Gold-Induced Cytokine (GOLDIC®) Therapy in the Management of Knee Osteoarthritis: An Observational Study.

BACKGROUND: Current treatment modalities for knee osteoarthritis (OA) provide symptomatic cures rather than reversing the pathology in the long term. An innovative regenerative therapy called "Gold Induced Cytokines" (GOLDIC®) was explored in various musculoskeletal diseases such as knee OA, lumbar canal stenosis, Achilles tendinopathy, and plantar fasciitis. In this study, we explored the safety and functional outcome of GOLDIC® injections in knee OA (KL grades 3 and 4) with visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. MATERIALS AND METHODS: A multi-center open-label observational study was carried out after screening the cases according to the inclusion criteria. A total of 106 knees in 65 patients were enrolled for four doses of 4 ml of ultrasound-guided intra-articular GOLDIC® injections every three to six days. All cases were followed up with pre- and post-VAS and WOMAC scores at an interval of four weeks, three months, six months, and one year, and the complications (including severe adverse reactions) were monitored throughout. RESULTS: In this study, 66.1% had grade 4 OA knee (without gross varus or subluxation) and 33.8% had grade 3 OA knee. All the participants underwent the GOLDIC® treatment modality. A statistically significant difference was observed in pre- and post-procedural follow-up in VAS and WOMAC scores at one-year follow-up. There were no recorded severe adverse reactions during the entire study period. Three patients failed the treatment in one year. CONCLUSION: The GOLDIC® procedure shows great promise as a novel method for treating moderate to severe OA of the knee, both in terms of pain and functional outcome without any severe adverse reactions, in a sustained manner and is worth exploring as a long-term treatment option.

Correction: Gold-Induced Cytokine (GOLDIC®) Therapy in the Management of Knee Osteoarthritis: An Observational Study.

[This corrects the article DOI: 10.7759/cureus.46231.].

Correction: Gold-Induced Cytokine (GOLDIC®) Therapy in the Management of Knee Osteoarthritis: An Observational Study.

[This corrects the article DOI: 10.7759/cureus.46231.].

How do I: Evaluate the safety and legitimacy of unproven cellular therapies?

BACKGROUND: Unproven cellular therapies are being offered to patients for a variety of conditions and diseases for which other treatments have failed. The use of untested cellular therapies is a worldwide problem. Practitioners (e.g., physicians, scientists, QA/QI facility managers, and policy advocates) are perhaps unaware of the risks involved with such therapies. Therefore, a critical need exists to bring attention to the potential limitations and adverse effects of these therapies to inform and limit misinformation. STUDY DESIGN AND METHODS: We describe the extent of the unproven cellular therapy problem through a search of scientific literature and social media coverage. We also describe the regulatory framework that can be used by the practitioner to review and evaluate both proven and unproven cellular therapies. RESULTS: We report on the current state of unproven cellular therapies across the globe. A workflow to facilitate an understanding of the regulatory processes involved in the approval of cellular therapies is provided as well as a list of warnings required by regulatory agencies on various products. It is hoped that this article will serve as a tool kit to educate the practitioner on navigating the field of unproven cellular therapy products. DISCUSSION: Increasing awareness of the issues associated with unproven therapies through education is important to help in reducing misinformation and risks to patients.

Bracing NK cell based therapy to relegate pulmonary inflammation in COVID-19.

The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same.

Exosomal therapy-a new frontier in regenerative medicine.

The recent advances in translational and nanomedicine have paved the way for developing the targeted drug delivery system at a greater pace among global researchers. On par with these technologies, exosomes act as a potential portal for cell-free drug delivery systems as these are bestowed with the native characteristics of the parent cell of origin. Exosomes, called extracellular vesicles (EcVs), are present in almost all cells, tissues, and body fluids. They help in intercellular signaling and maintains tissue homeostasis in the disease pathobiology. Researchers have characterized 9,769 proteins, 2,838 miRNAs, 3,408 mRNAs, and 1,116 lipids being present in exosomal cargo. The separation of exosomes from cells, tissues, and body fluids follow different patterned kinetics. Exosomes interact with the recipient cells through their surface receptor molecules and ligands and internalize within recipient cells through micropinocytosis and phagocytosis. Advancing technologies in regenerative medicine have facilitated the researchers to isolate exosomes from mesenchymal stem cells (MSCs) as these cells are blessed with supreme regenerative potentiality in targeting a disease. Exosomal cargo is a key player in establishing the diagnosis and executing therapeutic role whilst regulating a disease process. Various in vitro studies have exhibited the safety, efficacy, and therapeutic potentiality of exosomes in various cancers, neurodegenerative, cardiovascular, and orthopedic diseases. This article throws light on the composition, therapeutic role, and regulatory potentials of exosomes with the widening of the horizon in the field of regenerative medicine.

Concepts in regenerative medicine: Past, present, and future in articular cartilage treatment.

Regenerative medicine is emerging with great interest and hope from patients, industry, academia, and medical professionals. Cartilage regeneration, restoration, or repair is one of the prime targets that remains largely unsolved, and many believe that regenerative medicine can possibly deliver solutions that can be widely used to address the current gap(s) in treatment. In the United States, Europe, Australia, and India the regulation of regenerative based treatments has become a big debate. Although the rules and regulations remain unclear, clinicians that are interested should carry-on with the best available guidelines to ensure safety and compliance during delivery in clinical practice to avoid regulatory infraction. Many have made significant investment of time, resources, and facilities in recent years to provide new regenerative treatment options and advance medical care for patients. Instead of reinventing the wheel, it would be more efficient to adopt currently accepted standards and nomenclature borrowed from transplantation science, and cord blood storage industries. The purposes of this article are to provide some historical background to the field of regenerative medicine as it applies to cartilage, and how this field has developed. This will be followed by a separate discussion on regulatory oversight and input and how it has influenced access to care. Furthermore, we discuss current clinical techniques and progress, and ways to deliver these treatments to patients safely, effectively, and in a cost sensitive manner, concluding with an overview of some of the promising regenerative techniques specific to cartilage.