title: Cellular-based therapies to prevent or reduce thrombocytopenia.
abstract: BACKGROUND
  Thrombocytopenia is a serious side effect following high-dose chemotherapy or whole-body irradiation. For many patients, a hematopoietic stem cell (HSC) transplant is required as part of the treatment or to restore the integrity of the hematopoietic system. In this article, we first review the origin of thrombocytopenia in the context of umbilical cord blood (UCB) transplantation and current cellular therapies developed to overcome this condition. Results obtained in recent clinical trials and in the laboratory using a mouse-based xenograft model were also discussed. Second, we investigate the kinetic of human platelet production in two immunodeficient mouse strains transplanted with UCB cells to determine which of the two is better suited to measure the thrombopoietic potential of human hematopoietic cells.
  
  
  METHODS
  NOD/SCID/IL2Rγ(null)  or NOD.CB17-Prkdcscid/NcrCrl (NOD/SCID) mice were transplanted with ex vivo expanded UCB cells. Human platelet levels and marrow engraftments were measured by cytometry analyses.
  
  
  RESULTS
  Human platelets appeared earlier and at greater levels in the NOD/SCID/IL2Rγ(null)  mouse strain. Consistent with these results and previous reports, human marrow engraftment was also greater in the IL2Rγ(null) -based NOD/SCID mice.
  
  
  CONCLUSIONS
  The NOD/SCID/IL2Rγ(null)  mouse strain is an ideal choice for preclinical studies aimed at measuring the in vivo thrombopoietic potential of human HPCs. Exploitation of such a model should facilitate the development of new cellular therapies aimed at improving hematological recoveries following HSC transplantation.
authors.affiliation: Department of Research and Development, Hema-Quebec, and Biochemistry and Microbiology Department, Laval University, Quebec, Canada. nicolas.pineault@hema-quebec.qc.ca
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pineault
authors.forename: Lucie
authors.initials: L
authors.lastname: Boyer
mesh_terms: D000818:Animals; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006085:Graft Survival; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010976:Platelet Count; D011828:Radiation Chimera; D013921:Thrombocytopenia / Q000503:physiopathology / Q000601:surgery*; D014183:Transplantation, Heterologous
chemical_list: D053631:Interleukin Receptor Common gamma Subunit