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Enhance the feasibility of transplantation of hematopoietic stem / progenitor cell homing and hematopoietic reconstitution ability Strategy

Author: GaoJingZuo
Tutor: ZhengYiZhou
School: Peking Union Medical College , China
Course: Internal Medicine
Keywords: Umbilical cord blood Hematopoietic stem / progenitor cells Bone marrow cavity injection Planting activity Mice , NOD / SCID Homing Hematopoietic reconstitution
CLC: R457.7
Type: Master's thesis
Year: 2008
Downloads: 45
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Abstract

Objective To compare the different sources HS / PC homing ability differences and in-depth explore iBMI technology UCB source HS / PC homing potential, implantation rate, the impact of the hematopoietic and immune reconstitution after transplantation. Methods sources of different number of people the BM mPB and UCB CD34 ~ cells (1 × 10 ~ 3,1 × 10 ~ 4,0.5 × 10 ~ 5,1 × 10 ~ 5,5 × 10 ~ 5), respectively, by the IVI transplanted into and iBMI means by the sub-lethally irradiated NOD / SCID mice. By PCR, tissue sections, flow cytometry and in vivo imaging technique to observe the different sources of CFSE-labeled CD34 - cells in mice timing distribution; On this basis, we focus on comparison UCB-derived CD34 ~ cells The IVI-of UCBT and iBMI-UCBT by the engraftment level in mice dose-dependent, dynamic rate of engraftment of hematopoietic recovery and immune function in vitro clonogenic capacity and secondary reconstruction capabilities. Results (1) different sources HS / PC homing ability to source the difference was not statistically significant (P> 0.05); ② people of different sources of CFSE-labeled CD34 ~ cells in vivo kinetics study shows that the distribution of mice showing obvious chemotactic characteristics, homing early (1h) cells in the the IVI group of mice showed non-specific distribution when 24 hours is focused on the whole body bone parts (especially in the long bones and flat bones), and iBMI group of mouse cell infusion after immediately migrate to the adjacent flat bone can reach other parts of the whole body bone within 24 hours, in the retentate in this process in the liver, lung cells was significantly lower than the IVI group. Until 72 hours after infusion of fluorescent cells in both groups of mice the distribution of basic, mainly concentrated in the the hematopoietic rich flat bone parts. (3) iBMI group by the mice CD34 ~ cell homing efficiency (12 ± 3.91%), approximately 10 times iVI group of people CD34 ~ cell homing efficiency (1.5 ± 0.15%); (4) different number of UCB-CD34 After the ~ cells iBMI transplanted into NOD / SCID mice, 8 weeks engraftment and engraftment levels in a dose-dependent manner. Respectively, by the infusion of the same IVI and iBMI of sources UCB-CD34 to cells 1.0 × 10 5,8 weeks between the two groups of human hematopoietic cell engraftment level (44.063 ± 20.095)% and (45.881 ± 22.316)% difference was not statistically significant (P> 0.05); CD34 ~ cells to 1.0 × 10 4, (54.019 ± 31.338)% significantly by the infusion iBMI human UCB-CD34 ~~ cell engraftment level better than iVI ways (12.197 ± 10.350)%, P <0.01); CD34 ~ cell transfusions to 1.0 × 10 3 the only iBMI infusion of mice to see UCB-CD34 cell engraftment and plant live parts are usually non-infusion site bones. ⑤ UCB-CD34 to cells in mice after long-term engraftment and multi-lineage differentiation, mainly to B and myeloid differentiation after transplantation the five weeks IVI group iBMI of group faculties antigen expression were lower than transplantation 3 weeks and 8 weeks the corresponding values; peripheral blood, spleen and bone marrow of human HS / PC engraftment rate is basically the same trend, after transplantation the eight weeks iBMI group human CD45 - cells IVI group was significantly higher than the corresponding value in the proportion of the site. Conclusion HS / PC homing ability the passive difference between; strategy iBMI transplantation can reduce the detention cells in the liver and lung, so that rapid homing to reach the bone marrow hematopoietic microenvironment, to efficiently enhance its long-term engraftment level, promote hematopoietic reconstruction.

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