title: Ex-vivo expansion of nonhuman primate CD34+cells by stem cell factor Sall4B.
abstract: Hematopoietic CD34+stem cells are widely used in the clinical therapy of complicated blood diseases. Stem cell factor Sall4B is a zinc finger transcription factor that plays a vital role in hematopoietic stem cell expansion. The purpose of our current study is to further evaluate how Sall4B might affect the expansion of CD34+cells derived from nonhuman primates.
  
  
  
  Sall4B was overexpressed in nonhuman primate bone marrow-derived CD34+cells via a lentiviral transduction system. The granulocyte-erythrocyte-macrophage-megakaryocyte colony-forming unit (CFU) assay evaluated the differentiation potential of primate CD34+cells that were expanded with Sall4B. Furthermore, an in-vivo murine system was employed to evaluate the hematopoietic potential of primate Sall4B-expanded CD34+cells.
  
  
  
  Overexpression of Sall4B promoted ex-vivo nonhuman primate CD34+cell expansion by 9.21 ± 1.94-fold on day 9, whereas lentiviral transduction without Sall4B expanded cells by only 2.95 ± 0.77-fold. Sall4B maintained a significant percentage of CD34+cells as well. The CFU assay showed that the Sall4B-expanded CD34+cells still possessed multilineage differentiation potential. A study using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice in vivo revealed that Sall4B led to an increase in the number of repopulating cells and the 9-day-old Sall4B-transduced CD34+cells still possess self-renewal and multilineage differentiation capacity in vivo, which are similar stemness characteristics to those in freshly isolated primate bone marrow-derived CD34+cells.
  
  
  
  We investigated the expansion of nonhuman primate bone marrow-derived CD34+cells using the Sall4B lentiviral overexpression approach; our findings provide a new perspective on mechanisms of rapid stem cell proliferation. The utilization of Sall4B to expand CD34+cells on a large scale through use of suitable model systems would prove helpful towards preclinical trials of autologous transplantation.
authors.affiliation: Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, 277 Qingqiu Street, Suzhou, 215126, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, 277 Qingqiu Street, Suzhou, 215126, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, 277 Qingqiu Street, Suzhou, 215126, China.|Environmental Medicine, NYU Langone Medical Center, Tuxedo, NY, 10987, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.affiliation: Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, 277 Qingqiu Street, Suzhou, 215126, China. yupoma@yahoo.com.|Department of Pathology, BST-9C, The State University of New York at Stony Brook, Stony Brook, NY, 11794, USA. yupoma@yahoo.com.
authors.forename: Yupo
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, 277 Qingqiu Street, Suzhou, 215126, China. yjiang@biopharmagen.com.|Biopharmagen Corp, Suzhou, 215126, China. yjiang@biopharmagen.com.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D003114:Colony-Forming Units Assay / Q000379:methods; D005260:Female; D057809:HEK293 Cells; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011323:Primates; D019089:Stem Cell Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014182:Transplantation, Autologous / Q000379:methods
chemical_list: D018952:Antigens, CD34; D019089:Stem Cell Factor; D014157:Transcription Factors
keywords: Ex-vivo expansion; NOD/SCID mice; Nonhuman primate CD34+ cell; Sall4B