title: Ex vivo expansion of hematopoietic stem cells.
abstract: Ex vivo expansion of hematopoietic stem cells (HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing.
authors.affiliation: Taishan Scholar Immunology Program, Binzhou Medical University, Yantai, 264003, China.|Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
authors.forename: JingJing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, 75390, USA. Alec.Zhang@UTSouthwestern.edu.
authors.forename: ChengCheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology; D015316:Genetic Therapy / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D016513:Mice, SCID; D010477:Perfusion; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology
keywords: CRISPR/Cas9; SCID-repopulating cell; cord blood; ex vivo expansion; genome editing; hematopoietic stem cells; niche; signal transduction; transplantation