Thesis Mark van der Garde
On 9 February 2016 Mark van der Garde defended his thesis ‘Different strategies to improve the use of umbilical cord and cord blood for hematopoietic and other regenerative cell therapies’ at the University of Leiden
Promotores: Prof JJ Zwaginga PhD and prof A Brand PhD
The research described in this thesis was conducted at Sanquin Research, Center for Clinical Transfusion Research, Leiden, The Netherlands, and Jon J van Rood Center for Clinical Transfusion Science, Leiden University Medical Center, Leiden, The Netherlands (Dept of Immunohematology and Blood Transfusion and the Experimental Animal Center, LUMC).
The studies were funded by Sanquin, grants PPCOC 06-030 and PPOC 08-009.
Summary
Umbilical cord blood (CB) is an alternative graft source for allogeneic hematopoietic stem cell transplantation (HST). However, CB HST is associated with a poor outcome of transplantation compared to other graft sources, limiting the application of CB. For this thesis we focused on different strategies to improve CB application from both the perspective of the patient (i.e. better engraftment) as well as from the cost perspective (i.e. wider applicability).
Co-transplantation of mesenchymal stem cells (MSC) can improve the outcome of HST. We found that MSC from the Wharton’s Jelly of the umbilical cord (UC) are equally potent in the improvement of engraftment as the MSC from healthy bone marrow donors and the umbilical cord could therefore be a low cost, ethically favorable source for this purpose.
Ex vivo expansion of CB cells with thrombopoietin (TPO) can improve platelet recovery in the peripheral blood. We found that the order of expansion and cryopreservation does not affect engraftment, allowing for already banked products to be used for expansion.
TPO expanded cells are not influenced by co-transplanted cells from another CB the other graft, suggesting that TPO expanded cells can safely be used in a double CB transplantation setting. However, combining TPO expanded cells and MSC does not further improve engraftment and can led to unwanted adverse events and would therefore not be recommended.
Finally, we showed that CB contains non hematopoietic stem cells that can be isolated from the unit without affecting the potential for HST, thereby increasing the possible applications of a single cord blood unit.