PROTEOME,EKSOSOME,Autologous and Heterologous Cell Therapy


A)What is Proteomics?

 

Proteomics is a rapidly growing field of molecular biology that is concerned with the systematic, high-throughput approach to protein expression analysis of a cell or an organism. Typical results of proteomics studies are inventories of the protein content of differentially expressed proteins across multiple conditions.

The cell responds to internal and external changes by regulating the activity and level of its proteins; therefore changes in the proteome (a collection of all the proteins coded in our genes) provide a snapshot of the cell in action. Proteomics enables the understanding the structure, function and interactions of the entire protein content in a specific organism.

History of proteomics

The term “protein” was initially introduced in 1938 by the Swedish chemist Jöns Jakob Berzelius, an accomplished experimenter in the field of electrochemistry. He wanted to describe a particular class of macromolecules that are plentiful in living organisms and made up of linear chains of amino acids.

The first protein studies that can be called proteomics began in 1975 with the introduction of the two-dimensional gel and mapping of the proteins from the bacterium Escherichia coli, guinea pig and mouse. Albeit many proteins could be separated and visualized, they could not be identified.

The terms “proteome” and “proteomics” were coined in the early 1990s by Marc Wilkins, a student at Australia’s Macquarie University, in order to mirror the terms “genomics” and “genome”, which represent the entire collection of genes in an organism.

Since the first use of the term “proteome”, its meaning and scope have narrowed. Post-translational modifications, alternative splice products, and proteins intractable to classic separation techniques have presented a challenge towards the realization of the conventional definition of the word.

Today, many different areas of study are explored by proteomics. Amongst them are protein-protein interaction studies, protein function, protein modifications, and protein localization studies. The fundamental goal of proteomics is not only to pinpoint all the proteins in a cell, but also to generate a complete three-dimensional map of the cell indicating their exact location.

In many ways, proteomics runs parallel to genomics. The starting point for genomics is a gene in order to make inferences about its products (i.e. proteins), whereas proteomics begins with the functionally modified protein and works back to the gene responsible for its production.

Types of proteomics

Proteomics studies whose goal is to map out the proteins present in a specific cellular organelle or the structure of protein complexes are known as structural proteomics. Structural analysis can aid in identification of the functions of newly discovered genes, show where drugs bind to proteins and where proteins interact with each other. Technologies employed in structural proteomics are X-ray crystallography and nuclear magnetic resonance spectroscopy.

The quantitative study of protein expression between samples that differ by certain variable is known as expression proteomics. This type of proteomics can help identify the main proteins found in a particular sample and proteins differentially expressed in related samples, e.g. when comparing diseased and healthy tissue. Technologies such as 2D-PAGE and mass spectrometry are used here.

Functional proteomics represents a wide-ranging term for many specific, directed proteomics methodologies. The characterization of protein-protein interactions are used to determine protein functions and to demonstrate how proteins assemble in larger complexes. In some cases, specific subproteomes are isolated by affinity chromatography for additional analysis.

Sources

  1. http://www.scipress.com/ILNS.17.77.pdf
  2. http://mmbr.asm.org/content/66/1/39.full
  3. http://www.proteomic-basics.eu/2004/kellner_2.pdf
  4. http://www.plasmaproteome.org/Papers/Vitzthum%20IVD%20Requirements.pdf
  5. Mishra NC. Introduction to Proteomics: Principles and Applications. John Wiley & Sons, 2011; pp. 1-38.
  6. Twyman R. Principles of Proteomics. Garland Science, 2004; pp. 1-22.

By Dr Tomislav Meštrović, MD, PhD

 

B)Exosomes as Reconfigurable Therapeutic Systems

Trends

Exosome diagnostics, although available, remain unapproved by regulatory agencies, and thus might be used in parallel with existing approved tests.

Exosome approaches to therapeutic interventions are far-reaching – from packaging of therapeutic agents to driving immune responses. Applications range from oncology to regenerative medicine, and commercial GMP production at therapeutically relevant quantities is underway.

Exosomes can trigger positive and negative immunomodulatory effects, as observed in early exosome clinical trials for advanced non-small cell lung cancer, thus potentially impacting on disease progression.

The effects of mesenchymal stem cell (MSC) delivery to patients showing therapeutic benefit appear to be exosome-derived because exosomes purified from MSCs can promote similar effects to MSC-based treatments.

The potential for tumor-derived exosomes to control the establishment of organ-specific pre-metastatic niches has been demonstrated through their ability to program bone marrow-derived cells towards a pro-metastatic phenotype.

Historically, small molecules, including steroid hormones and cytokines, have been attributed a role in paracrine and endocrine signaling, and now include a new player: biological nanoparticles, or ‘exosomes’. Generated intracellularly, and defined simply as nanoparticulate packages of signaling moieties, exosomes have emerged as vehicles for highly specialized local and distant intercellular communication. Exosomes are increasingly being recognized as contributing factors in many diseases, and their potential as biomarkers and in therapeutics is rapidly emerging. This review highlights recent advances in the exploitation of exosomes in diagnostic and therapeutic applications. We discuss various facets of nanoparticles, namely the isolation and manipulation of exosomes, the construction of synthetic exosome-like particles in vivo, and their potential use in the treatment of various diseases.

 

R . Steven Conlan'Correspondence information about the author R . Steven Conlan,
Simone Pisano,Marta I. Oliveira,Mauro Ferrari,Inês Mendes Pinto'Correspondence information about the author Inês Mendes Pinto

 

C)Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX.

Ramaswamy S1Tonnu N1Menon T2Lewis BM1Green KT3Wampler D4Monahan PE5Verma IM6.

1Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
2Vertex Pharmaceuticals, 11010 Torreyana Road, San Diego, CA 92121, USA.
3Department of Cellular and Molecular Biology, San Diego State University, Campanile Drive, San Diego, CA 92182, USA.
4Thermo Fisher Scientific, Inc., 5791 Van Allen Way, Carlsbad, CA 92008, USA.
5Shire Therapeutics, 22 Grenville Street, St. Helier, Jersey JE4 8PX, UK.
6Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: verma@salk.edu.

Abstract

Hemophilia B is an ideal target for gene- and cell-based therapies because of its monogenic nature and broad therapeutic index. Here, we demonstrate the use of cell therapy as a potential long-term cure for hemophilia B in our FIX-deficient mouse model. We show that transplanted, cryopreserved, cadaveric human hepatocytes remain functional for more than a year and secrete FIX at therapeutic levels. Hepatocytes from different sources (companies and donors) perform comparably in curing the bleeding defect. We also generated induced pluripotent stem cells (iPSCs) from two hemophilia B patients and corrected the disease-causing mutations in them by two different approaches (mutation specific and universal). These corrected iPSCs were differentiated into hepatocyte-like cells (HLCs) and transplanted into hemophilic mice. We demonstrate these iPSC-HLCs to be viable and functional in mouse models for 9-12 months. This study aims to establish the use of cells from autologous and heterologous sources to treat hemophilia B.

 

SOURCE  https://www.news-medical.net  ,https://www.cell.com ,https://www.ncbi.nlm.nih.gov

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About sooteris kyritsis

Job title: (f)PHELLOW OF SOPHIA Profession: RESEARCHER Company: ANTHROOPISMOS Favorite quote: "ITS TIME FOR KOSMOPOLITANS(=HELLINES) TO FLY IN SPACE." Interested in: Activity Partners, Friends Fashion: Classic Humor: Friendly Places lived: EN THE HIGHLANDS OF KOSMOS THROUGH THE DARKNESS OF AMENTHE
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