Presentation on theme: "ARTIFICIAL CELLS Jayanti Tokas 1, Rubina Begum 1, Shalini Jain 2 and Hariom Yadav 2 1 Department of Biotechnology, JMIT, Radaur 2 NIDDK, National Institute."— Presentation transcript:
ARTIFICIAL CELLS Jayanti Tokas 1, Rubina Begum 1, Shalini Jain 2 and Hariom Yadav 2 1 Department of Biotechnology, JMIT, Radaur 2 NIDDK, National Institute of Health, Bethesda,MD20892, USA Life is endowed with a mysterious and divine life-force
Artificial Cells Artificial microscopic structures Same size as biological cells Have some of the functional properties of biological cells. They contain biologically active materials.
Properties of an ideal minimal cell An information carrying polymer Transport across the membrane An external source of chemical energy A catalytic activity Growth and Division Regulation
Transport across cell membranes An assisted mechanism is necessary Carrier molecules Channels Pumps
Channels Neutral peptides Cyclic peptides α-hemolysin A tetrameric channel - M 2 protein
Energy Supply ATP molecules from the environment Mimic the energy transduction process used by all living cells
Encapsulating Macromolecules Catalytic activity of the macromolecule is not damaged Dehydration- re hydration method Freeze- thaw technique Injection of molecules
Micro encapsulation To separate functional macromolecules Regulate exchange of materials Support metabolism Transduce environmental energy into chemical energy Synthesize a desired biosynthetic product
Challenges for cell encapsulation Optimize Biocompatibility Mass transfer Stability Reproducibility Structural Functional relationship Increases Long term stability Repoducible results
A number of commercial machines are available for automatic production of artificial cells
Preparation of Artificial cell
Two step Method
Artificial cells Like biological cells, Artificial Cells function with content retained inside to – Act on outside permanent molecules Release products of interaction
Macro dimensions For genetically engineered cells, stem cells, other cells, tissues, microorganisms, etc. Micron dimensions For enzymes, genetically engineered microorganisms and other microorganisms, peptides, etc. Nano dimensions For blood substitutes, enzymes, peptides, magnetic materials, drugs, etc. Molecular dimensions For blood substitutes, crosslinked enzymes, conjugated proteins, etc. Dimensions of Polymeric Artificial Cells
Typical nano-dimension artificial cells of 80nm mean diameter
Artificial RBC(Hb +Enz) with all Biochemical properties
Artificial cells in Molecular Dimensions As Oxygen Carrier
Aid in Cancer Therapy
Polymeric Artificial cells Containing Cells Cell ContentAim Cells and Tissues Pancreatic cellsFeedback controlled secretion of insulin for diabetes mellitus HepatocytesTo support liver function in liver failure Kidney cellsTo secrete erythropoietin to treat anemia Parathyroid CellsTo secrete parathyroid hormone to treat hypoparathyroidism
Contd.. Genetically engineered cells Mouse myoblast (mGH gene) SK2 hybridoma cells Secrete mGH for dwarfism Secrete anti-hIL-6 monoclonal Abs for IgG1 plasmacytosis Mouse myoblasts (human factor IX geen) Secrete human factor IX for hemophilia B Hamster kidney cells (CNTF gene)Secrete ciliary neutrotrophic factor for amytrophic lateral sclerosis Neuro2A cells (pro-piomelaocortin gene) Secrete β-endorphin for pain treatment Stem cells Stem cells plus hepatocytesIncrease duration of viability and function of hepatocytes
Contd.. Microorganisms Pseudomonas pictorum To remove Erwinia herbicolaTo convert ammonia pyruvate and phenol into lysine and DOPA CDH5 E.coliUrea removal Metabolic induction of Lactobacilus delbruecki Urea removal
Bioactive sorbants Activated charcoal and resins Ultra thin coating of colloidal membrane Detoxify the blood – hemoperfusion. McGill Artificial Cells and Organ Research Centre in the late 1960s.
Hemoperfusion Patient’s blood Charcoal-filled artificial cells Toxins in the blood to enter the cells Adsorbed by the charcoal.
Artificial cells as drug delivery vehicles Drug (biodegradable membrane) fusion Target tissue membrane degraded Drug released
Artificial cells as biosensors Artificial cells analytes signal Coenzyme-depleted enzyme - glucose oxidase
Artificial Cell Membrane Holds Promise For Medical Use Detecting Flue Virus Anti-inflammatory Agent
Tailored Glycolipids (sialic acid) Specific Protein (Coat proteins of Influenza virus) Pink film Bind
Infection/Injury Blood Vessels Produce Receptors WBC/Neutrophils Bind Inflammatory Agents
Excess * Rheumatoid Arthritis * Septic Shock * Clamping of Blood Vessels During Surgery Contd..
Polymerized Membrane Prevents attachment to Blood Vessels Sugars
Artificial red blood cells Modified hemoglobin * high oxygen carrying capacity * do not have blood group antigens * longer half life * non toxic
Extracting Hb from RBC’s RBC’s contain Hb which transport O 2 through body RBC’s are lysed with E-Pure water to extract Hb E-Pure Water
Modified Hemoglobin I generation II generation III generation
Why Cross-link Hb? + Cross-linker In body Hemoglobin must be cross-linked when placed in the blood stream. – Hb breaks into dimers which can travel through capillary pores (holes) and cause death. Hb dimers are small enough to travel through pores Cross-linked Hb can no longer travel through pores
Present status Hemoperfusion for acute poisoning (clinical trials) Hemoperfusion for aluminium and iron overload (clinical trials) Red blood cell substitute (clinical trials) Diabetes mellitus animal experiments (clinical trials) Drug delivery systems Artificial liver support (experimental) Hereditary enzyme deficiency (clinical trials)
NASA supported Researches for dehydrated blood Supplies Artificial Sperm Artificial Human Eggs Possible In 5 years
Artificial Human Egg Haploidisation No Cloning Production of Reconstituted Egg
Procedure Woman’s Somatic Cell Shelled Out Oocyte *Remove Nucleus *Transfer * Problem
Artificial Sperm * Dr. Orly Lacham Kalpan succeeded in fertilizing a normal egg with an artificial sperm. * Embryo Developed normally in Lab
Conclusion Artificial cells allow to combine properties of biological systems for therapeutic and diagnostic applications. Artificial cell is an attempt to mimic some of the biological processes of a real cell, it may ultimately prove most useful as a partial substitute for animal cells.