KMID : 0366220060410030172
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Korean Journal of Hematology 2006 Volume.41 No. 3 p.172 ~ p.178
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Adenovirus-Mediated Antisense Vector-Induced Inhibition of Human Telomerase RNA May Induce Differentiation of CD34+ Cells
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Kim Seok-Jin
Song Joon-Seok Song Chang-Hee Yoo Ji-Hyun Kim Byung-Soo
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Abstract
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Background: Background Telomerase activation and human telomerase RNA (hTR) expression are known to be related to the preservation of the ¡°stemness¡± of stem cells. In this study, we have inhibited the expression of hTR to find the relationship between the telomerase activity and differentiation of normal hematopoietic stem cells.
Methods: We used cord blood collected from 10 full term pregnant women. We classified the CD34+ hematopoietic stem cells from the same donor into three groups: the Ad-OA group was treated with the recombinant adenoviral (Ad) vector Ad-OA using telomerase antisense, the Ad-M6 group was treated with a mutant version of the Ad-OA without telomerase antisense, and a control group without any treatment.
Results: The mean number of colony-forming cells (CFCs) were 110¡¾38 for the Ad-OA groups, 540¡¾56 for the Ad-M6 groups, and 650¡¾72 for the control groups. Thus, CFCs in the Ad-OA group were lower than in the Ad-M6 group (P£¼0.01). The myeloid portion of the CFCs in the Ad-OA group was higher than the Ad-M6 and control groups (P£¼0.01). The Ad-OA group showed a higher percentage of granulocytes suggesting more of a tendency for myeloid differentiation than the Ad-M6 and control groups (P£¼0.01). We found that the suppression of telomerase activity by the antisense telomerase adenovirus induced the differentiation of hematopoietic stem cells confirmed by differential cell count and cytochemical staining.
Conclusion: These findings suggest that the activity of the telomerase may play a role in the differentiation of normal CD34+ hematopoietic stem cells into mature cells.
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KEYWORD
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Telomerase, Antisense adenovirus, Hematopoietic stem cell, Differentiation
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