Effects of bone marrow cell transplant on thyroid function in an I131-induced low T4 and elevated TSH rat model

Abstract

Background: We developed a study using low dose radioactive iodine creating an animal model of transient elevation of thyroid stimulating hormone (TSH). Male derived bone marrow cells were transplanted to asses their effect on thyroid function and their capability to repair the thyroid parenchyma.

Results: At 40 an 80 days after I131 treatment, the study groups TSH and T4 serum values both increased and decreased significantly respectively compared to the negative control group. Eight weeks after cell transplantation, neither TSH nor T4 showed a significant difference in any group. The mean number of SRY gene copies found in group I (Left Intracardiac Transplant) was 523.3 and those in group II (Intrathyroid Transplant) were only 73. Group III (No Transplant) and IV had no copies. Group I presented a partial restore of the histological pattern of rat thyroid with approximately 20%-30% of normal-sized follicles. Group II did not show any histological differences compared to group III (Positive control).

Conclusion: Both a significant increase of TSH and decrease of T4 can be induced as early as day 40 after a low dose of I131 in rats. Restore of normal thyroid function can be spontaneously achieved after using a low dose RAI in a rat model. The use of BM derived cells did not affect the re-establishment of thyroid function and might help restore the normal architecture after treatment with RAI.

Figure 1

TSH and T4 concentration on Day 0, 40 and 80 after RAI. TSH and T4 serum levels of study group (n = 15) compared to control group (n = 5). There was statistical difference since day 40 remaining at day 80 when all transplants where done.

Figure 2

TSH and T4 concentrations 8 weeks after transplantation of stem cells. TSH and T4 serum levels of all groups 8 weeks after BM derived cells transplantation. All concentrations of T4 are very similar in all groups with no statistical difference between them. TSH concentration of group II although high compared to other groups had no significant difference. TSH was repeated for group II at 10 weeks after transplantation and the mean was 0.140 μIU/mL.

Figure 3

SRY Amplification using Real Time PCR. A. Amplification curves of all samples. The negative control did not have any amplification. Some DNA samples from group 1 and group 2 were not included in the analysis due to low quality of the DNA extracted. B. Quantitative Analysis Report. Amplification after cycle 41 was taken as background DNA and no copies where reported in the Rotor-Gene 6 software. Ct = Cycle Threshold, Calc Conc = Calculated Concentration, T/T = Total Copies in the Thyroid Gland (Assuming both thyroid lobes were the same size).

Figure 4

Microscopic appearance of rat thyroid after bone marrow cell transplant. A. Group I H + E. 10 weeks after left intra ventricular transplantation. B. Group II H + E. 10 weeks after direct intra thyroid transplantation. C. Group III H+E. (Positive Controls). D. Group IV H + E. (Negative Controls).