TY - JOUR
T1 - Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice
AU - Vormoor, Josef
AU - Lapidot, Tsvee
AU - Pflumio, Françoise
AU - Risdon, Grant
AU - Patterson, Bruce
AU - Broxmeyer, Hal E.
AU - Dick, John E.
PY - 1994/5/1
Y1 - 1994/5/1
N2 - Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)-fractionated human cord blood cells were transplanted into sublethally irradiated severe combined immunodeficient (SCID) mice. High levels of multilineage engraftment, including myeloid and lymphoid lineages, were obtained with 80% of the donor samples as assessed by DNA analysis, fluorescence-activated cell sorting (FACS), and morphology. In contrast to previous and concurrent studies with adult human bone marrow (BM), treatment with human cytokines was not required to establish high-level human cell engraftment, suggesting that neonatal cells either respond differently to the murine microenvironment or they provide their own cytokines in a paracrine fashion. Committed and multipotential myelo-erythroid progenitors were detected using in vitro colony assays and FACS analysis of the murine BM showed the presence of immature CD34+ cells. In addition, human hematopoiesis was maintained for at least 14 weeks providing further evidence that immature hematopoietic precursors had engrafted the murine BM. This in vivo model for human cord blood-derived hematopoiesis will be useful to gain new insights into the biology of neonatal hematopoietic cells and to evaluate their role in gene therapy. There is growing evidence that there are ontogeny-related changes in immature human hematopoietic cells, and therefore, the animal models we have developed for adult and neonatal human hematopoiesis provide useful tools to evaluate these changes in vivo.
AB - Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)-fractionated human cord blood cells were transplanted into sublethally irradiated severe combined immunodeficient (SCID) mice. High levels of multilineage engraftment, including myeloid and lymphoid lineages, were obtained with 80% of the donor samples as assessed by DNA analysis, fluorescence-activated cell sorting (FACS), and morphology. In contrast to previous and concurrent studies with adult human bone marrow (BM), treatment with human cytokines was not required to establish high-level human cell engraftment, suggesting that neonatal cells either respond differently to the murine microenvironment or they provide their own cytokines in a paracrine fashion. Committed and multipotential myelo-erythroid progenitors were detected using in vitro colony assays and FACS analysis of the murine BM showed the presence of immature CD34+ cells. In addition, human hematopoiesis was maintained for at least 14 weeks providing further evidence that immature hematopoietic precursors had engrafted the murine BM. This in vivo model for human cord blood-derived hematopoiesis will be useful to gain new insights into the biology of neonatal hematopoietic cells and to evaluate their role in gene therapy. There is growing evidence that there are ontogeny-related changes in immature human hematopoietic cells, and therefore, the animal models we have developed for adult and neonatal human hematopoiesis provide useful tools to evaluate these changes in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0028281703&partnerID=8YFLogxK
U2 - 10.1182/blood.v83.9.2489.bloodjournal8392489
DO - 10.1182/blood.v83.9.2489.bloodjournal8392489
M3 - Article
C2 - 7513200
AN - SCOPUS:0028281703
SN - 0006-4971
VL - 83
SP - 2489
EP - 2497
JO - Blood
JF - Blood
IS - 9
ER -