[Establishment of nonmyeloablative allogeneic stem cell transplantation model in H-2 haploidentical mice and its related study].
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.
Li
Jian-Jie
JJ
Department of Hematology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100039, China. Lijj81@hetmail.com
Zhang
Yi
Y
Zhang
Ming-Wei
MW
Hou
Chun-Mei
CM
Wu
Ying
Y
Mao
Ning
N
Ai
Hui-Sheng
HS
D000818:Animals; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D006183:H-2 Antigens; D014740:Vidarabine; C024352:fludarabine