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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1941-1948.
Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-05-1601.
Submitted May 19, 2003
Accepted October 17, 2003
Cotransplantation of third-party mesenchymal stromal cells can alleviate one-donor predominance and increase engraftment from double cord transplantation
Dong-Wook Kim, Yang-Jo Chung, Tai-Gyu Kim, Yoo-Li Kim, and Il-Hoan Oh*
Stem Cell Transplantation Center, The Catholic University of Korea, Seoul, Republic of Korea
Cell & Gene Therapy Institute, The Catholic University of Korea, Seoul, Republic of Korea
Department of Microbiology, The Catholic University of Korea, Seoul, Republic of Korea
Department of Cellular Medicine & Biology, The Catholic University of Korea, Seoul, Republic of Korea; Cell & Gene Therapy Institute, The Catholic University of Korea, Seoul, Republic of Korea
* Corresponding author; email: iho{at}catholic.ac.kr.
Although the infusion of umbilical cord blood (UCB) from multiple donors can be a strategy to overcome the cell dose limitation frequently encountered in UCB transplantation, clinical trials have revealed that cells from one donor predominate engraftment. To investigate the origin of and factors influencing this inequality, we performed mixed transplantation of two UCB units with varying degrees of HLA disparities into NOD/SCID mice, and determined the donor origin by PCR-SSOP or RQ-PCR for human STRs. When total mononuclear cells from two units were transplanted as a mixture, cells from one donor predominated (ratio, 81:19), despite comparable overall engraftment when infused as single units, and no augmentation in overall engraftment was observed when compared to the single-unit controls. However, lineage depletion or cotransplantation of mesenchymal stromal cells (MSCs) expanded from third-party bone marrow resulted in more balanced coengraftment. Direct comparison of double UCB transplantation in the presence or absence of MSCs showed that the reduced deviation in the donor ratio (1.8:1 vs. 2.8:1) correlated with a higher overall level of engraftment with MSC cotransplantation. These results indicate that third-party MSCs can be utilized to alleviate donor deviation and facilitate engraftment of multi-donor UCB.
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