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Jayanti Tokas1, Rubina Begum1, Shalini Jain2 and Hariom Yadav2

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Presentation on theme: "Jayanti Tokas1, Rubina Begum1, Shalini Jain2 and Hariom Yadav2"— Presentation transcript:

1 Jayanti Tokas1, Rubina Begum1, Shalini Jain2 and Hariom Yadav2
ARTIFICIAL CELLS Life is endowed with a mysterious and divine life-force Jayanti Tokas1, Rubina Begum1, Shalini Jain2 and Hariom Yadav2 1Department of Biotechnology, JMIT, Radaur 2 NIDDK, National Institute of Health, Bethesda,MD20892, USA

2 Artificial Cells Artificial microscopic structures
Same size as biological cells Have some of the functional properties of biological cells. They contain biologically active materials.

3 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

4 Hypothetical cell like structure

5 Membranes Lipid bilayer vesicles(liposomes)-
Multilamellar vesicles(MLVs) Small unilamellar vesicles(SUVs)-5nm-100nm. Large unilamellar vesicles(LUVs)-100nm-1µm. Smallest biological cell µm

6 Transport across cell membranes
An assisted mechanism is necessary Carrier molecules Channels Pumps

7 Channels Neutral peptides Cyclic peptides α-hemolysin
A tetrameric channel - M2 protein

8 Energy Supply ATP molecules from the environment
Mimic the energy transduction process used by all living cells

9 Encapsulating Macromolecules
Catalytic activity of the macromolecule is not damaged Dehydration- re hydration method Freeze- thaw technique Injection of molecules

10 Micro encapsulation To separate functional macromolecules
Regulate exchange of materials Support metabolism Transduce environmental energy into chemical energy Synthesize a desired biosynthetic product

11 Challenges for cell encapsulation
Optimize Biocompatibility Mass transfer Stability Reproducibility Structural Functional relationship Increases Long term stability Repoducible results

12 A number of commercial machines are available for automatic production
of artificial cells

13 Preparation of Artificial cell

14 Two step Method

15 Contd..

16 Contd...

17 Artificial cells Like biological cells, Artificial Cells function with content retained inside to – Act on outside permanent molecules Release products of interaction

18 Dimensions of Polymeric Artificial Cells
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.


20 Artificial cells containing biological cells
Microencapsulated islets for Diabetes Mellitus Microencapsulated hepatocytes for liver failure * Stem cells

21 Artificial cells containing genetically engineered cells
Beta-endorphin secreting cells Recombinant ciliary neurotrophic factor secreting cells Oral therapy for Uremia- E.coli DH 5 cells

22 Artificial cells containing enzymes
Treatment of enzyme deficiency diseases * Phenylketonuria * Lesch Nyan Disease * Skin Cancer Melanoma Urea removal

23 Artificial cells containing microorganisms
Microencapsulation of cholesterol removing microorganisms- Pseudomonas pictorum

24 Artificial Cells With Nano-Dimensions

25 Typical nano-dimension artificial cells
of 80nm mean diameter

26 Artificial RBC(Hb +Enz) with all Biochemical properties

27 Artificial cells in Molecular
Dimensions As Oxygen Carrier

28 Contd..

29 Aid in Cancer Therapy

30 Polymeric Artificial cells Containing
Cell Content Aim Cells and Tissues Pancreatic cells Feedback controlled secretion of insulin for diabetes mellitus Hepatocytes To support liver function in liver failure Kidney cells To secrete erythropoietin to treat anemia Parathyroid Cells To secrete parathyroid hormone to treat hypoparathyroidism

31 Genetically engineered cells
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 hepatocytes Increase duration of viability and function of hepatocytes

32 Microorganisms Pseudomonas pictorum To remove Erwinia herbicola
Contd.. Microorganisms Pseudomonas pictorum To remove Erwinia herbicola To convert ammonia pyruvate and phenol into lysine and DOPA CDH5 E.coli Urea removal Metabolic induction of Lactobacilus delbruecki

33 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.

34 Hemoperfusion Patient’s blood Charcoal-filled artificial cells
Toxins in the blood to enter the cells Adsorbed by the charcoal.

35 Artificial cells as drug delivery vehicles
Drug (biodegradable membrane) fusion Target tissue membrane degraded Drug released

36 Artificial cells as biosensors
analytes signal Coenzyme-depleted enzyme - glucose oxidase

37 Artificial Cell Membrane Holds Promise For Medical Use
Detecting Flue Virus Anti-inflammatory Agent

38 Pink film Tailored Glycolipids(sialic acid) Specific Protein Bind
(Coat proteins of Influenza virus) Pink film

39 Inflammatory Agents Infection/Injury Blood Vessels Produce Receptors
WBC/Neutrophils Bind

40 * Rheumatoid Arthritis * Clamping of Blood Vessels
Contd.. Excess * Rheumatoid Arthritis * Septic Shock * Clamping of Blood Vessels During Surgery

41 Prevents attachment to
Polymerized Membrane Sugars Prevents attachment to Blood Vessels

42 Artificial red blood cells
Modified hemoglobin * high oxygen carrying capacity * do not have blood group antigens * longer half life * non toxic

43 Extracting Hb from RBC’s
RBC’s contain Hb which transport O2 through body RBC’s are lysed with E-Pure water to extract Hb E-Pure Water

44 Modified Hemoglobin I generation II generation III generation

45 Why Cross-link Hb? 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. + Cross-linker In body Cross-linked Hb can no longer travel through pores Hb dimers are small enough to travel through pores

46 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

48 Artificial Human Egg Haploidisation No Cloning
Production of Reconstituted Egg

49 Procedure Woman’s Somatic Cell Shelled Out Oocyte * Problem
*Remove Nucleus *Transfer Shelled Out Oocyte * Problem

50 * Embryo Developed normally in Lab
Artificial Sperm * Dr. Orly Lacham Kalpan succeeded in fertilizing a normal egg with an artificial sperm. * Embryo Developed normally in Lab

51 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.


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