ObjectivesIn this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model.MethodsOsteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2×107 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium.ResultsThe proliferation rate of ADSCs 34.4±1.6 hr was significantly higher than that of the BMSCs 48.8±5.3 hr (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9.ConclusionAutologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

The dynamic nature of modern warfare, including threats and injuries faced by soldiers, necessitates the development of countermeasures that address a wide variety of injuries. Tissue engineering has emerged as a field with the potential to provide contemporary solutions. In this review, discussions focus on the applications of stem cells in tissue engineering to address health risks frequently faced by combatants at war. Human development depends intimately on stem cells, the mysterious precursor to every kind of cell in the body that, with proper instruction, can grow and differentiate into any new tissue or organ. Recent reports have suggested the greater therapeutic effects of the anti-inflammatory, trophic, paracrine and immune-modulatory functions associated with these cells, which induce them to restore normal healing and tissue regeneration by modulating immune reactions, regulating inflammation, and suppressing fibrosis. Therefore, the use of stem cells holds significant promise for the treatment of many battlefield injuries and their complications. These applications include the treatment of injuries to the skin, sensory organs, nervous system tissues, the musculoskeletal system, circulatory/pulmonary tissues and genitals/testicles and of acute radiation syndrome and the development of novel biosensors. The new research developments in these areas suggest that solutions are being developed to reduce critical consequences of wounds and exposures suffered in warfare. Current military applications of stem cell-based therapies are already saving the lives of soldiers who would have died in previous conflicts. Injuries that would have resulted in deaths previously now result in wounds today; similarly, today's permanent wounds may be reduced to tomorrow's bad memories with further advances in stem cell-based therapies.

In our quest to standardize our formula for a clinical trial, transforming growth factor-beta3 (TGF-β3) alone and in combination with bone morphogenetic protein-6 (BMP-6) were evaluated for their effectiveness in cartilage differentiation. Bone Marrow Stem Cells (BMSCs) and Adipose Derived Stem Cells (ADSCs) were induced to chondrogenic lineage using two different media. Native chondrocytes served as positive control. ADSCs and BMSCs proved multipotency by tri-lineage differentiations. ADSC has significantly higher growth kinetics compare to Chondrocyte only p ≤ 0.05. Using TGF-β3 alone, BMSC revealed higher expressions for hyaline cartilage genes compare to ADSCs. Chondrocyte has significantly higher early chondrogenic markers expression to ADSCs and BMSCs, while BMSCs was only higher to ADSC at chondroadherin, p ≤ 0.0001. On mature chondrogenic markers, chondrocytes were significantly higher to ADSCs and BMSCs for aggrecan, collagen IX, sry (sex determining region y)-box9, collagen II and fibromodullin; and only to ADSC for collagen XI. BMSC was higher to ADSC for aggrecan and collagen IX, p ≤ 0.0001. The combination of TGF-β3 + BMP-6 revealed increased gene expressions on both BMSCs and ADSCs for early and mature chondrogenic markers, but no significance difference. For dedifferentiation markers, ADSC was significantly higher to chondrocyte for collagen I. Glycosaminoglycan evaluations with both formulas revealed that chondrocytes were significantly higher to ADSCs and BMSCs, but none was significant to each other, p ≤ 0.0001. Combination of 10 ng TGF-β3 with 10 ng of BMP-6 enhanced chondrogenic potentials of BMSCs and ADSCs compare to TGF-β3 alone. This could be the ideal cocktail for either cell's chondrogenic induction.

Metallosis is defined as the accumulation and deposition of metallic particles secondary to abnormal wear from prosthetic implants that may be visualized as abnormal macroscopic staining of periprosthetic soft tissues. This phenomenon occurs secondary to the release of metal ions and particles from metal-on-metal hip implants in patients with end-stage osteoarthritis. Ions and particles shed from implants can lead to local inflammation of surrounding tissue and less commonly, very rare systemic manifestations may occur in various organ systems. With the incidence of total hip arthroplasty increasing as well as rates of revisions due to prosthesis failure from previous metal-on-metal implants, metallosis has become an important area of research. Bodily fluids are electrochemically active and react with biomedical implants. Particles, especially cobalt and chromium, are released from implants as they abrade against one another into the surrounding tissues. The body’s normal defense mechanism becomes activated, which can elicit a cascade of events, leading to inflammation of the immediate surrounding tissues and eventually implant failure. In this review, various mechanisms of metallosis are explored. Focus was placed on the atomic and molecular makeup of medical implants, the component/surgical associated factors, cellular responses, wear, tribocorrosion, joint loading, and fluid pressure associated with implantation. Current treatment guidelines for failed implants include revision surgery. An alternative treatment could be chelation therapy, which may drive future studies. Lay Summary Arthroplasty is an invasive procedure which disrupts surrounding joint tissues, and can greatly perturb the joint’s immune homeostasis. In some instances, this may pose a difficult challenge to implant integration. Particles released from implants into the surrounding joint tissues activate the body’s defense mechanism, eliciting a cascade of events, which leads to biotribocorrosion and electrochemical attacks on the implant. This process may lead to the release of even more particles. Besides, implant makeup and designs, frictions between bearing surfaces, corrosion of non-moving parts with modular junctions, surgical mistakes, patient factor, comorbidities, and loosened components can alter the expected function of implants. High accumulations of these ions and particulates result in metallosis, with accompanying adverse complications. Current recommended treatment for failed prosthesis is revision surgeries. However, chelation therapy as a prophylactic intervention may be useful in future efforts but more investigation is required.