It’s the start of Open Access Week 2015. To celebrate, and showcase some fantastic content, please find below a list of some of the open access regenerative medicine articles published by Future Science Group so far this year. Featuring articles from Regenerative Medicine, Nanomedicine, Biomarkers in Medicine and Future Science OA, these articles cover topics from specific indications such as spinal cord injuries, Huntington’s disease and Crohn’s disease, wider topics such as discussion of biobanks, regulation and manufacturing challenges, and finally specific techniques, processes and technologies, such as scaffolds and biomarkers. Find summaries and links to the open access articles below!
Hope for regenerative treatments: toward safe transplantation of human pluripotent stem-cell-based therapies.
Kimbrel EA, Lanza R. Regen. Med. 10(2), 99–102 (2015) (doi:10.2217/rme.14.89).
Pluripotent cells such as hESCs and iPSCs have the possibility of being used as cell therapies to treat many diseases, owing to their potential to become any cell type in the body; however, they also come with many risks and challenges. This Editorial discusses topics such as safety considerations, currently approved clinical trials and what is ahead for the use of pluripotent stem cell-based regenerative medicines.
International biobanks: do or do not?
Span PN, Manders P. Future Sci. OA FSO75, doi:10.4155/fso.15.75 (2015). Posted online on 22 Sep 2015.
Biobanks are essential in bench-side and clinical research. However, in order to gather sufficient data, the large-scale investigations required for patient-tailored precision medicine often require multi-institutional or even international human biobanks. This Editorial presents the issues that these biobanks encounter, including definitions, standardization, ethics and regulation.
Treatment of perianal fistulas with human embryonic stem cell-derived MSCs: a canine model of human fistulizing Crohn’s disease.
Ferrer L, Kimbrel EA, Lam A, Falk EB, Zewe C, Juopperi T, Lanza R, Hoffman A. Regen. Med. doi:10.2217/rme.15.69 (2015) (Epub ahead of print). Posted online on 21 Sep 2015.
Crohn’s disease is a chronic inflammatory condition that affects millions of people. Unfortunately, existing treatments are not always effective and patients often become refractory, meaning many patients are in need of a novel, effective therapy. Canine anal furunculosis is a good animal model for this condition as it shares many features with Crohn’s disease, and dogs have a physiology and immune system very similar to humans. This Research Article presents the safety and therapeutic potential of hESC-MSCs in a large animal model of human fistulizing Crohn’s disease for the first time.
Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury.
Priest CA, Manley NC, Denham J, Wirth ED, Lebkowski JS. Regen. Med. doi:10.2217/rme.15.57 (2015) (Epub ahead of print). Posted online on 8 September 2015.
Spinal cord injuries and their secondary effects result in multiple pathologies such as axon severing and demyelination, which in turn can result in symptoms such as paralysis, spasms and pain. Oligodendrocytes are important therapeutic targets following a spinal cord injury as they act as support cells for axons, providing growth factors and myelination support, and are susceptible to cell death following a spinal cord injury. This Research Article aims to characterize the preclinical safety profile of a hESC-derived oligodendrocyte progenitor cell therapy product in rodent models of thoracic spinal cord injuries, in support of its use as a potential treatment for spinal cord injuries and therefore a Phase I trial.
Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.
Hassan S, Simaria AS, Varadaraju H, Gupta S, Warren K, Farid SS. Regen. Med. 10(5), 591–609 (2015) (doi:10.2217/rme.15.29).
Allogeneic stem cells are demonstrating clinical potential for a variety of indications, including graft-versus-host disease and osteoarthritis. However, there are still unresolved issues with scale-up resulting in high manufacturing costs and, as a result, increased interest in more accurate cost estimation modeling. This Research Article aims to develop a decisional tool to identify the most cost-effective process flowsheets for allogeneic cell therapies across a range of production scales in order to assist earlier decision-making during process development.
Cardiopoietic index predicts heart repair fitness of patient-derived stem cells.
Crespo-Diaz R, Yamada S, Bartunek J, Perez-Terzic C, de Waele P, Mauën S, Terzic A, Behfar A. Biomark. Med. 9(7), 639–649 (2015) (doi:10.2217/bmm.15.31).
Despite aggressive medical management, the prognosis of heart failure patients is poor, meaning a new therapy to repair the failing myocardium is needed. Regenerative medicine could help repair the myocardium, but clinical trials have had mixed results. A biomarker-based quality control assay capable of assessing stem cell repair aptitude prior to transplantation is needed to inform clinical use of cell transplants. This Research Article aims to create a biomarker profile capable of predicting the impact of stem cell benefit.
The translation of cell-based therapies: clinical landscape and manufacturing challenges.
Heathman TRJ, Nienow AW, McCall MJ, Coopman K, Kara B, Hewitt CJ. Regen. Med. 10(1), 49–64 (2015) (doi:10.2217/rme.14.73).
Better definition of the manufacturing requirements for cell-based products must be obtained for their use to become widespread in clinics and therefore have a significant impact on healthcare. This Review analyzes 1342 active clinical trials using cell-based therapies to assess the current state of their clinical development and identify gaps in their manufacturing requirements, with the aim of facilitating product translation and future process development.
Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.
Connell JJ, Patrick PS, Yu Y, Lythgoe MF, Kalber TL. Regen. Med. doi:10.2217/rme.15.36 (2015) (Epub ahead of print). Posted online on 21 Sep 2015.
A novel platform technology allowing measurable, controllable and targeted stem cell delivery to the target site would increase efficiency of a cell-based therapy. This Review describes how superparamagnetic iron-oxide nanoparticles can be incorporated into cells for safe and reliable tagging to help guide and measure their delivery.
Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.
Gaut C, Sugaya K. Regen. Med. 10(5), 665–679 (2015) (doi:10.2217/rme.15.31).
Articular cartilage defects often develop into osteoarthritis, a condition that causes the joints to become painful and stiff. It negatively impacts the quality of life of patients and, as it affects millions, has a significant impact on health service costs. Therapeutic approaches to induce stem cell proliferation include modulating local cell signals and utilizing scaffolding techniques – altering the local environment. This Review investigates the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate in order to facilitate optimization of chondrogenesis protocols for regeneration of articular cartilage. It also presents current use of these environmental factors in tissue engineering research.
Developing stem cell therapies for juvenile and adult-onset Huntington’s disease.
Fink KD, Deng P, Torrest A, Stewart H, Pollock K, Gruenloh W, Annett G, Tempkin T, Wheelock V, Nolta JA. Regen. Med. 10(5), 623–646 (2015) (doi:10.2217/rme.15.25).
Stem cell therapies are currently being investigated as potential therapies for several different neurodegenerative conditions. There is a significant focus on MSCs, as they secrete relevant growth factors and help create a neuroprotective microenviroment. Although there are many challenges to developing a clinical product, they have shown clinical benefit and do not have the ethical concerns of ESCs. This Review highlights existing and emerging stem cell therapies for both juvenile and adult-onset Huntington’s disease.
Current practices and reform proposals for the regulation of advanced medicinal products in Canada.
Viswanathan S, Bubela T. Regen. Med. 10(5), 647–663 (2015) (doi:10.2217/rme.15.28).
Stem cells and regenerative medicine are significant areas of interest in Canada, owing to its history of stem cell pioneers as well as strong federal funding, networks and not-for-profits (e.g., CCRM), institutions and industry. This Review presents the regulatory framework for evaluating advanced medicinal products in Canada, and uses the approval of Prochymal™ as a case study demonstraing Canada’s conditional marketing approval system. The article also discusses suggested changes to the regulatory framework and analyzes the overall approach to regulation in Canada.
The likely role of proteolytic enzymes in unwanted differentiation of stem cells in culture.
Penna V, Lipay MVN, Duailibi MT, Duailibi SE. Future Sci. OA FSO75, doi:10.4155/fso.15.26. Posted online on 5 June 2015.
Tissue engineering aims to develop methods for replacing diseased or damaged tissues. Expanding cells in culture is necessary to develop a sufficient number; however, the use of proteolytic enzymes in cell culture can result in unwanted differentiation. This Review looks at the possible mechanisms of cellular change and suggests that the use of proteolytic enzymes needs to be reassessed to ensure clinical safety, presenting possible alternatives that could be used.
A first approach to evaluate the cell dose in highly porous scaffolds by using a nondestructive metabolic method.
Divieto CD, Sassi MP. Future Sci. OA FSO75, doi:10.4155/fso.15.58. Posted online on 7 Sept 2015.
Cell-based therapies require accurate analysis of cell number. This Review presents a new non-invasive methodology for the measurement of 3D proliferation of human mesenchymal stem cells on Biocoral® scaffolds, which may be a valuable tool in cell determination for regenerative medicine and cell–scaffold interaction studies.
Responsive cell–material interfaces.
Dhowre HS, Rajput S, Russell NA, Zelzer M. Nanomedicine 10(5), 849–871 (2015) (doi:10.2217/nnm.14.222).
Accurately recreating the microenvironment of cells with synthetic materials is a significant challenge, as they need to respond to stimuli, be dynamic and so on. Creating materials suitable for biointerfaces is even more difficult. This Review highlights some of the criteria required for responsive, synthetic materials in a biointerface, looks at recent successes in meeting the criteria, and finally suggests the next steps to furthering development, such as including multiple stimuli-responsive surfaces, surfaces of 3D objects and interactive biointerfaces.