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Rochester, MN, United States

Bara J.J.,AO Research Institute Davos | Herrmann M.,AO Research Institute Davos | Evans C.H.,Rehabilitation Medicine Research Center | Miclau T.,San Francisco General Hospital | And 2 more authors.
Journal of Orthopaedic Research | Year: 2016

There is a clear discrepancy between the growth of cell therapy and tissue engineering research in orthopaedics over the last two decades and the number of approved clinical therapies and products available to patients. At the 2015 annual meeting of the Orthopaedic Research Society, a workshop was held to highlight important considerations from the perspectives of an academic scientist, clinical researcher, and industry representative with the aim of helping researchers to successfully translate their ideas into clinical and commercial reality. Survey data acquired from workshop participants indicated an overall positive opinion on the future potential of cell-based therapies to make a significant contribution to orthopaedic medicine. The survey also indicated an agreement on areas requiring improvement in the development of new therapies, specifically; increased support for fundamental research and education and improved transparency of regulatory processes. This perspectives article summarises the content and conclusions of the workshop and puts forward suggestions on how translational success of cell-based therapies in orthopaedics may be achieved. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. Source

Evans C.H.,Rehabilitation Medicine Research Center | Evans C.H.,AO Research Institute Davos
Annals of Biomedical Engineering | Year: 2015

Much effort is expended in developing biomimetic scaffolds that provide the micro-architecture of native tissue with appropriate cellular niches. Such scaffolds are often seeded with progenitor cells to generate engineered replacements for diseased or damaged tissues. An alternative approach relies on biology, rather than technology, to provide scaffolds containing progenitor cells in authentic niches. This article describes the use of accessible living tissues containing endogenous progenitor cells in their native, physiological environments. Such tissues also possess scaffolding properties, and can be readily harvested, manipulated and returned to the patient intra-operatively to facilitate repair and regeneration. Our group has explored the in situ genetic manipulation of cells within these tissues before they are reimplanted, although other means of modulation are certainly possible. Examples of suitable donor tissues include marrow, skeletal muscle and fat. In the case of marrow, clotting produces a moldable, autologous fibrin matrix containing endogenous cells; if necessary, exogenous cells can be added prior to clotting. These approaches have been studied experimentally in orthopaedic contexts, particularly for the healing and regeneration of bone and cartilage. © 2014, Biomedical Engineering Society. Source

Gou S.,Mayo Medical School | Oxentenko S.C.,Mayo Medical School | Eldrige J.S.,Mayo Medical School | Xiao L.,Nanshan Hospital | And 5 more authors.
American Journal of Physical Medicine and Rehabilitation | Year: 2014

Intervertebral disk degeneration has been considered an irreversible process characterized by a decrease in cell viability, attenuation of proteoglycan and type II collagen synthesis, and dehydration of nucleus pulposus. Stem cell therapy specifically addresses the degenerative process and offers a potentially effective treatment modality. Current preclinical studies show that mesenchymal stem cells have the capacity to repair degenerative disks by differentiation toward chondrocyte-like cells, which produce proteoglycans and type II collagen. There has been evidence that mesenchymal stem cell transplantation into the intervertebral disk increases the intradiskal magnetic resonance imaging T2 signal intensity, increases the disk height, and decreases the degenerative grade in animal models. Appropriate selection of cell carriers/matrix is important because it may prevent cell leakage into the spinal canal and provide an environment that facilitates cell proliferation and differentiation. Although human cell therapy trials for degenerative disk disease are on the horizon, potential issues might arise. The authors hereby review the current state of regenerative cell therapy in degenerative disk disease, with emphasis in cell source, techniques for cellular expansion, induction, transplantation, potential benefit, and risks of the use of this novel medical armamentarium in the treatment of degenerative disk disease. Copyright © 2014 by Lippincott Williams & Wilkins. Source

Evans C.H.,Rehabilitation Medicine Research Center | Huard J.,University of Pittsburgh
Nature Reviews Rheumatology | Year: 2015

Injuries to the musculoskeletal system are common, debilitating and expensive. In many cases, healing is imperfect, which leads to chronic impairment. Gene transfer might improve repair and regeneration at sites of injury by enabling the local, sustained and potentially regulated expression of therapeutic gene products; such products include morphogens, growth factors and anti-inflammatory agents. Proteins produced endogenously as a result of gene transfer are nascent molecules that have undergone post-translational modification. In addition, gene transfer offers particular advantages for the delivery of products with an intracellular site of action, such as transcription factors and noncoding RNAs, and proteins that need to be inserted into a cell compartment, such as a membrane. Transgenes can be delivered by viral or nonviral vectors via in vivo or ex vivo protocols using progenitor or differentiated cells. The first gene transfer clinical trials for osteoarthritis and cartilage repair have already been completed. Various bone-healing protocols are at an advanced stage of development, including studies with large animals that could lead to human trials. Other applications in the repair and regeneration of skeletal muscle, intervertebral disc, meniscus, ligament and tendon are in preclinical development. In addition to scientific, medical and safety considerations, clinical translation is constrained by social, financial and logistical issues. © 2015 Macmillan Publishers Limited. All rights reserved. Source

Evans C.,Rehabilitation Medicine Research Center | Evans C.,Collaborative Research Center
International Orthopaedics | Year: 2014

Traditional tissue engineering approaches to the restoration of orthopaedic tissues promise to be expensive and not well suited to treating large numbers of patients. Advances in gene transfer technology offer the prospect of developing expedited techniques in which all manipulations can be performed percutaneously or in a single operation. This rests on the ability of gene delivery to provoke the sustained synthesis of relevant gene products in situ without further intervention. Regulated gene expression is also possible, but its urgency is reduced by our ignorance of exactly what levels and periods of expression are needed for specific gene products. This review describes various strategies by which gene therapy can be used to expedite the repair and regeneration of orthopaedic tissues. Strategies include the direct injection of vectors into sites of injury, the use of genetically modified, allogeneic cell lines and the intra-operative harvest of autologous tissues that are quickly transduced and returned to the body, either intact or following rapid cell isolation. Data obtained from pre-clinical experiments in animal models have provided much encouragement that such approaches may eventually find clinical application in human and veterinary medicine. © 2014 SICOT aisbl. Source

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