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Ali O.A.,Harvard University | Ali O.A.,Wyss Institute for Biologically Inspired Engineering | Ali O.A.,InCytu Inc | Mooney D.J.,Harvard University
Current Topics in Microbiology and Immunology | Year: 2010

Our understanding of immunological regulation has progressed tremendously alongside the development of materials science, and at their intersection emerges the possibility to employ immunologically active biomaterials for cancer immunotherapy. Strong and sustained anticancer, immune responses are required to clear large tumor burdens in patients, but current approaches for immunotherapy are formulated as products for delivery in bolus, which may be indiscriminate and/ or shortlived. Multifunctional biomaterial particles are now being developed to target and sustain antigen and adjuvant delivery to dendritic cells in vivo, and these have the potential to direct and prolong antigen-specific T cell responses. Threedimensional immune cell niches are also being developed to regulate the recruitment, activation and deployment of immune cells in situ to promote potent antitumor responses. Recent studies demonstrate that materials with immune targeting and stimulatory capabilities can enhance the magnitude and duration of immune responses to cancer antigens, and preclinical results utilizing materialbased immunotherapy in tumor models show a strong therapeutic benefit, justifying translation to and future testing in the clinic. © Springer-Verlag Berlin Heidelberg 2011.

Emerich D.F.,InCytu Inc | Orive G.,University of the Basque Country | Orive G.,Biotechnology Institute BTI | Orive G.,CIBER ISCIII | Borlongan C.,University of South Florida
Current Stem Cell Research and Therapy | Year: 2011

Current therapies have limited or no capacity to restore lost function, slow ongoing neurodegeneration, or promote regeneration following damage to the brain. Biomaterials are playing an increasingly important role in the development of novel, potentially efficacious approaches to brain treatment and repair. Programmable biomaterials enable and augment the targeted delivery of drugs into the brain and allow cell/tissue transplants to be effectively delivered and integrate into the brain, to serve as delivery vehicles for therapeutic proteins, and rebuild damaged circuits. Similarly, biomaterials are being increasingly used to recapitulate specific aspects of brain niches to promote regeneration and/or repair damaged neuronal pathways with stem cell therapies. Many of these approaches are gaining momentum because nanotechnology allows greater control over material-cell interactions that induce specific developmental processes and cellular responses including differentiation, migration, and outgrowth. This review discusses the state of the art and new directions in the convergence of biomaterial science, drug delivery, and stem cell biology in the treatment of degenerative and malignant brain diseases. © 2011 Bentham Science Publishers.

Tornoe J.,Nsgene Inc. | Torp M.,Nsgene Inc. | Jorgensen J.R.,Nsgene Inc. | Emerich D.F.,Nsgene Inc. | And 5 more authors.
Restorative Neurology and Neuroscience | Year: 2012

Purpose: Encapsulated cell (EC) biodelivery is a promising, clinically relevant technology platform to safely target the delivery of therapeutic proteins to the central nervous system. The purpose of this study was to evaluate EC biodelivery of the novel neurotrophic factor, Meteorin, to the striatum of rats and to investigate its neuroprotective effects against quinolinic acid (QA)-induced excitotoxicity. Methods: Meteorin-producing ARPE-19 cells were loaded into EC biodelivery devices and implanted into the striatum of rats. Two weeks after implantation, QA was injected into the ipsilateral striatum followed by assessment of neurological performance two and four weeks after QA administration. Results: Implant-delivered Meteorin effectively protected against QA-induced toxicity, as manifested by both near-normal neurological performance and reduction of brain cell death. Morphological analysis of the Meteorin-treated brains showed a markedly reduced striatal lesion size. The EC biodelivery devices produced stable or even increasing levels of Meteorin throughout the study over 6 weeks. Conclusions: Stereotactically implanted EC biodelivery devices releasing Meteorin could offer a feasible strategy in the treatment of neurological diseases with an excitotoxic component such as Huntington's disease. In a broader sense, the EC biodelivery technology is a promising therapeutic protein delivery platform for the treatment of a wide range of diseases of the central nervous system. © 2012 - IOS Press and the authors. All rights reserved.

Huebsch N.,Harvard University | Huebsch N.,Harvard-MIT Division of Health Sciences and Technology | Huebsch N.,Wyss Institute for Biologically Inspired Engineering | Arany P.R.,Harvard University | And 12 more authors.
Nature Materials | Year: 2010

Stem cells sense and respond to the mechanical properties of the extracellular matrix. However, both the extent to which extracellular-matrix mechanics affect stem-cell fate in three-dimensional microenvironments and the underlying biophysical mechanisms are unclear. We demonstrate that the commitment of mesenchymal stem-cell populations changes in response to the rigidity of three-dimensional microenvironments, with osteogenesis occurring predominantly at 11-30 kPa. In contrast to previous two-dimensional work, however, cell fate was not correlated with morphology. Instead, matrix stiffness regulated integrin binding as well as reorganization of adhesion ligands on the nanoscale, both of which were traction dependent and correlated with osteogenic commitment of mesenchymal stem-cell populations. These findings suggest that cells interpret changes in the physical properties of adhesion substrates as changes in adhesion-ligand presentation, and that cells themselves can be harnessed as tools to mechanically process materials into structures that feed back to manipulate their fate. © 2010 Macmillan Publishers Limited. All rights reserved.

Emerich D.F.,InCytu Inc
Advances in Experimental Medicine and Biology | Year: 2010

The choroid plexuses (CPs) play pivotal roles in basic aspects of neural function including maintaining the extracellular milieu of the brain by actively modulating chemical exchange between the CSF and brain parenchyma, surveying the chemical and immunological status of the brain, detoxifying the brain, secreting a nutritive "cocktail" of polypeptides and participating in repair processes following trauma. Even modest changes in the CP can have far reaching effects and changes in the anatomy and physiology of the CP have been linked to several CNS diseases. It is also possible that replacing diseased or transplanting healthy CP might be useful for treating acute and chronic brain diseases. Here we describe the wide-ranging functions of the CP, alterations of these functions in aging and neurodegeneration and recent demonstrations of the therapeutic potential of transplanted microencapsulated CP for neural trauma. © 2010 Landes Bioscience and Springer Science+Business Media.

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