Improved engraftment of human cord blood stem cells in NOD/LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients.

Authors

P A. Lowry
L D. ShultzFollow
D L. Greiner
R M. Hesselton
E L. Kittler
C Y. Tiarks
S S. Rao
J Reilly
J H. Leif
H Ramshaw
F M. Stewart
P J. Quesenberry

Document Type

Article

Publication Date

1996

Keywords

Female, Fetal-Tissue-Transplantation, Graft-Survival, Hematopoietic-Stem-Cell-Transplantation, Human, Mice, Mice-Inbred-NOD, Mice-SCID, Pregnancy, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Transplantation-Heterologous, Whole-Body-Irradiation

First Page

15

Last Page

23

JAX Source

Biol Blood Marrow Transplant 1996 Feb;2(1):15-23

Grant

AI30389/AI/NIAID, DK36024/DK/NIDDK

Abstract

Human lymphoematopoietic stem cells engraft in irradiated immunodeficient mice that are homozygous for the severe combined immunodeficiency (scid) mutation. Engraftment levels in C.B-17-scid/scid mice, however, have been low and transient, decreasing the utility of this model for investigation of the development potential and function of human stem cells. In the present study, we have used NOD/LtSz-scid/scid mice as recipients and human cord blood as a source of donor stem cells. Our results demonstrate that NOD/LtSz-scid/scid mice support approximately fivefold higher levels of human stem cell marrow engraftment than do C.B-17-scid/scid mice. Human CD34+ cells are present in the marrow of recipient mice, and the engrafted cells readily peripheralize to the circulation of the host. Terminal differentiation of the stem and progenitor cells into mature progeny is limited. Using a multiple-day injection protocol developed in mice, which allows engraftment of stem cells between congenic mice in the absence of irradiation preconditioning, we observed high levels of human cell engraftment in unirradiated NOD/LtSz-scid/scid recipients after three or five consecutive-day injections. These results demonstrate that NOD/LtSz-scid/scid mice support high levels of human stem cell engraftment and that xenogeneic lymphohematopoietic stem cells can engraft in unirradiated hosts without the need for ablative reconditioning. This model will be useful for the in vivo investigation of human stem cells and for the preclinical analysis of human stem cells for transplantation.

Recommended Citation

Lowry PA, Shultz LD, Greiner DL, Hesselton RM, Kittler EL, Tiarks CY, Rao SS, Reilly J, Leif JH, Ramshaw H, Stewart FM, Quesenberry PJ. Improved engraftment of human cord blood stem cells in NOD/LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients. Biol Blood Marrow Transplant 1996 Feb;2(1):15-23