Targeting The PI۳K/AKT, Wnt/Β-Catenin and Tgfβ Pathways by Small Molecules in Hematopoietic Stem Cell Expansion

سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 138

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شناسه ملی سند علمی:

RROYAN21_018

تاریخ نمایه سازی: 14 فروردین 1401

چکیده مقاله:

Objective: Small molecule compounds have been well recog-nized for their promising power in generation, expansion and maintenance of embryonic or adult stem cells. The aim of this study was to identify a novel combination of small molecules in order to optimize the ex vivo expansion of umbilical cord blood derived-CD۳۴+ cells.Materials and Methods: Considering the most important sign-aling pathways involved in the self-renewal of hematopoietic stem cells, cord blood derived-CD۳۴+ cells were expanded with cytokines in the presence of seven small molecules includ-ing SB, PD, Chir, Bpv, Pur, Pμ and NAM. Eliminativism ap-proach was used to find the best combination of selected small molecules for effective ex vivo expansion of CD۳۴+ cell. In each step, proliferation, self-renewal, and clonogenic potential of the expanded cells as well as expression of some hematopoi-etic stem cell related genes were studied. Finally, the engraft-ment potential of expanded cells was also examined by the mouse intra-uterine transplantation model.Results: Our data shows that simultaneous use of SB۴۳۱۵۴۲ (TGF-β inhibitor), Chir۹۹۰۱ (GSK۳ inhibitor) and Bpv (PTEN inhibitor), resulted in a ۵۰-fold increase in the number of CD۳۴+CD۳۸- cells. This was further reflected in approximately ۳ times increase in clonogenic potential of the small molecule cocktail-expanded cells. These cells, also, showed a ۱.۵-fold higher engraftment potential in the peripheral blood of NMRI model of in utero transplantation. These results are in total conformity with up-regulation of HOXB۴, GATA۲ and CD۳۴ marker gene as well as CXCR۴ homing gene.Conclusion: Taken together, our findings introduce a novel combination of small molecules to improve the yield of exist-ing protocols used in the expansion of hematopoietic stem cells.

نویسندگان

E Afzal

Royan Stem Cell Technology Company, Cord Blood Bank, Tehran

M Zarrabi

Department of Stem Cells and Developmental Biology, Cell Sci-ence Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

MH Asghari

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

M Ebrahimi

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran