prikaz prve stranice dokumenta Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells
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doctoral thesis
Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells
Zagreb: University of Zagreb, School of Medicine, 2011. urn:nbn:hr:105:978832
Kuçi, Zyrafete
University of Zagreb
School of Medicine

Cite this document

Kuçi, Z. (2011). Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:978832

Kuçi, Zyrafete. "Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells." Doctoral thesis, University of Zagreb, School of Medicine, 2011. https://urn.nsk.hr/urn:nbn:hr:105:978832

Kuçi, Zyrafete. "Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells." Doctoral thesis, University of Zagreb, School of Medicine, 2011. https://urn.nsk.hr/urn:nbn:hr:105:978832

Kuçi, Z. (2011). 'Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells', Doctoral thesis, University of Zagreb, School of Medicine, accessed 18 April 2024, https://urn.nsk.hr/urn:nbn:hr:105:978832

Kuçi Z. Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2011 [cited 2024 April 18] Available at: https://urn.nsk.hr/urn:nbn:hr:105:978832

Z. Kuçi, "Phenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2011. Available at: https://urn.nsk.hr/urn:nbn:hr:105:978832

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Metadata
TitlePhenotypic and functional characterization of mesenchymal stromal cells generated from human bone marrow CD271+ mononuclear cells
AuthorZyrafete Kuçi
VIAF: 305480932
Mentor Drago Batinić (mentor)
Mentor Peter komentor: Bader (komentor)
Committee membernije dostupno (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2011-12-22, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
OBJECTIVE. In vitro proliferative and differentiation potential of mesenchymal stromal cells (MSCs) generated from CD271+ bone marrow mononuclear cells (CD271-MSCs) has been demonstrated in several earlier and recent reports. In the present study we focused, in addition to proliferative and differentiation potential, on in vitro and in vivo immunosuppressive and lymphohematopoietic engraftment-promoting potential of these mesenchymal stromal cells compared to bone marrow-derived mesenchymal stromal cells generated by plastic adherence (PA-MSCs). MATERIALS AND METHODS. We set up a series of experimental protocols in order to determine the phenotype of bone marrow-derived CD271-MSCs, their clonogenic, proliferative, differentiation and immunosuppressive potential. The potential of CD271-MSCs to improve the engraftment of CD133+ hematopoietic stem cells at co-transplantation was evaluated in immunodeficient NOD/SCID-IL2Rnull mice. RESULTS. In vitro studies demonstrated that CD271-mesenchymal stromal cells differentiate along adipogenic, osteogenic and chondrogenic lineages (trilineage potential), and significantly inhibit the proliferation of allogeneic T-lymphocytes in mixed lymphocyte reaction assays. Elevated levels of prostaglandin E2, but not nitric monoxide, IL-10 or soluble HLA-G, mediated the majority of this immunosuppressive effect. In vivo studies showed that CD271-mesenchymal stromal cells promoted significantly greater lymphoid engraftment than did PA-MSCs when co-transplanted with CD133+ hematopoietic stem cells at a ratio of 8:1 in immunodeficient NOD/SCID-IL2Rnull mice. They induced a 10.4-fold increase in the number of T cells, a 2.5-fold increase in the number of NK cells, and a 3.6-fold increase in the number of B cells, indicating a major qualitative difference between these two mesenchymal stromal cell populations. CONCLUSIONS. Our results indicate that CD271 antigen provides a versatile marker for prospective isolation and expansion of MSCs with immunosuppressive and lymphohematopoietic engraftment-promoting properties. The co-transplantation of such cells together with hematopoietic stem cells in patients with hematologic malignancies may prove valuable in the prevention of impaired/delayed T-cell recovery and graft-versus-host disease.
Abstract (croatian)
SVRHA I CILJ RADA. In vitro proliferacijski i diferencijacijski potencijal mezenhimskih stromalnih stanica podrijetlom od CD271+ mononuklearnih stanica koštane srži (CD271-MSS) pokazan je u nekoliko nedavno objavljenih radova i izvješća. U ovom smo se radu, pored proliferacijskog i diferencijacijskog potencijala tih mezenhimalnih stromalnih stanica fokusirali na njihov in vitro i in vivo imunosupresijski potencijal i potencijal za promociju prihvaćanja limfohematopoetskog presatka u odnosu na mezenhimske stromalne stanica podrijetlom iz koštane srži koje su proizvedene adherencijom na plastiku (PA-MSS). MATERIJAL I METODE. U radu smo postavili niz eksperimentalnih protokola u cilju određivanja fenotipa CD271-MSS podrijetlom iz koštane srži, kao i njihov klonogeni, proliferacijski, diferencijacijski i imunosupresijski potencijal. Potencijal CD271-MSS za promociju prihvaćanja CD133+ krvotvornih matičnih stanica nakon njihove kotransplantacije ispitan je u modelu imunodeficijentnih miševa NOD/SCID-IL2Rγnull. REZULTATI. In vitro pokusi pokazali su da se CD271-mezenhimske stromalne stanice diferenciraju u adipogenu, osteogenu i hondrogenu liniju (trilinijski potencijal) te značajno inhibiraju proliferaciju alogeničnih limfocita T u reakciji pomiješanih limfocita. Glavnina imunosupresijskog učinka posredovana je povećanom razinom prostaglandina E2, a ne dušičnim monoksidom (NO), interleukinom-10 (IL-10) ili topljivim molekulama HLA-G. Pokusi in vivo pokazali su da CD271-mezenhimske stromalne stanice značajno bolje promoviraju prihvaćanje limfoidnih stanica nego li PA-MSS nakon kotransplantacije s CD133+ krvotvornim matičnim stanicama u odnosu 8:1 u imunodeficijentne miševe NOD/SCID-IL2Rγnull. Pri tome CD271-MSS uzrokuju povećanje broja limfocita T za 10,4x, povećanje broja NK-stanica za 2,5x, kao i povećanje broja B-stanica za 3,6x, što ujedno i predstavlja glavnu kvalitativnu razliku između te dvije populacije mezenhimskih stromalnih stanica. ZAKLJUČCI. Naši rezultati pokazuju da antigen CD271 predstavlja pogodan biljeg za prospektivno izdvajanje i ekspanziju mezenhimskih stromalnih stanica koje posjeduju imunosupresijski potencijal i promoviraju prihvaćanje limfohematopoetskog presatka. Kotransplantacija CD271-MSS zajedno s krvotvornim matičnim stanicama u bolesnika s malignim hematološkim bolestima može se pokazati korisnim za sprečavanje poremećaja ili odgođenog oporavka limfocita T, kao i za sprečavanje bolesti zbog reakcije presatka na domaćina (graft-versus-host disease).
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:105:978832
Study programmeTitle: Biomedicine and Health Sciences
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
Type of resourceText
Extent95 str.
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
RepositoryDr Med - University of Zagreb School of Medicine Digital Repository
Created on2023-05-05 07:06:55

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