Establishment of nonmyeloablative allogeneic stem cell transplantation model in H-2 haploidentical mice and its related study.
- Author:
Jian-Jie LI
1
;
Yi ZHANG
;
Ming-Wei ZHANG
;
Chun-Mei HOU
;
Ying WU
;
Ning MAO
;
Hui-Sheng AI
Author Information
1. Department of Hematology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100039, China. Lijj81@hetmail.com
- Publication Type:Journal Article
- MeSH:
Animals;
Female;
Graft vs Host Disease;
prevention & control;
H-2 Antigens;
genetics;
Haplotypes;
Hematopoiesis;
Hematopoietic Stem Cell Transplantation;
mortality;
Male;
Mice;
Mice, Inbred C57BL;
Transplantation Chimera;
Transplantation, Homologous;
Vidarabine;
analogs & derivatives;
pharmacology
- From:
Journal of Experimental Hematology
2004;12(5):655-660
- CountryChina
- Language:Chinese
-
Abstract:
To explore the feasibility of nonmyeloablative conditioning regimens, hematopoietic reconstitution, chimera level and the occurrence of GVHD after nonmyeloablative allogeneic stem cell transplantation in H-2 haploidentical mice, CB6F1 mice were used as the recipient and were divided into 3 groups, mice were pretreated five days before transplantation. Group A was pretreated with myeloablative conditioning regimens (TBI with 10.5 Gy), group B was pretreated by TBI (2 Gy) + Ara-C + Cy and group C-TBI (2 Gy) + Ara-C + CY + Flu, respectively. For all recipient mice, the prevention of GVHD was not given, and 2 x 10(7) bone marrow cells mixed 1 x 10(7) spleen cells from C57BL/6 mice were injected through tail vein on day 0, and then hematopoietic recovery, engraftment and GVHD of recipients were observed. The results of chimera detection after transplantation showed that the engraftment of group A remained full donor chimerism, and engraftments of group B and group C were associated with mixed chimerism or full donor chimerism, but the chimerism of group B remained below 80% and tended to decrease after 50 days whereas chimerism of group C was above 80% (chimerism close to or being full donor type) and preserved even after 50 days. GVHD occurred in all the recipient mice due to that prevention was not given, wherein the occurrence and death rate of GVHD in group A was obviously higher than that of group B and group C (P <0.01), but there was no statistical difference between group B and group C. In conclusion, the nonmyeloablative conditioning regimens mainly based on fludarabine can form stable and lasting engraftment in the body of recipients. The mixed chimerism established in recipients induce tolerance of transplantation and decrease or avoid the occurrence of GVHD.
