After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications

Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity.

/pdf/molecular-imaging-of-stem-cells-tracking-survival-3q3xc71bwa.pdf

Molecular imaging of stem cells: tracking survival, biodistribution, tumorigenicity, and immunogenicity.

There are several strategies for cell delivery in cardiac stem cell therapy. The cells can be delivered through coronary arteries, coronary veins, or peripheral veins. Alternatively, direct intramyocardial injection can be performed, using a surgical, transendocardial, or transvenous approach. In this article, we describe the most important conceptual aspects and the evidence for the use of these techniques, with emphasis on intramyocardial injections.

Methods of stem cell delivery in cardiac diseases

279 Objectives The objective of this study was to develop a fast and reproducible fully automated method for the production of agents for image guided alpha-therapy (TAT) using miniAIO synthesis module (SmartMedix TM) made by Trasis SA. The Pb203/Pb212 is a matched pair of isotopes that can be applied for SPECT imaging [Pb203] and radiotherapy [Pb212]. Our goal was to develop and validate protocols for the automated pre-purification of Pb203, and labeling and formulation of Pb203-agents. Methods Pb203-SPECT agent automated radiosynthesis is performed either through direct Pb203-labeling of the peptide precursor or, through labeling of the peptide precursor with purified Pb203. In the latter case, the automated process includes a pre-purification/pre-concentration step of the Pb203 isotope (Lantheus Medical Imaging; NCI/NIH-Bethesda). Both approaches have been first validated in manual labeling and their efficacy was compared to the yield (RCY%) of reactions done by automated modules. The pre-concentration of Pb203 is performed using cartridge-based method described previously. [1] Briefly, Eichom Pb203 resin (30mg) is loaded with Pb203 dissolved in 0.5N nitric acid, and subsequently washed out with 2ml of 0.5M nitric acid to remove metallic impurities. The purified Pb203 is eluted using 1 ml of 0.4N ammonium acetate buffer directly to the reaction vial containing the peptide (octreotide derivative) dissolved in 1ml acetate buffer. Labeling occurs at 95°C for 10 min and is followed by direct formulation of the final product. Alternatively, the Pb203 is transferred directly to the reaction vial. The quality control of the product included its radiochemical/radionuclide characterization, pH determination, endotoxin and osmolality tests. Results RCY~ 100% was achieved for reactions of 281-595 MBq of Pb203 and 10µg of peptide. The automated process is completed within 20min (including pre-concentration and formulation step) on the miniAIO® Trasis module while the manual approach requires >35min. The labeled Pb203-peptide remains stable up to 72h post-labeling. A single manifold based cassette allows for direct labeling of Pb203 while a dual manifold based cassette system is required for the process including a pre-concentration and/or purification of the final product. There is no need for C18 post-purification of the tested product although this step was implemented for other (glycol)peptide agents. Conclusions We have developed a protocol for radiosynthesis of Pb203-peptide using the Trasis miniAIO® module (SmartMedix TM). The automation allows for consistent and reliable production of high activity doses, by increasing the efficacy of pre-concentration step, reduction of the time of synthesis and minimizing the user exposure to radiation. This process will be further validated for centralized production of Pb203-probes used in clinical studies.

https://jnm.snmjournals.org/content/jnumed/57/2/279.full.pdf

Dynamic In Vivo SPECT Imaging of Neural Stem Cells Functionalized with Radiolabeled Nanoparticles for Tracking of Glioblastoma

Background Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium. Methods Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to quantify interleukin-8 (IL-8), vascular endothelial growth factor, matrix metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model. Immunohistological analysis was performed to detect inflammatory and pro-angiogenic cells within 72 h post-infarction. Functional data and determination of infarction size were quantified by echocardiography and Elastica van Gieson staining. Results The IA-PBMC attenuated immune reactivity and resulted in secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial progenitor cells within 72 h as compared to control (medium alone, viable-PBMC). Echocardiography showed a significant reduction in infarction size and improvement in post AMI remodelling as evidenced by an attenuated loss of ejection fraction. Conclusion These data indicate that infusion of IA-PBMC cell suspension in experimental AMI circumvented inflammation, caused preferential homing of regenerative EPC and replaced infarcted myocardium.

Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardium.

Bone marrow stem cell imaging after intracoronary administration.

266 The POZNAN Trial ‐ percutaneous transvenous transplantation of autologous myoblasts in the treatment of postinfarction heart failure. One year follow‐up

412 Percutaneous transvenous transplantation of autologous myoblasts in the treatment of postinfarction heart failure two years follow‐up of the POZNAN trial

260 Extravasation of intracoronary administered bone‐marrow derived CD34+ stem cells in patients with acute myocardial infarction evidenced by In 111 cell labelling

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

M. Majewski

Author Tools

Chat about Author

Papers

Bone marrow stem cell imaging after intracoronary administration.

266 The POZNAN Trial ‐ percutaneous transvenous transplantation of autologous myoblasts in the treatment of postinfarction heart failure. One year follow‐up

412 Percutaneous transvenous transplantation of autologous myoblasts in the treatment of postinfarction heart failure two years follow‐up of the POZNAN trial

260 Extravasation of intracoronary administered bone‐marrow derived CD34+ stem cells in patients with acute myocardial infarction evidenced by In 111 cell labelling