Characterization of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development

Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the full value of this emerging field can be realized. The characterization of input material for cell-based therapy bioprocesses from multiple donors is necessary to identify and understand the potential implications of input variation on process development. In this work, we have characterized bone marrow derived human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of the measurable input variation on the development of autologous and allogeneic cell-based therapy manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has been demonstrated that this variation results in a range in the process time between these donor hMSC lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of 29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent of donor variability throughout the expansion process. Measuring informative product attributes during process development will facilitate progress towards consistent manufacturing processes, a critical step in the translation cell-based therapies.

Linking labour force participation, education, labour wages and household consumption in developing countries:push and pull effects in self-employment - evidence from Nigeria

The contribution of this thesis is in understanding the origins in developing countries of differences in labour wage and household consumption vis-à-vis educational abilities (and by extension employment statuses). This thesis adds to the labour market literature in developing countries by investigating the nature of employment and its consequences for labour wage and household consumption in a developing country. It utilizes multinomial probit, blinder-oaxaca, Heckman and quantile regressions to examine one human capital indicator: educational attainment; and two welfare proxies: labour wage and household consumption, in a developing country, Nigeria. It finds that, empirically, the self-employed are a heterogeneous group of individuals made up of a few highly educated individuals, and a significant majority of ‘not so educated’ individuals who mostly earn less than paid workers. It also finds that a significant number of employers enjoy labour wage premiums; and having a higher proportion of employers in the household has a positive relationship with household consumption. The thesis furthermore discovers an upper educational threshold for women employers not found for men. Interestingly, the thesis also finds that there is indeed an ordering of labour wages into low-income self-employment (which seems to be found mainly in “own account” self-employment), medium-income paid employment, and high-income self-employment (which seems to be found mainly among employers), and that this corresponds to a similar ordering of low human capital, medium human capital and high human capital among labour market participants, as expressed through educational attainments. These show that as a whole, employers can largely be classed as experiencing pulled self-employment, as they appear to be advantaged in all three criteria (educational attainments, labour wage and household consumption). A minority of self-employed “own account” workers (specifically those at the upper end of the income distribution who are well educated), can also be classed as experiencing pulled self-employment. The rest of the significant majority of self-employed “own account” workers in this study can be classed as experiencing pushed self-employment in terms of the indicators used.