title: Evidence of similar effects of short-term culture on the initial repopulating activity of mobilized peripheral blood transplants assessed in NOD/SCID-beta2microglobulin(null) mice and in autografted patients.
abstract: OBJECTIVE
  Human mobilized peripheral blood (mPB) is known to contain high numbers of cells with rapid but short-term repopulating activity in NOD/SCID-beta2microglobulin(-/-) mice. Here we assessed the effect of short-term culture on these cells and compared the levels of retained activity with the pace of hematologic recovery in myeloablated patients transplanted with similarly cultured autografts of the same cells.
  
  
  METHODS
  In a phase 1 clinical study, mPB cells were collected from 6 advanced cancer patients. CD34(+) cells were then harvested, cultured for 3 days in the presence of early-acting growth factors, and transplanted, and posttransplant recovery of blood cell parameters monitored. Assays for primitive hematopoietic activity using both in vivo (in NOD/SCID-beta2microglobulin(-/-) mice) and in vitro (CFC and LTC-IC) endpoints were also performed on the cells pre- and posttransplant.
  
  
  RESULTS
  All patients showed event-free, timely leukocyte recoveries but slightly delayed platelet recoveries in some cases. During the 3-day period of culture, the CFCs doubled but the LTC-IC activity decreased (twofold), as did the short-term repopulating activity in NOD/SCID-beta2microglobulin(-/-) mice.
  
  
  CONCLUSIONS
  Patients can be transplanted with 3-day cultured autografts with minimal effects on hematologic recovery. This is associated with a variable but, on average, modest loss of short-term repopulating activity detectable in NOD/SCID-beta2microglobulin(-/-) mice.
authors.affiliation: Department of Internal Medicine I, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Glimm
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.forename: Marlene
authors.initials: M
authors.lastname: Fischer
authors.forename: Silke
authors.initials: S
authors.lastname: Klingenberg
authors.forename: Winand
authors.initials: W
authors.lastname: Lange
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Waller
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D018929:Cell Culture Techniques; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012038:Regeneration; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000172:deficiency
chemical_list: D018952:Antigens, CD34; D006133:Growth Substances; D001613:beta 2-Microglobulin