Generation of autologous hematopoietic stem cells from induced pluripotent stem cells

Dijkhuis, Liza (2019) Generation of autologous hematopoietic stem cells from induced pluripotent stem cells. Bachelor's Thesis, Biology.

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Abstract

Leukemia is mainly treated with chemotherapy, irradiation and hematopoietic stem cell transplantations (HSCTs). Unfortunately, leukemia can still be fatal, due to relapses and therapy-related mortality. This is partly due to the complications that come along with HSCTs. Allogeneic HSCTs can result in rejection and graft-versus-host disease (GVHD). Moreover, autologous HSCTs can result in relapses, since the collected cells can be contaminated with leukemic cells. Therefore, other forms of HSCTs should be developed to improve leukemia treatment. This could be provoked when induced pluripotent stem cells (iPSCs) could be used as a new source for hematopoietic stem cells (HSCs). In this bachelor thesis, an overview of current findings and challenges in this field has been provided. Studies have investigated multiple ways to generate HSCs from iPSCs. One way to attempt this is through genetic manipulation. Ectopic expression of the HOXB4 gene in iPSCs resulted in generation of HSCs and engraftment in mouse models. Another method is relying on the microenvironment of the iPSCs. Co-injection of iPSCs with stromal cells and hematopoietic cytokines in teratoma-bearing mice is shown to result in HSCs generation in both peripheral blood and bone marrow. A microRNA-based approach was also investigated as a technique to obtain iPSC-derived HSCs. Numerous miRNAs showed stimulation of self-renewal and suppression of differentiation in HSCs. These different techniques for generating iPSCs-derived HSCs hold great potential but still contain some limitations. When these limitations can be overcome, iPSCs can be used as a new source for autologous HSCs and hold great therapeutic potential in leukemia treatment.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Calkhoven, C.F.
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	19 Jul 2019
Last Modified:	23 Jul 2019 08:47
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/20334

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