Contributor:

Sarnowska, Anna (Promotor) ; Zychowicz, Marzena (Promotor pomocniczy)

Description:

97s.: il., ryc., wykr.; 30 cm.

Degree name:

doktor

Level of degree:

2

Degree discipline :

medical sciences

Degree grantor:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN

Type of object:

Thesis

Location:

Mossakowski Medical Research Institute PAS

Abstract:

The regenerative capacity of tissues and organs is fundamentally dependent on the presence of stem cells (SCs) and their specialized microenvironment, known as the stem cell niche. In the adult human brain, the integrity of the neural stem cell niche - located in the subventricular and subgranular zones is essential for maintaining the neurovascular unit (NVU). However, this integrity is frequently disrupted by ischemic injury or neurodegeneration, which limits the brain's natural ability to recover. Although mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) are not physiologically present in the neural niche, their unique immunomodulatory properties and high secretory activity make them a promising functional equivalent for supporting cells. This study aimed to investigate the mechanisms and interactions within the neural niche in the presence of WJ-MSC and to assess their ability to activate neural stem/progenitor cells (NSC/NPC) while supporting NVU integrity. The research demonstrated that WJ-MSCs are able to survive in various environments; limited nutrient availability does not impair their proliferation, migration, or secretory capacity. In three-dimensional (3D) culture systems, WJ- MSCs were shown to physically interact with endothelial cells (HUVEC), enhancing their survival and stimulating angiogenesis through VEGF-A and VEGF-C signaling pathways. This highlights the important role that physical cell-to-cell interactions play in the organisation of the vascular system. Further analysis revealed that when co-cultured with NSC/NPCs in 3D systems, WJ-MSCs spontaneously organize into spheroid structures that mimic the spatial arrangement of a natural niche. The presence of WJ-MSCs promotes the differentiation of progenitor cells toward a neural phenotype and activates the WJ-MSCs themselves to secrete factors that support neurogenesis and angiogenesis in the long term. These results were verified in an organotypic hippocampal slice model, where WJ-MSCs exhibited significant neuroprotective effects following ischemic injury. The cells demonstrated an adaptive secretory response, producing long-term neuroregenerative and angiogenic factors such as BDNF, GDNF, and angiogenin in response to signals from damaged tissue. Overall, these results confirm that WJ-MSCs can effectively enhance the regenerative capacity of the neural niche, establishing a scientific base for their application in therapeutic approaches to central nervous system injuries and neurodegenerative disorders.

Detailed Resource Type:

PhD Dissertations

Format:

pdf

Resource Identifier:

oai:rcin.org.pl:257757

Source:

IMDiK PAN, ZS 444

Language:

pol

Language of abstract:

eng

Rights:

Creative Commons Attribution BY 4.0 license

Terms of use:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitizing institution:

Mossakowski Medical Research Institute PAS

Original in:

Library of the Mossakowski Medical Research Institute PAS

Access:

Open