Alvarez González, C; (2015) Human umbilical cord stem cells for regenerative neurology: generation of neural-derived progenitors. Doctoral thesis , UCL (University College London).

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Abstract

Human umbilical cord blood (hUCB) has been reported to contain haematopoietic stem cells and a rare “embryonic-like” non-haematopoietic stem cell population. Furthermore, mesenchymal stem cells can be isolated from Wharton’s jelly. These stem cell fractions may provide a valuable cell source for regenerative neurology applications. Thus, the aim of this study was to isolate, characterise, and differentiate umbilical stem cell fractions into neural-derived progenitors. The data suggest that the Lin⁻CD45⁻ “embryonic-like” stem cells present in the cord blood represent a small heterogeneous population phenotypically characterised by the expression of CD34, Nestin, CXCR4 and transcripts typical of pluripotent cells, such as SOX2, OCT3/4, and NANOG. However, they were not able to proliferate in any of the stem cell growth culture media tested and, therefore, defining them as “embryonic-like” stem cell at this stage should be avoided. The results also suggest that the cord blood mononuclear cell fraction (CBMC) expresses neural antigens at basal level but is not able to generate neural progenitors in the xeno-free conditions tested. Finally, the data indicate that the umbilical cord mesenchymal stem cells (UC-MSCs) displayed an important expression of antigens, commonly found in human neural stem cells (hNSCs) but not exclusive, at basal and early differentiation levels. Furthermore, these cells were able to expand in xeno-free conditions containing neural factors known to grow hNSCs. However, although UC-MSCs expressed markers typical of hNSCs, they were unable to differentiate into mature-derived neurons compared to hNSCs. In conclusion, this work suggests that the cord blood haematopoietic and nonhaematopoietic stem cell fractions are unable to generate neural progenitors, and should be avoided for neurotransplant therapy proposes at this stage. Moreover, the UC-MSC fraction appears to be the most plastic cell source in umbilical cord. However, the potential use of UC-MSCs for allogeneic therapy in regenerative neurology applications needs to be further investigated before attempting to translate these cells to the clinical practice.

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