose tissue: Metabolic, thermoregulatory, cellular, and paracrine effects

With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source. The three primary sources include the placenta, bone marrow, and adipose tissue, all of which offer excellent safety profiles. The primary mechanisms of action are trophic and immunomodulatory effects, which prevent the further degradation of joints. However, the function and degree to which benefits are observed vary significantly based on the exosomes secreted by MSCs. Paracrine and autocrine mechanisms prevent cell apoptosis and tissue fibrosis, initiate angiogenesis, and stimulate mitosis via growth factors. MSCs have even been shown to exhibit antimicrobial effects. Clinical results incorporating clinical scores and objective radiological imaging have been promising, but a lack of standardization in isolating MSCs prevents their incorporation in current guidelines.

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Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review

The aim of this study is to evaluate the outcomes of autologous microfragmented adipose tissue (MFAT) injection in elderly patients with knee osteoarthritis (OA). We hypothesized that MFAT knee infiltration for the treatment of knee OA would yield good clinical results out to two years follow-up. Multi-centric, international, open-label study conducted by orthopedic surgery, and/or regenerative medicine facilities utilizing patient registries. Subjects recruited for eligibility. The primary outcome measure was Knee Injury and Osteoarthritis Outcome Score (KOOS). Outcomes and patient factors were compared to baseline, at six, 12, and 24 months. Statistical models were used to assess KOOS subscores and probability of exceeding the Minimally Clinically Important Difference (MCID) or Patient Acceptable Symptom State (PASS), and to assess the effect of the treatment variables on KOOS - Pain. Seventy-five patients, 120 primary treatments, mean age 69.6 years, (95%CI 68.3–70.9), BMI 28.4 (95%CI 27.3–29.6), with KL grade 2 to 4 knee OA treated with a single MFAT injection. KL grades 2 (15.1%), 3 (56.3%), and 4 (28.6%), with 20.8% of knees having previously undergone surgery. Patients with KL grade 2 disease had the best results in KOOS - Pain (P = 0.001), at six, 12, and 24 months. Including advanced KL grade 3 and 4 osteoarthritis patients, significant functional and quality of life success was seen in 106/120 treatments (88.3%, 66 patients) at all follow-up time points. Fourteen treatments (11.7%, 9 patients) failed prior to the study endpoint. This study shows that a single-dose MFAT injection leads to clinical, functional, and quality of life improvement at two years in elderly patients, in KL grades 2 to 4 of knee osteoarthritis. These findings provide evidence that this treatment modality could be a safe and effective option to other commonly available treatments in carefully selected patients.

Two-year clinical outcomes of autologous microfragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study

The doctor of the future will give no medicine, but will interest his patients in the care of the human frame, in a proper diet, and in the cause and prevention of disease.

—Thomas Edison (1847–1931)

The Optimization of Natural Healing

BackgroundTo evaluate changes in pain, function, and quality of life after treatment with injected micro-fragmented adipose tissue (MFAT) for knee osteoarthritis in a large cohort of individuals treated at multiple centers.
MethodsOne hundred ten individuals were recruited from three private outpatient clinics. Participants had to be diagnosed with symptomatic knee OA (defined by persistent knee pain associated with clinical symptoms of OA and/ or classic imaging findings) and who had not received prior knee surgery or treatment with platelet-rich plasma, cortisone, or hyaluronic acid within the previous 6 weeks. Data from 120 knees were included in the analysis. Outcome measures included Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales (pain, symptoms, activities of daily living [ADL], sports and recreation, quality of life [QOL]) and an 11-point Numerical Rating Scale (NRS) for average knee pain over the past week. Outcomes were collected at baseline and 3, 6, and 12 months.
ResultsSignificant increases and decreases in KOOS subscale and NRS scores were observed, respectively, in the cohort as a whole (p< .05). Lower BMI was associated with more significant improvements in pain, sports/recreation, and ADL KOOS subscale scores (p< .05). Greater age was associated with more significant improvements in symptoms and QOL subscale scores (p< .05).
ConclusionsA single injection of MFAT improved pain, function, and QOL outcome measures up to 12 months in this cohort for more than half of the participants. Greater BMI and lower age negatively influenced outcomes. It is not known whether improvements continue after this timeframe or why many participants reported little-to-no improvement.

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12-Month Cohort Study to Investigate Changes in Patient-Reported Outcomes Pain after Intra-articular Injection of Micro-Fragmented Adipose Tissue for Knee Osteoarthritis

/pdf/response-to-letter-to-the-editor-remarks-on-gobbi-et-al-two-4uw8r8ef6i.pdf

Response to letter to the editor: “Remarks on Gobbi et al.: Two-year clinical outcomes of autologous micro-fragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study”

Christopher Rogers

Papers

Two-year clinical outcomes of autologous microfragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study

The Optimization of Natural Healing

12-Month Cohort Study to Investigate Changes in Patient-Reported Outcomes Pain after Intra-articular Injection of Micro-Fragmented Adipose Tissue for Knee Osteoarthritis

Response to letter to the editor: “Remarks on Gobbi et al.: Two-year clinical outcomes of autologous micro-fragmented adipose tissue in elderly patients with knee osteoarthritis: a multi-centric, international study”