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

R.      Aggarwal; J.      Lu; V.      J. Pompili; H.      Das

doi:10.2174/156652412798376125

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.

Keywords: Clinical application, development, expansion, hematopoietic stem cells (HSCs), microenvironment, regulation, multipotent stem cells, transplantation, hematological disorders, immunodeficiency, congenital neutropenia, malignancies, transcriptional factors, signaling cascades, hematopoiesis