doktorska disertacija
Katerina Jazbec (Author), Primož Rožman (Mentor), Marko Kreft (Thesis defence commission member), Mojca Narat (Thesis defence commission member), Gregor Majdič (Thesis defence commission member), Toni Petan (Thesis defence commission member), Urban Švajger (Co-mentor)

Abstract

Starostne spremembe imunskega sistema so vzrok za zmanjšano sposobnost obrambe proti okužbam, za pojav vnetnih bolezni in povečano incidenco raka. Obstaja več teorij, ki skušajo razložiti številne istočasne in prepletene procese staranja. Po teoriji staranja matičnih celic je za staranje tkiv in organov odgovoren upad sposobnosti matičnih celic, da bi uspešno obnavljale tkiva. Namen naše raziskave je bil na modelu laboratorijskih miši raziskati, ali lahko presaditev celic kostnega mozga (KM) mladih živali izboljša delovanje imunskega sistema starih živali ter s tem izboljša njihovo splošno zdravje in morda celo podaljša življenjsko dobo. Neobsevanim samicam BALB/c smo v 14., 16. in 18. (19.) mesecu starosti presadili celice KM mladih samcev. Vsem prejemnicam celic KM smo določili stopnjo himerizma v KM, v izoliranih populacijah limfocitov T, limfocitov B in nevtrofilcev ter v CFU kolonijah, pripravljenih iz KM prejemnic. Analizirali smo spremembe števila celic prirojenega in pridobljenega imunskega sistema ter funkcij imunskih celic po presaditvi (sposobnost endocitoze, citokinski odziv in test stimulacije proliferacije). Manjše število živali smo imunizirali s hemocianinom iz školjke (KLH) ter z analizo titra protiteles testirali njihov imunski odziv na antigen. Pri vseh miših smo redno ocenjevali 30 različnih parametrov ter določili indeks krhkosti. Spremljali smo njihovo življenjsko dobo ter ob smrti opravili raztelesbe ter beležili patoanatomske spremembe. Rezultati so pokazali, da so imele stare miši, ki so prejele celice mladega KM, izboljšane nekatere imunske parametre prirojenega in pridobljenega imunskega sistema v primerjavi s kontrolno skupino, vendar teh ni bilo dovolj, da bi lahko hipotezo raziskave potrdili. Prejemnice KM niso imele vidno boljšega splošnega zdravja, indeks krhkosti ni pokazal razlik med poskusno in kontrolno skupino in miši tudi niso živele dlje od kontrolne skupine miši.

Keywords

staranje;presaditev kostnega mozga;krvotvorne matične celice;miši;imunski sistem;himerizem;indeks krhkosti;dolgoživost;doktorske disertacije;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UL BF - Biotechnical Faculty
Publisher: [K. Jazbec]
UDC: 6:616.419:612,017(043.3)
COBISS: 84466691 Link will open in a new window
Views: 326
Downloads: 39
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Other data

Secondary language: English
Secondary title: ǂThe ǂimmune system and lifespan of BALB/c mice after transplantation of bone marrow cells from young donors
Secondary abstract: Age-related changes in immune functions are the cause of the increased vulnerability to infections, inflammatory diseases, and cancer incidence. There are many existing theories that try to explain the numerous, simultaneous, and interconnected aging processes. The stem cell theory of aging postulates that stem cells become inefficient at maintaining the original functions of the tissues. In our study, we used a mice model to observe whether non-conditioned bone marrow (BM) cell transplantation from young donors to old recipients would improve their immune system functions, improve their general health, and possibly even extend their lifespans. Female BALB/c mice received BM cells from young donors at 14, 16 and 18(19) months of age. We determined chimerism levels in the BM, isolated T cell, B cell and neutrophil populations, and in colony-forming units (CFU) in BM. We analysed the changes of relative cell number of the innate and adaptive immune systems, and conducted functional assays (endocytic capability, cytokine response, and cell proliferation). We immunized a small group of mice with keyhole limpet haemocyanin (KLH) antigen and tested their immune response to antigen. All mice were regularly assessed using 30 parameters to calculate a frailty index (FI). We noted their lifespans, conducted post-mortem examinations, and recorded any pathoanatomical changes. Our results showed that old mice, transplanted with the BM cells of young donors, had some improvement in the immune parameters of their innate and adaptive systems, however, the evidence was insufficient for us to confirm our hypothesis. Recipient mice did not experience a noticeable improvement in their general health, and the FI showed no significant differences between the transplanted and control mice. In addition, the transplanted group did not live longer than the control group.
Secondary keywords: aging;bone marrow transplantation;hematopoietic stem cells;mice;cell isolation;fraility index;longevity;
Type (COBISS): Doctoral dissertation
Study programme: 0
Thesis comment: Univ. v Ljubljani, Biotehniška fak.
Pages: XV f., 164, [32] str.
ID: 13870669