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    STEM CELL THERABY FOR

    SOME PARASITIC DISEASES

    BY

    ENAS FAKHRYEMAN MAGDY

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    TYPES OF STEM CELLS

    In mammals, there are two broad types of stem

    cells: embryonic stem cells which are isolatedfrom the inner cell mass of blastocysts, and adult

    stem cells , which are found in various tissues.

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    SOURCES OF AUTOLOGOUS ADULT STEM

    CELLS IN HUMANS

    Bone marrow , which requires extraction by harvesting. Adipose tissue (lipid cells), which requires extraction by

    liposuction.

    Blood, which requires extraction through apheresis.

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    PROPERTIES OF STEMCELLS

    Self-renewal : the ability to go through

    numerous cycles of cell division while maintaining

    the undifferentiated state.

    Potency : the capacity to differentiate intospecialized cell types .

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    The patients with parasitic infections, who usually

    belong to the lower socioeconomic strata of our society,

    have limited therapeutic options. Chemotherapy is virtually

    the first choice for the treatment of many parasiticinfections. However, there is a worry about drug resistance

    following long-term, repeated implementation of mass

    drug administration. Stem cell therapy may help these

    patients.

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    STEM CELL THERAPY

    is an interventional treatment that introduces new cells into

    damaged tissues, which help in treating many diseases and injuries.is effective for the treatment of cancers, diabetes mellitus,

    Parkinson's disease, Huntington's disease, cardiovascular diseases,

    neurological disorders, and many other diseases.

    Recently, stem cell therapy has been introduced to treat parasitic

    infections.

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    Mesenchymal stem cells ameliorate S.japonicum inducedliver injury in mice through:

    a. Reducing granuloma egg diameter,

    b. Decreasing serum concentration of TGF-B1 and

    hyaloronic acid;

    c. Inhibiting collagen deposition and expression of collagen

    type 3in infected mice liver tissues.

    SO; prolong the survival time of the infected mice and this

    effect is inhanced by combination with praziquantel.

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    CD(133) human umbilical cord blood stem cells enhance hepatic

    angiogenesis and neovascularization in expermintal animals ,SO,

    enable prolifiration and survival of the damaged cells rather than

    by direct differantiation to hepatocytes.

    By immunohistichemical analysis the newly formed blood vessels

    show +ve expression of human specific angiogenic markers

    CD31,CD34 and von willebrand factors.

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    Transplantation of bone marrow-derived stem

    cells hold a great potential in treating human

    hepatic cirrhosis as they can:

    a. Differentiate into hepatocytes;

    b. Stimulate regeneration of endogenous

    parenchymal cells;

    c. Enhance fibrous matrix degradation.

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    IN MALARIA

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    Scientists from the National Institute for Medical

    Research, UK have identified an atypical progenitor

    cells from malaria-infected mice which can give riseto a lineage of cells capable of fighting this disease,

    and transplantation of these cells into mice with

    severe malaria helps mice recover from the disease.

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    MSCs play an important role in host protective

    immune responses against malaria as they

    increase IL- 12 production

    suppress IL-10 production in recipient animals

    and dramatic reductions of regulatory T cells in

    animals undergoing infusion with these MSCs. .

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    Glycophorin C (CD236R)receptors mediates vivax malaria

    parasite rosetting to normocytes.

    Rosetting assays using CD236R knockdown normocytes

    derived from hematopoietic stem cells further supports the role

    of glycophorin C as a receptor in P vivax rosette formation.

    Blocking of spesific regions of CD236R significantly inhibit

    rosette formation in P.vivax and P.falciparum.

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    In mouse models of Chagas disease, bone marrow

    mono- nuclear cell was found to be effective in:

    a. reducing inflammation and fibrosis induced by

    T. cruzi,

    b. prevented and reversed the right ventricular

    dilatation caused by this protozoon.

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    It has been shown that repeated injections of granulocyte

    colony-stimulating factor (G-CSF), which mobilizes stem

    cells from the bone marrow, decreases inflammation and

    fibrosis in the hearts of chagasic mice. While chagasic mice had 1,702 cardiac genes with

    expression altered by infection, after bone marrow

    mononuclear cell therapy, 96 % of these genes were

    restored to normal levels

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    Small animal positron emission tomography

    (microPET) is used to investigate the migration of

    transplanted MSCs in a murine model of Chagas

    disease, and correlate MSC bio-distribution with

    glucose metabolism and morphology of heart in

    chagasic mice .

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    Cotransplant of stem cells and skeletal myoblasts is

    functionally effective in the Chagas disease ventricular

    dysfunction through: improving ejection fraction (EF); reducing left ventricular end- diastolic volume (LVEDV)

    and left ventricular end-systolic volume (LVESV).

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    In 28 patients with heart failure due to Chagas

    disease; intracoronary injection of bone marrow

    mono- nuclear cells caused significant

    improvements in the New York Heart

    Association (NYHA) class, quality of life

    ;suggesting that it is feasible and it may be

    potentially safe and effective in these patient.

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