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      Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix

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          Abstract

          <p class="first" id="P1">Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen–dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury. The biomaterial can serve as a generic delivery system to improve functional outcomes in cell-replacement therapy. </p>

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          Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens.

          Ex vivo expansion of resident cardiac stem cells, followed by delivery to the heart, may favor regeneration and functional improvement. Percutaneous endomyocardial biopsy specimens grown in primary culture developed multicellular clusters known as cardiospheres, which were plated to yield cardiosphere-derived cells (CDCs). CDCs from human biopsy specimens and from comparable porcine samples were examined in vitro for biophysical and cytochemical evidence of cardiogenic differentiation. In addition, human CDCs were injected into the border zone of acute myocardial infarcts in immunodeficient mice. Biopsy specimens from 69 of 70 patients yielded cardiosphere-forming cells. Cardiospheres and CDCs expressed antigenic characteristics of stem cells at each stage of processing, as well as proteins vital for cardiac contractile and electrical function. Human and porcine CDCs cocultured with neonatal rat ventricular myocytes exhibited biophysical signatures characteristic of myocytes, including calcium transients synchronous with those of neighboring myocytes. Human CDCs injected into the border zone of myocardial infarcts engrafted and migrated into the infarct zone. After 20 days, the percentage of viable myocardium within the infarct zone was greater in the CDC-treated group than in the fibroblast-treated control group; likewise, left ventricular ejection fraction was higher in the CDC-treated group. A method is presented for the isolation of adult human stem cells from endomyocardial biopsy specimens. CDCs are cardiogenic in vitro; they promote cardiac regeneration and improve heart function in a mouse infarct model, which provides motivation for further development for therapeutic applications in patients.
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            Strategies for controlled delivery of growth factors and cells for bone regeneration.

            The controlled delivery of growth factors and cells within biomaterial carriers can enhance and accelerate functional bone formation. The carrier system can be designed with pre-programmed release kinetics to deliver bioactive molecules in a localized, spatiotemporal manner most similar to the natural wound healing process. The carrier can also act as an extracellular matrix-mimicking substrate for promoting osteoprogenitor cellular infiltration and proliferation for integrative tissue repair. This review discusses the role of various regenerative factors involved in bone healing and their appropriate combinations with different delivery systems for augmenting bone regeneration. The general requirements of protein, cell and gene therapy are described, with elaboration on how the selection of materials, configurations and processing affects growth factor and cell delivery and regenerative efficacy in both in vitro and in vivo applications for bone tissue engineering.
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              TGF-β Family Signaling in the Control of Cell Proliferation and Survival

              The transforming growth factor β (TGF-β) family controls many fundamental aspects of cellular behavior. With advances in the molecular details of the TGF-β signaling cascade and its cross talk with other signaling pathways, we now have a more coherent understanding of the cytostatic program induced by TGF-β. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated by TGF-β and determine a cell's proliferation and survival, apoptosis, dormancy, autophagy, and senescence. The difficulty in defining TGF-β's roles partly stems from the context-dependent nature of TGF-β signaling. Here, we review our current understanding and recent progress on the biological effects of TGF-β at the cellular level, with the hope of providing a framework for understanding how cells respond to TGF-β signals in specific contexts, and why disruption of such mechanisms may result in different human diseases including cancer.
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                Author and article information

                Journal
                Nature Biomedical Engineering
                Nat Biomed Eng
                Springer Nature
                2157-846X
                February 2018
                February 6 2018
                : 2
                : 2
                : 104-113
                Article
                10.1038/s41551-018-0191-4
                5927627
                29721363
                ef91a36f-fb7f-450b-a525-6d0273c3b87c
                © 2018

                http://www.springer.com/tdm


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