Identification and characterization of a novel population of murine colonic Sca-1+ cells and implications in Chagas disease.
McPhillips, Megan.
2016
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Abstract: Chagas disease, a chronic degenerative condition caused by the protozoan parasite Trypanosoma cruzi, infects an estimated 10 million people worldwide, mostly in Latin America where it is endemic. The disease has two phases, acute and chronic. Although acute infection is characterized by a high parasite burden in the blood and other tissues, parasitism is kept in check by innate and adapt... read moreive immunity. However, heavy tissue parasitism coupled with a strong immune response elicits tissue destruction, especially in the heart, colon, and esophagus. Nevertheless, most patients progress from acute infection to the chronic phase without permanent tissue damage or sequela, except for less than 5%, who succumb to fulminating myocarditis and encephalomyelitis. Patients acutely infected with T cruzi progress to the chronic indeterminate phase, characterized by extremely low tissue parasitism and absence of symptoms and tissue damage. After many years or decades, about 30% of patients in the indeterminate phase progress to life-threatening pathology in the heart (cardiomegaly) and 10% in the gastrointestinal tract (megaesophagus and megacolon). The time course of Chagas disease progression led us to hypothesize that T cruzi helps the host repair infected tissues by expressing factors such as Parasite Derived Neurotropic Factor (PDNF) that act in concert with endogenous host repair mechanisms. Much attention has been given to the emerging concept that adult stem cells help tissue repair by paracrine signaling, such as through upregulating expression of anti-inflammatory cytokines and growth factors. In support of our hypothesis, recent results in our lab demonstrate that PDNF stimulates self-renewal and survival of reparative Sca-1+ cardiac progenitor/stem cells (CPCs), and enhances secretion of the anti-inflammatory cytokine TSG-6. However, the heart is by no means the sole organ in Chagas disease to suffer severe insult, and given that specific tissue-resident stem cells are being identified throughout the body, it stands to reason that a similar population of progenitor/stem cell exists in the colon with similar reparative properties. My project seeks to isolate a novel population of Sca-1+ cells in the colon of nave mice, characterize the morphology and surface markers, and profile cellular interactions with T cruzi.
At the request of the author, this graduate work is not available to view in the Tufts Digital Library until July 11, 2018.
Thesis (M.S.)--Tufts University, 2016.
Submitted to the Dept. of Immunology.
Advisor: Mercio Perrin.
Committee: Honorine Ward, Pilar Alcaide, and Thereza Imanishi-Kari.
Keyword: Immunology.read less - ID:
- z603r9038
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