Hematopoietic Stem Cells: Transcriptional Regulation, Ex Vivo Expansion and Clinical Application

Overview

Journal Curr Mol Med

Publisher Bentham Science Publishers

Specialty Molecular Biology

Date 2011 Nov 16

PMID 22082480

Citations 32

Authors

R Aggarwal

J Lu

V J Pompili

H Das

Affiliations

Soon will be listed here.

Abstract

Maintenance of ex vivo hematopoietic stem cells (HSC) pool and its differentiated progeny is regulated by complex network of transcriptional factors, cell cycle proteins, extracellular matrix, and their microenvironment through an orchestrated fashion. Strides have been made to understand the mechanisms regulating in vivo quiescence and proliferation of HSCs to develop strategies for ex vivo expansion. Ex vivo expansion of HSCs is important to procure sufficient number of stem cells and as easily available source for HSC transplants for patients suffering from hematological disorders and malignancies. Our lab has established a nanofiber-based ex vivo expansion strategy for HSCs, while preserving their stem cell characteristics. Ex vivo expanded cells were also found biologically functional in various disease models. However, the therapeutic potential of expanded stem cells at clinical level still needs to be verified. This review outlines transcriptional factors that regulate development of HSCs and their commitment, genes that regulate cell cycle status, studies that attempt to develop an effective and efficient protocol for ex vivo expansion of HSCs and application of HSC in various non-malignant and malignant disorders. Overall the goal of the current review is to deliver an understanding of factors that are critical in resolving the challenges that limit the expansion of HSCs in vivo and ex vivo.

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References

Katz B, Zamir E, Bershadsky A, Kam Z, Yamada K, Geiger B . Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol Biol Cell. 2000; 11(3):1047-60. PMC: 14830. DOI: 10.1091/mbc.11.3.1047. View

Zandstra P, Conneally E, Petzer A, Piret J, Eaves C . Cytokine manipulation of primitive human hematopoietic cell self-renewal. Proc Natl Acad Sci U S A. 1997; 94(9):4698-703. PMC: 20787. DOI: 10.1073/pnas.94.9.4698. View

Mehta J, Powles R, Singhal S, Iveson T, Treleaven J, Catovsky D . Clinical and hematologic response of chronic lymphocytic and prolymphocytic leukemia persisting after allogeneic bone marrow transplantation with the onset of acute graft-versus-host disease: possible role of graft-versus-leukemia. Bone Marrow Transplant. 1996; 17(3):371-5. View

Wilson A, Trumpp A . Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol. 2006; 6(2):93-106. DOI: 10.1038/nri1779. View

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

Jordan C, McKearn J, Lemischka I . Cellular and developmental properties of fetal hematopoietic stem cells. Cell. 1990; 61(6):953-63. DOI: 10.1016/0092-8674(90)90061-i. View

Van Ziffle J, Baerlocher G, Lansdorp P . Telomere length in subpopulations of human hematopoietic cells. Stem Cells. 2003; 21(6):654-60. DOI: 10.1634/stemcells.21-6-654. View

Warren A, Colledge W, Carlton M, Evans M, Smith A, Rabbitts T . The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development. Cell. 1994; 78(1):45-57. DOI: 10.1016/0092-8674(94)90571-1. View

North T, Gu T, Stacy T, Wang Q, Howard L, Binder M . Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development. 1999; 126(11):2563-75. DOI: 10.1242/dev.126.11.2563. View

10.

Brugger W, Heimfeld S, Berenson R, Mertelsmann R, Kanz L . Reconstitution of hematopoiesis after high-dose chemotherapy by autologous progenitor cells generated ex vivo. N Engl J Med. 1995; 333(5):283-7. DOI: 10.1056/NEJM199508033330503. View

11.

Siminovitch L, McCulloch E, Till J . THE DISTRIBUTION OF COLONY-FORMING CELLS AMONG SPLEEN COLONIES. J Cell Comp Physiol. 1963; 62:327-36. DOI: 10.1002/jcp.1030620313. View

12.

Lu J, Pompili V, Das H . Hematopoietic stem cells: ex-vivo expansion and therapeutic potential for myocardial ischemia. Stem Cells Cloning. 2013; 3:57-68. PMC: 3781726. DOI: 10.2147/sccaa.s6908. View

13.

McLaughlin F, Ludbrook V, Cox J, von Carlowitz I, Brown S, Randi A . Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation. Blood. 2001; 98(12):3332-9. DOI: 10.1182/blood.v98.12.3332. View

14.

Eichmann A, Corbel C, Nataf V, Vaigot P, Breant C, Le Douarin N . Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor 2. Proc Natl Acad Sci U S A. 1997; 94(10):5141-6. PMC: 24645. DOI: 10.1073/pnas.94.10.5141. View

15.

Bank A, Dorazio R, Leboulch P . A phase I/II clinical trial of beta-globin gene therapy for beta-thalassemia. Ann N Y Acad Sci. 2005; 1054:308-16. DOI: 10.1196/annals.1345.007. View

16.

Ezoe S, Matsumura I, Nakata S, Gale K, Ishihara K, Minegishi N . GATA-2/estrogen receptor chimera regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21(WAF1) and p27(Kip1) proteins. Blood. 2002; 100(10):3512-20. DOI: 10.1182/blood-2002-04-1177. View

17.

Alcorn M, Holyoake T, Richmond L, Pearson C, Farrell E, Kyle B . CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity. J Clin Oncol. 1996; 14(6):1839-47. DOI: 10.1200/JCO.1996.14.6.1839. View

18.

Das H, Abdulhameed N, Joseph M, Sakthivel R, Mao H, Pompili V . Ex vivo nanofiber expansion and genetic modification of human cord blood-derived progenitor/stem cells enhances vasculogenesis. Cell Transplant. 2009; 18(3):305-18. PMC: 2749501. DOI: 10.3727/096368909788534870. View

19.

McBeath R, Pirone D, Nelson C, Bhadriraju K, Chen C . Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004; 6(4):483-95. DOI: 10.1016/s1534-5807(04)00075-9. View

20.

Frickhofen N, Berdel W, Opri F, Haas R, Schneeweiss A, Sandherr M . Phase I/II trial of multicycle high-dose chemotherapy with peripheral blood stem cell support for treatment of advanced ovarian cancer. Bone Marrow Transplant. 2006; 38(7):493-9. DOI: 10.1038/sj.bmt.1705472. View