Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model

<p>Abstract</p> <p>Background</p> <p>This work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys).</p> <p>Methods</p> <p>Twenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin-B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell-treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test.</p> <p>Results</p> <p>The reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior.</p> <p>Conclusions</p> <p>Homing was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis.</p

Knowledge about stroke among adults in Sharjah, United Arab Emirates

Background: In UAE, stroke is the second leading cause of disability after RTA, where annually 8,000 to 10,000 patients get a stroke. Our aim is to identify the knowledge levels of stroke among Sharjah’s adult citizens.Methods: Using self-administered questionnaires, in a cross-sectional design, a non-probability convenience sampling method was used to enrol subjects. Eligible subjects were above 18 years of age, comprehended Arabic or English, and are currently residing in Sharjah. The questionnaire was 17 questions structured in 5 sections which included: demographics, general knowledge, knowledge of signs and symptoms, risk factors, and appropriate response towards stroke. SPSS V.22 was used to analyse the data. Percentages, means, and ANOVA were used. A P-value less than 0.05 was considered to be statistically significant.Results: The study included 426 subjects, mean age was 35.1 years, 65.2% were females. 51.8% of the subjects claimed they know what stroke is, out of whom 24.3% provided incorrect descriptions. The mean knowledge level of signs and symptoms was 55.4%, and of risk factors was 40.6%. Visual disturbance was the least identified of the five signs and symptoms (38.0%). Female gender, African American race, and age above 60, were the least identified of the 8 risk factors (4.7%, 3.5%, 19.8% respectively). Better knowledge was associated with increased age and higher education. Conclusion: The majority of the sample showed an average to low level of knowledge. Such results indicate the importance of implementing more awareness programs that target younger age groups in the community

Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release

Aims: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results: Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and procalcific potential of microcalcification

Effect of combined intrathecal/intravenous injection of bone marrow derived stromal cells in platelet rich plasma on spinal cord injury in companion animals

Background: Companion animals are prone to spinal cord injuries commonly associated with severe locomotor and sensory complications, which can escalate to a state of irreversible paralysis. Stem cell therapies propose a hope for treating spinal cord injuries via differentiation into neurons and associated glial cells, halting the immune attacks, inhibiting apoptosis and necrosis, and secretion of neurotrophic factors that stimulate the regeneration process. Aim: The study aims to evaluate the use of autologous bone marrow derived stromal cells in Platelet Rich Plasma carrier for selected clinical cases having chronic spinal cord injuries in dogs and cats via a one-time combined intrathecal/intravenous injection. Methods: Cells were injected in 5 dogs and 3 cats suffering from disc protrusion leading to spinal cord injury and in thosewho did not respond to conventional treatment during a clinical trial. Results: Results indicated that the transplanted cells led to the restoration of the weight bearing locomotor function and spinal reflexes in a period less than 90 days with physical rehabilitation. The treatment showed minor changes in the magnetic resonance images of extruded discs. Conclusion: This study concluded that the combined intrathecal/intravenous injection of bone marrow stromal cells is a safe and promising procedure for treating chronic spinal cord injuries in companion animals

Comparison between stem cell therapy and stem cell derived exosomes on induced multiple sclerosis in dogs

Abstract Background Multiple sclerosis (MS) is a chronic condition that primarily manifests as demyelination of neuronal axons in the central nervous system, due to the loss or attack of oligodendroglia cells that form myelin. Stem cell therapy has shown promising results for the treatment of MS due to its capability to halt the immune attack, stop apoptosis and axonal degeneration, and differentiate into oligodendrocytes. Stem cell-derived Exosomes (Exosomes) have shown great capabilities for neuronal diseases as they have growth factors, complex sets of miRNA, enzymes, proteins, major peptides, lipids, and macromolecules with anti-inflammatory, angiogenesis, and neurogenesis activities. Methods This study aimed to compare the healing properties of stem cells, against Exosomes for the treatment of an experimentally induced MS dog model. Dog models of MS received either a single treatment of stem cells or a single treatment of Exosomes intrathecally and the treatment process was evaluated clinically, radiologically, histopathologically, and electron microscopy and cerebrospinal fluid analysis. Results showed marked amelioration of the clinical signs in both treated groups compared to the control one, magnetic resonance scans showed the resolution of the hyperintense lesions at the end of the study period, the histopathology and electron microscopy showed marked healing properties and remyelination in treated groups with superiority of the stem cells compared to Exosomes. Conclusions Although stem cell results were superior to Exosomes therapy; Exosomes have proven to be effective and safe important actors in myelin regeneration, and their use in diseases like MS helps to stimulate remyelination

Effect of combined intrathecal/intravenous injection of bone marrow derived stromal cells in platelet-rich plasma on spinal cord injury in companion animals

Background: Companion animals are prone to spinal cord injuries commonly associated with severe locomotor and sensory&nbsp; complications, which can escalate to a state of irreversible paralysis. Stem cell therapies propose a hope for treating spinal cord injuries via differentiation into neurons and associated glial cells, halting the immune attacks, inhibiting apoptosis and necrosis, and secretion of neurotrophic factors that stimulate the regeneration process. Aim: The study aims to evaluate the use of autologous bone marrow derived stromal cells in platelet-rich plasma carrier for selected clinical cases having chronic spinal cord injuries in dogs and cats via a one-time combined intrathecal/ intravenous injection. Methods: Cells were injected in five dogs and three cats suffering from disc protrusion leading to spinal cord injury and in thosewho did not respond to conventional treatment during a clinical trial. Results: Results indicated that the transplanted cells led to the restoration of the weight bearing locomotor function and spinal reflexes in a period less than 90 days with physical rehabilitation. The treatment showed minor changes in the magnetic resonance images of&nbsp; extruded discs. Conclusion: This study concluded that the combined intrathecal/intravenous injection of bone marrow stromal cells is a safe and promising procedure for treating chronic spinal cord injuries in companion animals

Involvement of the α7-nicotinic acetylcholine receptors in the anti-inflammatory action of the thymulin-related peptide (PAT)

Background and Purpose: Peptide analog of thymulin (PAT) has been shown to have anti-hyperalgesic and anti-inflammatory properties in animal models of inflammation. Recent reports suggest that the peripheral cholinergic system has an anti-inflammatory role mediated by α7-nicotinic acetylcholine receptor (α7-nAChR). Our aim is to investigate whether the action of PAT is mediated, via the cholinergic pathway. Experimental Approach: The anti-hyperalgesic and anti-inflammatory action of PAT was assessed in rat models of inflammatory nociceptive hyperactivity (carrageenan and endotoxin) and in a mice air-pouch model for localized inflammation, respectively; the possible attenuation of PAT\u27s effects by pretreatment with the α7-nAchR specific antagonist methyllycaconitine citrate (MLA) was also investigated. In another series of experiments, using two electrode recordings, the effect of PAT on the α7-nAChRs, expressed in Xenopus Oocytes, was also determined. Key Results: Administration of PAT reversed inflammatory nociceptive hyperactivity and cold and tactile hyperactivity in rats. This effect was partially or totally prevented by MLA, as assessed by different behavioral pain tests. Treatment with PAT also reduced the alteration of cytokines and NGF levels by carrageenan injection in the mouse air pouch model; this effect was partially antagonized by MLA. Electrophysiological recording demonstrated that PAT significantly potentiated the α7-nAchR expressed in Xenopus Oocytes. These effects were not observed when a control peptide, with a reverse sequence (rPAT), was utilized. Conclusions and Implications: The behavioral and electrophysiological observations described in this report demonstrate that PAT mediates, at least partially, its anti-inflammatory action by potentiating the α7-nAChR. These results indicate that PAT has a potential for new therapeutic applications as anti-inflammatory and analgesic agent. © 2013 IBRO