Author : Beevi, Syed Sultan
Efficacy of Intra-Articular Injection of Platelet Rich Plasma and Hyaluronic Acid in Early Knee Osteoarthritis Case Series
European Journal of Molecular & Clinical Medicine,
2018, Volume 5, Issue 1, Pages 30-36
Higher prevalence and growing burden of knee Osteoarthritis (OA) combined with recent safety concerns about pharmacological interventions has increased demand for new effective technologies for its management. Need of the hour is an innovative treatment alternative which may repair cartilage damage rather than just reduce symptoms of pain. Hyaluronic acid (HA) and PRP has been shown to relieve pain and symptoms as well as slow the progression of disease as stand-alone therapy. Treatment combining these modalities could be particularly hopeful owing to their positive and diverse interaction among themselves. Combinational treatment using both PRP and HA was performed on a series of 12 patients with early stage primary knee OA who fulfilled all the designated inclusion and exclusion criteria. All the patients were evaluated before and after treatment (1, 3, 6 and 12 months) by physical examination, assessment of VAS for pain, WOMAC, IKDC, KOOS and OKS to record the patient-reported improvement in pain, functionality and quality of life (QOL). 2-tailed Mann Whitney U Test was performed to assess the effect of treatment at different follow-up times of all the clinical scores. Whereas, Pearson correlation coefficient was done to evaluate the correlation between different clinical scores. For all tests, p < 0.05 was considered significant. All patients showed statistically significant improvement in all orthopedics scores evaluated. VAS score was improved significantly from 3.00 ± 0.49 at baseline to 1.57 ± 0.41 (p = 0.031) in Grade I and 3.60 ± 0.51 at baseline to 2.10 ± 0.29 (p = 0.031) in Grade II patients at 6 months follow-up respectively. Other scores followed similar trends with statistically significant improvement at 6 months follow-up which maintained throughout till end of the study period. All patients treated experienced strong functional improvement and substantial gains in pain relief, functionality and QOL. Hence our preliminary findings suggest that combined PRP and HA procedure is safe and potentially efficacious, which merits further investigation in large clinical settings and also in controlled clinical trials with long-term follow-ups. Focal Points Bench side: Platelet Rich Plasma (PRP) deliver a large pool of signalling proteins including growth factors and cytokines to the local milieu driving the tissue regeneration and repair mechanisms which when combined with high molecular weight cross-linked hyaluronan could bestow greater viscoelastic properties and alleviate the symptoms of osteoarthritis. Bedside: Osteoarthritis (OA) is a chronic degenerative disease and there is no cure for OA except medical management and partial/total knee replacement in advanced stage. PRP along with HA could have the therapeutic potential to promote cartilage regeneration and inhibit inflammation synergistically by decreasing the friction coefficient and minimizing wear. Community: The burden of OA on quality of life, disability and health care utilization is quite high. Combined PRP and HA could be an effective single-dose treatment modality restoring the functional activities and considerably reducing effective cost of the treatment. Governments and regulatory agencies: The technology to obtain PRP is FDA-approved and its safety and efficacy has been well established through several clinical studies. Regulatory agencies should consider the evidences put forth by the researchers and sanction grants to investigate in larger clinical settings and also in controlled trials with different ethnicities with long-term follow-ups.
Signal regulatory protein alpha (SIRPA) and kinase domain receptor (KDR) are key expression Markers in cardiac specific precursor selection from hADSCs
European Journal of Molecular & Clinical Medicine,
2015, Volume 2, Issue 4, Pages 93-101
Cardiomyocyte enrichment strategies so far have not yielded scalable cardiac specific cell type. More so, the current data is restricted to embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs), wherein the use of viral vectors is fraught with increased risk during clinical use. Herein, we profiled time-dependent gene/protein expression patterns across the cardiac ectoderm, endoderm, and mesoderm for isolating cardiac precursors from human adipose derived stem cells (hADSC). Methods Direct cardiac differentiation of hADSCs was carried out with 5-azacytidine and basic fibroblast growth factor (bFGF) in a one month long culture. The cells were periodically harvested, analyzed for unique persistent markers and their inherent regulation using quantitative polymerase chain reaction (qPCR), flow cytometry, immunoblot and immunocytochemistry assays. The identified markers were super paramagnetic iron oxide nanoparticle (SPION) tagged for segregation by magnetic activated cell sorting (MACS) and further evaluated their differentiation potential and checked for the purity by flow cytometry.
The results demonstrated pronounced up-regulation of mesodermal and mature cardiac lineage markers at three weeks, while there was a down-regulation of pluripotent stem cell markers. This perhaps could be attributed to de-differentiation in maintaining the cardiac phenotype. However, signal regulatory protein alpha (SIRPA) and kinase domain receptor (KDR) persisted all through the culture period of one month, making them the most relevant and reliable cardiac specific markers. Dual labeling of these markers to SPION for cardiomyocyte enrichment by MACS column yielded cardiomyogenic-like cells in differentiation cultures with several functional positive markers. Conclusions Thus, SIRPA and KDR together provide cues in the enhancement and up-scaling of cardiomyocyte production in the cell replacement therapy. Focal points Benchside Identification of specific cell phenotypic markers to identify cardiac precursors in any tissue source with minimal cell manipulation is a novel process development tool in clinical translation. Bedside A product developed in a closed system would minimize extraneous contaminants in long term cultures and development of such procedures minimizes culture failure rates from bench side. Industry This unique identification of cell-specific marker would enable a tissue-specific translational plan and immensely help in the cardiac regeneration. Government Financial investment and support from the government is vital in the optimization and validation for better health care and would contribute in reducing the disease burden. Regulatory The stringent regulatory guidelines worldwide on minimal cell manipulation for entering into stem cell based clinical trials preclude the need to develop alternate approaches in product and process developmental technology, which can be easily translated in a clinical setup.