Background— We report that elevated connexin-43 (Cx-43) in stem cells preconditioned with insulin-like growth factor-1 (IGF-1) is cytoprotective and reprograms the cells for cardiomyogenic differentiation. Methods and Results— Sca-1+ cells were preconditioned with 100 nmol/L IGF-1 for 30 minutes followed by 8 hours of oxygen glucose deprivation to assess the cytoprotective effects of preconditioning. LDH release assay, cytochrome c release, and mitochondrial membrane potential assay showed improved survival of preconditioned Sca-1+ cells under oxygen glucose deprivation compared with nonpreconditioned Sca-1+ cells via PI3K/Akt-dependent caspase-3 downregulation. We observed PI3K/Akt-dependent upregulation of cardiac-specific markers including MEF-2c (2.5-fold), GATA4 (3.1-fold), and Cx-43 (3.5-fold). Cx-43 inhibition with specific RNA interference reduced cell survival under oxygen glucose deprivation and after transplantation. In vivo studies were performed in a female rat model of acute myocardial infar...

Sca-1+ stem cell survival and engraftment in the infarcted heart: dual role for preconditioning-induced connexin-43.

Peptides are ubiquitous in nature and useful in many fields, from agriculture as pesticides, in medicine as antibacterial and antifungal drugs founded in the innate immune systems, to medicinal chemistry as hormones. However, the concept of peptides as materials was not recognized until 1990 when a self-assembling peptide as a repeating segment in a yeast protein was serendipitously discovered. Peptide materials are so called because they have bona fide materials property and are made from simple amino acids with well-ordered nanostructures under physiological conditions. These structures include well-ordered nanofibres, nanotubes and nanovesicles. These peptide materials have been used for: (i) three-dimensional tissue cell cultures of primary cells and stem cells, (ii) three-dimensional tissue printing, (iii) sustained releases of small molecules, growth factors, monoclonal antibody and siRNA, (iv) accelerated wound healing in reparative and regenerative medicine as well as tissue engineering, (v) used to stabilize membrane proteins including difficult G-protein coupled receptors and photosystem I for designing nanobiodevices, (vi) a few self-assembling peptides have been used in human clinical trials for accelerated wound healings in surgical uses and (vii) in human clinical trials for siRNA delivery for treatment of cancers. It is likely that these self-assembling peptides will open doors for more and more diverse uses. The field of self-assembling peptides is growing in a number of directions in areas of materials, synthetic biology, and clinical medicine and beyond.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsfs.2017.0028

Discovery and design of self-assembling peptides

Biomedical researchers have become increasingly aware of the limitations of the conventional 2-D tissue cell cultures where most tissue cell studies including cancer and tumor cells have been carried out. They are now searching and testing 3-D cell culture systems, something between a petri dish and a mouse. The important implications of 3-D tissue cell cultures for basic cell biology, tumor biology, high-content drug screening, and regenerative medicine and beyond are far-reaching. How can nanobiotechnology truly advance the traditional cell, tumor, and cancer biology? Why nano is important in biomedical research and medical science? A nanometer is 1000 times smaller than a micrometer, but why it matters in biology? This chapter addresses these questions. It has become more and more apparent that 3-D cell culture offers a more realistic local environment through the nanofiber scaffolds where the functional properties of cells can be observed and manipulated. A new class of designer self-assembling peptide nanofiber scaffolds now provides an ideal alternative system. Time has come to address the 3-D questions because quantitative biology requires in vitro culture systems that more authentically represent the cellular microenvironment in a living organism. In doing so, in vitro experimentation can become truly more predictive of in vivo systems.

Designer self-assembling Peptide nanofiber scaffolds for study of 3-d cell biology and beyond.

Peptide amphiphiles (PAs) are novel engineered biomaterials able to self-assemble into supramolecular systems that have shown significant promise in drug delivery across the cell membane and across challenging biological barriers showing promise in the field of brain diseases, regenerative medicine and cancer. PAs are amino-acid block co-polymers, with a peptide backbone composed usually of 8-30 amino acids, a hydrophilic block formed by polar amino acids, a hydrophobic block which usually entails either non-polar or aromatic amino acids and alkyl, acyl or aryl lipidic tails and in some cases a spacer or a conjugated targeting moiety. Finely tuning the balance between the hydrophilic and hydrophobic blocks results in a range of supramolecular structures that are usually stabilised by hydrophobic, electrostatic, β-sheet hydrogen bonds and π-π stacking interactions. In an aqueous environment, the final size, shape and interfacial curvature of the PA is a result of the complex interplay of all these interactions. Lanreotide is the first PA to be licensed for the treatment of acromegaly and neuroendocrine tumours as a hydrogel administered subcutaneously, while a number of other PAs are undergoing preclinical development. This review discusses PAs architecture fundamentals that govern their self-assembly into supramolecular systems for applications in drug delivery.

/pdf/peptide-self-assemblies-for-drug-delivery-1e49sp9gvu.pdf

Peptide Self-Assemblies for Drug Delivery.

University of Minnesota Ph.D. dissertation. August 2019. Major: Medicinal Chemistry. Advisor: Carston Wagner. 1 computer file (PDF); viii, 275 pages.

Self-assembling Phosphoramidate Pronucleotides: Enzymatic Regulation and Application Towards Therapeutic Delivery

Local Myocardial IGF-1 Delivery with Biotinylated Peptide Nanofibers Improves Cell Therapy for Myocardial Infarction

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Local Myocardial IGF-1 Delivery with Biotinylated Peptide Nanofibers Improves Cell Therapy for Myocardial Infarction