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Musculoskeletal injuries that disrupt the structure and function of diarthrodial joints can cause permanent biomechanical alterations and lead to a more severe, chronic condition. Despite advancements that have been made to restore tissue function and delay the need for joint replacement, there are currently no disease-modifying therapies for osteoarthritis (OA). To reduce the risk of OA, innovative preventive medicine approaches have been developed over the last decade to treat the underlying pathology. Several biological approaches are promising treatment modalities for various stages of OA owing to their minimally invasive nature and actively dynamic physiological mechanisms that attenuate tissue degradation and inflammatory responses. Individualized growth factor and cytokine therapies, tissue-engineered biomaterials, and cell-based therapies have revolutionary potential for orthopedic applications; however, the paucity of standardization and categorization of biological components and their counterparts has made it difficult to determine their clinical and biological efficacy. Cell-based therapies and tissue-engineered biologics have become lucrative in sports medicine and orthopedics; nonetheless, there is a continued effort to produce a biological treatment modality tailored to target intra-articular structures that recapitulates tissue function. Advanced development of these biological treatment modalities will potentially optimize tissue healing, regeneration, and joint preservation strategies. Therefore, the purpose of this paper is to review current concepts on several biological treatment approaches for OA. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are being employed in clinical trials to facilitate engraftment and to treat steroid-resistant acute graft-versus-host disease after hematopoietic stem cell transplantation, as well as to repair tissue damage in inflammatory/degenerative disorders, in particular, in inflammatory bowel diseases (IBDs). When entering the clinical arena, a few potential risks of MSC therapy have to be taken into account: (i) immunogenicity of the cells, (ii) biosafety of medium components, (iii) risk of ectopic tissue formation, and (iv) potential in vitro transformation of the cells during expansion. This paper analyzes the main risks connected with the use of MSCs in cellular therapy approaches, and reports on some of the most intriguing findings on the use of MSCs in the context of regenerative medicine. Experimental studies in animal models and phase I/II clinical trials on the use of MSCs for the treatment of IBDs and other inflammatory/degenerative conditions are reviewed. [ABSTRACT FROM AUTHOR]

The 21st century will see improvements in the quality of human life. The development of new therapeutic technologies will prevent prevalent diseases and enable recovery from currently incurable diseases. The development of cell and tissue replacement therapies using stem cells and their progenitors will accelerate the development of causative treatments. The effort expended thus far in developing cell therapies has revealed many technical limitations. Thus, we must explore conceptual changes in the feasibility of stem cell therapy. This paper introduces the current limitations to stem cell engineering and ways to overcome these limitations, which will provide new insight into their clinical application. [ABSTRACT FROM AUTHOR]

Stem cell differentiation, both in vivo and in vitro, is regulated by a variety of signals. These signals can be of biochemical origin, such as those from growth factors and cytokines, or from different mechanical loads, such as fluid shear stress and matrix elasticity. The mechanisms by which the mechanical loads affect precursor cell differentiation are not entirely understood, but their role in regenerative medicine and cell therapy could be of vast importance. This paper reviews the role of mechanical loads on the differentiation of precursor cells. [ABSTRACT FROM AUTHOR]

The induction of hematopoiesis in various cell types via transcription factor (TF) reprogramming has been demonstrated by several strategies. The eventual goal of these approaches is to generate a product for unmet needs in hematopoietic cell transplantation therapies. The most successful strategies hew closely to clues provided from developmental hematopoiesis in terms of factor expression and environmental cues. In this review, we aim to summarize the TFs that play important roles in developmental hematopoiesis primarily and to also touch on adult hematopoiesis. Several aspects of cellular and molecular biology coalesce in this process, with TFs and surrounding cellular signals playing a major role in the overall development of the hematopoietic lineage. We attempt to put these elements into the context of reprogramming and highlight their roles. [ABSTRACT FROM AUTHOR]

Although there has been initial success with some types of immunotherapy, such as adoptive cellular therapy and monoclonal antibody therapy for cancer, the experience with therapeutic cancer vaccines has been much less encouraging. Almost all randomized phase III trials testing therapeutic cancer vaccines have failed to meet their end points. There are several potential explanations for this, ranging from factors related to the clinical trial design and the vaccine itself. Perhaps the most important are host-related factors. Specifically, progression and metastases of many cancers are associated with induction of multiple cancer-specific immune-inhibitory pathways. These inhibitory pathways include induction of T-cell anergy through dendritic cell dysfunction, release of immunosuppressive cytokines, T-cell exhaustion through inhibitory T-cell signaling and T regulatory cell-mediated tumor-specific immune suppression. All of these pathways have been shown to be operational in patients with melanoma. To enhance the activity of therapeutic cancer vaccines, these immunosupressive pathways need to be addressed and reversed. A number of new immunomodulatory reagents that are able to interfere with some of these pathways are now being assessed in the clinic. Sanofi Pasteur designed a clinical trial in patients with advanced or metastatic melanoma that is intended to both induce tumor-specific T-cell responses and modulate or reverse some of the immune suppression pathways that the melanoma has induced. To accomplish this, the recently optimized ALVAC melanoma multi-antigen vaccine is administered with high doses of IFN-α. Clinical trial parameters have also been optimized to enhance the likelihood of inducing and documenting antitumor activity. Success with other therapeutic cancer vaccine approaches will likely require similar approaches in which promising immunogenic vaccines are integrated with biologically and clinically active immunomodulatory reagents. [ABSTRACT FROM AUTHOR]

In this review, we present (1) the scientific basis for the use of high-dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes (T1D); (2) an update of the clinical and laboratory outcome of 20 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, and followed up to January/2008, including 4 relapses among 19 patients without previous ketoacidosis; (3) a commentary on criticisms to our article that appeared in four articles from the scientific literature; and (4) a discussion of the prospectives for cellular therapy for T1D. [ABSTRACT FROM AUTHOR]