Evaluation of hematopoietic stem cell expansion in the presence of garcinol

Document Type : Original Research Article

Authors

1 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Stem Cell and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

3 Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Objective: The application of human cord blood (hCB) is limited to children by using relatively small volume of cord blood that does not contain enough hematopoietic stem cells (HSCs). So, efforts for applying cord blood stem cells in transplantation have led to establishment of some approaches for ex vivo expansion of HSCs such as garcinol.
Materials and Methods: CD133+ HSCs were separated by a magnetic-activated cell sorting (MACS) system. Isolated cells were cultured with different doses of garcinol, SCF, TPO and FLT-3L. The optimal dose of garcinol for ex vivo expansion of HSCs was determined by direct counting. Flow cytometry was used to evaluate the expression of CD133 marker to check the ability of garcinol in maintenance of HSCs. Colony forming cell (CFC) assay was performed to evaluate clonogenic capability of treated cells. The level of expression of CXCR4 gene was evaluated by RT-PCR. Data were analyzed using Student’s t test.
Results: Our results showed that CD133+ HSCs in the presence of garcinol (5-10 µM) had high expansion activity and cell counting showed that the number of cells in treated group was higher than control group (1.9 –fold) and CFC assay showed that the number of colonies following treatment with garcinol had 1.3-fold increase. Treatment of HSCs with garcinol resulted in 9.6-fold increase in terms of CXCR4 expression in comparison to control group.
Conclusion: The present study showed that garcinol can improve ex vivo expansion of HSCs and enhance their potential for homing to bone marrow.

Keywords

Main Subjects

References

Anbarlou A, Atashi A, Soleimani M, AkhavanRahnama M, Bohloli M, Mossahebi-Mohammadi M. 2015. Differential characteristics of CD133+ and CD133− Jurkat cells. In Vitro Cell Dev Biol Anim, 51: 556–561.
Boitano A, Wang J, Romeo R, Bouchez L, Parker A, Sutton S, Denison M. 2010. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science, 329: 1345–1348.
Broxmeyer H, Douglas G, Hangoc G, Cooper S, Bard J, English D, Boyse E. 1989. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci, 86: 3828–3832.
Brunstein C, Barker J, Weisdorf D, Defor T, McKenna D, Chong S, Wagner J. 2009. Intra-BM injection to enhance engraftment after myeloablative umbilical cord blood transplantation with two partially HLA-matched units. Bone Marrow Transplant, 43: 935–940.
Cohen Y, Nagler A. (2004). Umbilical cord blood transplantation–how, when and for whom? Blood Rev, 18: 167–179.
De Lima M, McMannis J, Gee A, Komanduri K, Couriel D, Andersson B, Champlin R. 2008. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant, 41: 771–778.
Ding S, Schultz P. 2004. A role for chemistry in stem cell biology. Nat Biotechnol, 22: 833–840.
Frassoni F, Varaldo R, Gualandi F, Bacigalupo A, Sambuceti G, Sacchi N, Podestà M. 2010. The intra-bone marrow injection of cord blood cells extends the possibility of transplantation to the majority of patients with malignant hematopoietic diseases. Best Pract Res Cl Ha, 23: 237–244.
Gluckman E. 2004. Ex vivo expansion of cord blood cells. Exp Hematol, 32: 410–412.
Holyoake T, Nicolini F, Eaves C. 1999. Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow. Exp Hematol, 27: 1418–1427.
Iwama A, Oguro H, Negishi M, Kato Y, Morita Y, Tsukui H, Koseki H. 2004. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity, 21: 843–851.
Jaroscak J, Goltry K, Smith A, Waters-Pick B, Martin P, Driscoll T, Burhop S. 2003. Augmentation of umbilical cord blood (UCB) transplantation with ex vivo–expanded UCB cells: results of a phase 1 trial using the AastromReplicell System. Blood, 101: 5061–5067.
Kelly S, Sola C, De Lima M, Shpall E. 2009. Ex vivo expansion of cord blood. Bone Marrow Transplant, 44: 673–681.
Ko K, Holmes T, Palladinetti P, Song E, Nordon R, O’Brien T, Dolnikov A. 2011. GSK‐3β Inhibition Promotes Engraftment of Ex Vivo‐Expanded Hematopoietic Stem Cells and Modulates Gene Expression. Stem Cells, 29: 108–118.
Kondo M, Wagers AJ, Manz M, Prohaska S, Scherer D, Beilhack G, Weissman I. 2003. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol, 21: 759–806.
Konuma T, Oguro H, Iwama A. 2010. Role of the polycomb group proteins in hematopoietic stem cells. Dev Growth Differ, 52: 505–516.
Krishnamurthy N, Lewis Y, Ravindranath B. 1981. On the structures of garcinol, isogarcinol and camboginol. Tetrahedron Lett, 22: 793–796.
Mantelingu K, Reddy B, Swaminathan V, Kishore A, Siddappa N, Kumar G, Sadhale P. 2007. Specific inhibition of p300-HAT alters global gene expression and represses HIV replication. Chem Biol, 14: 645–657.
Mayani H, Lansdorp P. 1998. Biology of human umbilical cord blood‐derived hematopoietic stem/progenitor cells. Stem Cells, 16: 153–165.
Mossahebi-Mohammadi M, Atashi A, Kaviani S, Soleimani M. 2017. Efficient expansion of SALL4–transduced umbilical cord blood derived CD133+ hematopoietic stem cells. Acta Med Iran, 55: 290-296.
Nishino T, Miyaji K, Ishiwata N, Arai K, Yui M, Asai Y, Iwama A. 2009. Ex vivo expansion of human hematopoietic stem cells by a small-molecule agonist of c-MPL. Exp Hematol, 37: 1364–1377.
Nishino T, Wang C, Mochizuki-Kashio M, Osawa M, Nakauchi H, Iwama A. 2011. Ex vivo expansion of human hematopoietic stem cells by garcinol, a potent inhibitor of histone acetyltransferase. PLoS ONE, 6: e24298
Nishino T, Osawa M, Iwama A. 2012. New approaches to expand hematopoietic stem and progenitor cells. Expert Opin Biol Ther, 12: 743–756.
Piacibello W, Sanavio F, Garetto L, Severino A, Bergandi D, Ferrario J, Aglietta M. 1997. Extensive amplification and self-renewal of human primitive hematopoietic stem cells from cord blood. Blood, 89: 2644–2653.
Saadat N, Gupta S. 2012. Potential role of garcinol as an anticancer agent. J Oncol, 2012: 1–8.
Sideri A, Neokleous N, De La Grange PB, Guerton B, Kerdilles M, Uzan G, Gluckman E. 2011. An overview of the progress on double umbilical cord blood transplantation. Haematologica, 96: 1213–1220.
TeKippe M, Harrison DE, Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol, 31: 521–527.
Traycoff CM, Abboud MR, Laver J, Clapp DW, Srour EF. 1994. Rapid exit from G0/G1 phases of cell cycle in response to stem cell factor confers on umbilical cord blood CD34+ cells an enhanced ex vivo expansion potential. Exp Hematol, 22: 1264–1272.
Verma IM, Weitzman MD. 2005. Gene therapy: twenty-first century medicine. Annu Rev Biochem, 74: 711–738.
Wang XN, Sviland L, Ademokun AJ, Dunn J, Cavanagh G, Proctor SJ, Dickinson AM. 1998. Cellular Alloreactivity of Human Cord Blood Cells Detected By T-Cell Frequency Analysis and A Human Skin Explant Model1. Transplantation, 66: 903–909.
Avicenna Journal of Phytomedicine
Volume 8, Issue 4
July and August 2018
Pages 350-357

Files

Share

How to cite

Statistics