Stem cells as drug delivery methods: Application of stem cell secretome for regeneration☆

Stem cell imaging: from bench to bedside

Non-viral gene therapy: Gains and challenges of non-invasive administration methods.

Stem cells have emerged as promising tools for the treatment of incurable neural and heart diseases and tissue damage. However, the survival of transplanted stem cells is reported to be low, reducing their therapeutic effects. The major causes of poor survival of stem cells in vivo are linked to anoikis, potential immune rejection, and oxidative damage mediating apoptosis. This review investigates novel methods and potential molecular mechanisms for stem cell preconditioning in vitro to increase their retention after transplantation in damaged tissues. Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to oxidative stress), aggregate formation, and hydrogel encapsulation have been revealed as promising strategies to reduce cell apoptosis in vivo while maintaining biological functions of the cells. Moreover, this review seeks to identify methods of optimizing cell dose preparation to enhance stem cell survival and therapeutic function after transplantation.

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Preconditioning stem cells for in vivo delivery.

Oxygen is essential to cell survival and tissue function. Not surprisingly, ischemia resulting from myocardial infarction induces cell death and tissue necrosis. Attempts to regenerate myocardial tissue with cell based therapies exacerbate the hypoxic stress by further increasing the metabolic burden. In consequence, implanted tissue engineered cardiac tissues suffer from hypoxia-induced cell death. Here, we report on the generation of oxygen-generating hydrogels composed of calcium peroxide (CPO) laden gelatin methacryloyl (GelMA). CPO-GelMA hydrogels released significant amounts of oxygen for over a period of 5 days under hypoxic conditions (1% O2). The released oxygen proved sufficient to relieve the metabolic stress of cardiac side population cells that were encapsulated within CPO-GelMA hydrogels. In particular, incorporation of CPO in GelMA hydrogels strongly enhanced cell viability as compared to GelMA-only hydrogels. Importantly, CPO-based oxygen generation reduced cell death by limiting hypoxia-induced necrosis. The current study demonstrates that CPO based oxygen-generating hydrogels could be used to transiently provide oxygen to cardiac cells under ischemic conditions. Therefore, oxygen generating materials such as CPO-GelMA can improve cell-based therapies aimed at treatment or regeneration of infarcted myocardial tissue.

Oxygen-Generating Photo-Cross-Linkable Hydrogels Support Cardiac Progenitor Cell Survival by Reducing Hypoxia-Induced Necrosis

Feng Lan, Junwei Liu, Kazim H. Narsinh, Shijun Hu, Leng Han, Andrew S. Lee, Marisa Karow, Technique Safe Genetic Modification of Cardiac Stem Cells Using a Site-Specific Integration Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2012 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/CIRCULATIONAHA.111.084913 2012;126:S20-S28 Circulation. http://circ.ahajournals.org/content/126/11_suppl_1/S20 World Wide Web at: The online version of this article, along with updated information and services, is located on the

/pdf/cell-transplantation-and-tissue-regeneration-safe-genetic-1i7w7hn8xp.pdf

Cell Transplantation and Tissue Regeneration Safe Genetic Modification of Cardiac Stem Cells Using a Site-Specific Integration Technique

Background—Although human embryonic stem cells (hESC) have enormous potential for cell replacement therapy of heart failure, immune rejection of hESC derivatives inevitably would occur after transplantation. We therefore aimed to generate a hypoantigeneic hESC line with improved survival characteristics. Methods and Results—Using various in vivo, nonischemic, hindlimb xenotransplant models (immunocompetent and defined immunodefective mouse strains) as well as human in vitro T-cell and natural killer (NK)-cell assays, we revealed a central role for T cells in mediating hESC rejection. The NK-cell susceptibility of hESC in vivo was found to be low, and the NK response to hESC challenge in vitro was negligible. To reduce the antigenicity of hESC, we successfully generated human leukocyte antigen (HLA) I knockdown cells (hESC siRNAIB ) using both HLA I RNA interference (siRNA) and intrabody (IB) technology. HLA I expression was 99% reduced after 7 days and remained low for weeks. Cellular immune recognition of these hESC siRNAIB was strongly reduced in both xenogeneic and allogeneic settings. Immune rejection was profoundly mitigated after hESC siRNAIB transplantation into immunocompetent mice, and even long-term graft survival was achieved in one third of the animals without any immunosuppression. The survival benefit of hESC siRNAIB was further confirmed under ischemic conditions in a left anterior descending coronary artery ligation model. Conclusions—HLA I knockdown hESC siRNAIB provoke T-cell ignorance and experience largely mitigated xenogeneic rejection. By generating hypoantigeneic hESC lines, the generation of acceptable hESC derivatives may become a practical concept and push cell replacement strategies forward. (Circulation. 2011;124[suppl 1]:S3–S9.)

Cell Therapy and Tissue Generation Human Leukocyte Antigen I Knockdown Human Embryonic Stem Cells Induce Host Ignorance and Achieve Prolonged Xenogeneic Survival

Strategic planning is essential for the growth, evolution, and improvement of any successful academic department. This process should be performed with any changes in departmental leadership and at least every 5 years to ensure that the faculty and staff stay engaged and focused on the department’s vision, commonly agreed-upon departmental goals, and the strategies to achieve the vision. The strategic plan should be comprehensive, have clear performance metrics, and should be used as documents for communicating the vision and goals of the department. It is important that the departmental strategic plan serves as a living document and be monitored and evaluated on at least an annual basis for refinement and to address any new trends or changes in the environment.

How to Engage in Departmental Strategic Planning

CHAPTER 7 Comparison of Transplantation of Adipose Tissue- and bone m arrow- Derived m esenchymal s tem Cells in the i nfarcted Heart

L'invention concerne des methodes de production d'une population de cardiomyocytes a partir d'une population de cellules souches pluripotentes de mammifere. Des aspects des methodes incluent l'utilisation d'un agoniste et d'un antagoniste de signalisation Wnt, chacun dans des milieux minimaux, pour moduler la signalisation Wnt. L'invention concerne egalement des necessaires permettant de mettre en pratique lesdites methodes.

Production définie chimiquement de cardiomyocytes à partir de cellules souches pluripotentes

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