Vpliv nemieloablativne presaditve mladih krvotvornih matičnih celic na imunske dejavnike starega prejemnika v mišjem modelu

Justin, Mojca (author), Rožman, Primož (mentor)

Staranje je zapleten, več faktorski proces, ki prizadane celice, tkiva in organe. S staranjem organizma se stara tudi imunski sistem, ki je sicer ključen za obrambo organizma pred škodljivim okoljem. S starostjo povezane okvare imunskega sistema vodijo v nastanek večine s starostjo povezanih bolezni kot so rak, avtoimunske bolezni in srčno-žilne bolezni ter povročijo povečano dovzetnost posameznika za okužbe. Ena izmed možnih terapij, ki bi lahko izboljšala delovanje imunskega sistema v starosti, je presaditev mladih krvotvornih matičnih in progenitorskih celic (KMPC), ki bi jih posamezniku odvzeli in shranili v njegovi mladosti ter ponovno presadili v njegovi starosti. Sklepamo, da bi na ta način mlade in zdrave KMPC po presaditvi »pomladile« stari imunski sistem ter izboljšale njegovo delovanje, ob enem pa bi posamezniku podaljšali njegovo življensko dobo. Omenjeni princip se imunuje heterohrona avtologna presaditev mladih krvotvornih matičnih celic. V raziskavi smo v mišjem modelu uporabili nov način presaditve KMPC s predhodno mobilizacijo endogenih KMC v periferno kri. V ta namen smo uporabili molekulo CASIN, ki začasno izprazni nišo kostnega mozga prejemnika, na ta način pa omogoči večjemu številu presajenih celic pritrjanje vanjo. Z uporabo molekule CASIN smo po presaditvi mladih KMPC starim prejemnicam dosegli visok odstotek donorskega himerizma, dokazali nekatere izboljšave v imunskem sistemu in rahlo povišali mediano preživetja. Kljub temu pa bi bilo za prenos v humano medicino potrebno izvesti dodatne raziskave, ki bi potrdili ugodne učinke tovrstne terapije.

• Language: Slovenian
• Keywords: staranje, presaditev krvotvornih matičnih celic, imunski sistem, staranje imunskega sistema, kostni mozeg, himerizem, CASIN, mišji modeli, dolgoživost
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2021
• PID: 20.500.12556/RUL-132168
• Publication date in RUL: 15.10.2021

JUSTIN, Mojca, 2021, Vpliv nemieloablativne presaditve mladih krvotvornih matičnih celic na imunske dejavnike starega prejemnika v mišjem modelu [online]. Doctoral dissertation. [Accessed 31 May 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=132168

Secondary language

• Language: English
• Title: The effect of non-myeloablative transplantation of young haematopoietic stem cells on immune factors in old receipients in a murine model

Abstract

Aging is a complex multi-factorial process that affects cells, tissues and organs. It also affects the immune system, which is crucial for the body's defense against the harmful environment. Age-related defects of the immune system lead to the development of most age-related diseases, such as cancer, autoimmune and cardiovascular diseases and cause an increased susceptibility to infections. One of the strategies that could improve the function of the immune system of an old individual is the transplantation of young hematopoietic stem and progenitor cells (HSCs) which would be collected from an individual in his/her youth and cryopreserved for a long time. After re-infusion later in life of the same individual, young and healthy HSPCs could »rejuvenate« the old immune system and improve its functioning. Furthermore, individuals lifespan could be prolonged. The process is called heterochronous autologous hematopoietic stem cell transplantation. In this study we used a new method of HSC transplantation with prior mobilization of endogenous HSCs into peripheral blood. For this purpose, we used the molecule CASIN, which temporarily empties the recipient's niche, thus allowing engraftment of a larger number of transplanted cells. With the use of the CASIN molecule, we achieved a high percentage of donor chimerism after transplantation of young HSPCs into old recipients. In the recipients of young HSPCs, we detected some improvements in the function of the immune system and a slighty higher median lifespan. Nevertheless, for translation into human medicine, additional research would be needed to confirm the beneficial effects of this type of therapy.

• Keywords: aging, hematopoietic stem cell transplantation, immune system, immune system aging, bone marrow, chimerism, CASIN, murine models, longevity