Leiden University Scholarly Publications

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Bogt, K.E.A. van der (2010)

Stem cell therapy for cardiovascular disease : answering basic questions regarding cell behavior

Doctoral Thesis
Stem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the mechanism of action with which the cells could potentially alleviate disease symptoms. The objective of the research as described in this thesis was to visualize survival, proliferation, and migration of embryonic (ESC) and adult stem cells using non-invasive molecular imaging techniques in small animal models of cardiovascular diseases. The major findings can be described as follows: (1) Non-invasive bioluminescence imaging is a validated tool to monitor donor cell survival, proliferation, migration, and misbehavior; (2) ESC are a potential source for true regenerative therapy; (3) ESC form teratomas; (4) Adult stem cell survival is short-lived, but of all cells currently used in the clinic, mononuclear cells show the most prolonged survival; (5) Transplantation of mononuclear cells can preserve...Show moreStem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the mechanism of action with which the cells could potentially alleviate disease symptoms. The objective of the research as described in this thesis was to visualize survival, proliferation, and migration of embryonic (ESC) and adult stem cells using non-invasive molecular imaging techniques in small animal models of cardiovascular diseases. The major findings can be described as follows: (1) Non-invasive bioluminescence imaging is a validated tool to monitor donor cell survival, proliferation, migration, and misbehavior; (2) ESC are a potential source for true regenerative therapy; (3) ESC form teratomas; (4) Adult stem cell survival is short-lived, but of all cells currently used in the clinic, mononuclear cells show the most prolonged survival; (5) Transplantation of mononuclear cells can preserve cardiac function in the short term after myocardial infarction in mice; (6) Compared to other measurements of murine cardiac function, Micro-CT is a superior method to assess cardiac geometry and function; and (7) Transplantation of mononuclear cells in peripheral artery disease is hampered by dismal cell survival and homing. These findings illustrate the current challenges for optimizing stem cell therapy for cardiovascular disease.Show less
Adipose stromal cell
Bioluminescence imaging
Bone marrow stem cell
Cardiovascular disease
Embryonic stem cell
Mesenchymal stem cell
Micro computed tomography
Myocardial infarction
Molecular imaging
Peripheral artery disease
Skeletal myoblast
Stem cell therapy
All authors
Bogt, K.E.A. van der
Supervisor
Hamming, J.F.; Robbins, R.C.
Qualification
Doctor (dr.)
Awarding Institution
Leiden University Medical Center (LUMC), Leiden University
Date
2010-12-16
ISBN (print)
9789070480141

Funding

Sponsorship
Fulbright Foundation, VSB fund, Prof. Michaël-van Vloten Foundation, American Heart Association, Collegium Chirurgicum Neerlandicum, Netherlands Heart Foundation, J.E. Jurriaanse Foundation, ADinstruments, Millar Instruments, Synthes, Triplinq Hosted Solutions, and Servier Nederland Farma B.V.