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Title: Development of a new method of osteogenesis imperfecta treatment with the use of autologus mesenchymal stem cells transduced with AAV viral vector containing an inactivating cassette for the mutated collagen type I gene


Osteogenesis imperfecta (OI) is a genetically inherited disorder resulting from mutations in genes encoding collagen type I (COL1A1 and COL1A2). The most common symptoms are pronounced bone deformation, low stature. There is not a successful treatment available to date. The major goal of this dissertation was to develop a new treatment option for patients with severe forms of OI consisting of ex vivo genetic correction of autologous MSC derived from adipose tissue (AT-MSC) with an AAV vector containing an inactivating cassette for collagen type I. We established a new protocol for AT-MSC isolation, with liberase 3 as the most effective enzyme. Isolated cells displayed similar characteristics to BM-MSC, in terms of gene expression level, surface antigen profile, except of molecule CD106 present only on BM-MSC and ability to differentiate into osteogenic lineage. We obtained stably transduced AT-MSC over-expressing CXCR4 or GFP marker. We showed, that AT-MSC-CXCR4+ cells displayed higher motility, stronger migration and invasiveness toward SDF-1 gradient, in comparison to control. When tested in vivo, AT-MSC-CXCR4+ engrafted in a higher percentage into bone marrow of NOD/SCID mice, after systemic transplantation. We also constructed an AAV-COL1A1-inactivating vector containing also cDNA for CXCR4 gene and we tested this vector in vitro on AT-MSC. Our study demonstrated that selec ; ted CXCR4+ cells exhibited significantly reduced mRNA level for COL1A1 gene.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

biologia molekularna

Degree grantor:

Wydział Lekarski


Majka, Marcin

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tylko w bibliotece

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Last modified:

Mar 10, 2023

In our library since:

Nov 21, 2012

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ZB-111524 Mar 10, 2023


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