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.
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.
Glimm
Hanno
H
Department of Internal Medicine I, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg, Germany.
Schmidt
Manfred
M
Fischer
Marlene
M
Klingenberg
Silke
S
Lange
Winand
W
Waller
Cornelius F
CF
Eaves
Connie J
CJ
von Kalle
Christof
C
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
D018952:Antigens, CD34; D006133:Growth Substances; D001613:beta 2-Microglobulin