Effects of allogeneic support cells on human hematopoietic stem cell engraftment in a novel immune deficient mouse transplant system

Jesusa M G Arevalo, Scott S. Case, Donald B. Kohn, Jan Nolta

Research output: Contribution to journalArticle

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Abstract

It has become a popular practice to add irradiated or live CD34- cells to purified human HSC as support in xenogeneic bone marrow transplantation, to obtain enhanced levels of engraftment in immune deficient mice. We sought to examine this phenomenon in our new strain of mice, the nude/NOD/SCID. This strain is a product of several years of backcrossing beige/nude/xid (bnx) mice into the NOD/SCID strain. Nude/NOD/SCID mice have a significantly longer lifespan than the parental NOD/SCID strain, due to the absence of thymic tissue where the lethal thymoma can arise. The goal of the current studies was to add back the CD34- cells from autologous vs. allogeneic sources, to try to boost engraftment levels from CD34+ progenitors isolated from human umbilical cord blood. In some experiments, the CD34+ cells were marked with lentiviral vectors carrying the EGFP marker, to allow definitive discrimination between the transplanted CD34+ cells and the non-transduced support cells. Human cells engrafted in the bone marrow, spleen, and blood of the nude/NOD/SCID mice, and multilineage (lymphoid and myeloid) engraftment was detected, with a portion of each lineage retaining expression of EGFP 1 2 months post-transplantation. The average percentages of human CD45+ cells in mice transplanted with allogeneic CD34- cells added to the CD34+ transplant inoculum were as follows: BM (N=7) = 6.4 ±3.2%, spleen = 13.9 ±2.2%, and blood = 5.1 ±1.7%. However, when autologous CD34- cells were added back to the CD34+ cells, the human cell engraftment levels were as follows: BM (N=4) = 0.8 ±0.1%, spleen = 1.9 ±0.7% and blood = 2.1 ±0.3%. When CD34+ cells were transplanted alone, the human cell engraftment levels were: BM (N=9) = 4.3 ±1.0%, spleen = 3.0 ±1.5% and blood = 2.5 ±1.4%. In summary, the best engraftment levels were obtained when allogeneic human CD34- cells were transplanted into nude/NOD/SCID mice along with the CD34+ stem cell inoculum.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART I
StatePublished - 2000
Externally publishedYes

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Transplants
Hematopoietic Stem Cells
Stem cells
Blood
Cells
Inbred NOD Mouse
Bone
SCID Mice
Spleen
Tissue
Nude Mice
Thymoma
Inbreeding
Experiments
Bone Marrow Transplantation
Fetal Blood

ASJC Scopus subject areas

  • Hematology

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Effects of allogeneic support cells on human hematopoietic stem cell engraftment in a novel immune deficient mouse transplant system. / Arevalo, Jesusa M G; Case, Scott S.; Kohn, Donald B.; Nolta, Jan.

In: Blood, Vol. 96, No. 11 PART I, 2000.

Research output: Contribution to journalArticle

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title = "Effects of allogeneic support cells on human hematopoietic stem cell engraftment in a novel immune deficient mouse transplant system",
abstract = "It has become a popular practice to add irradiated or live CD34- cells to purified human HSC as support in xenogeneic bone marrow transplantation, to obtain enhanced levels of engraftment in immune deficient mice. We sought to examine this phenomenon in our new strain of mice, the nude/NOD/SCID. This strain is a product of several years of backcrossing beige/nude/xid (bnx) mice into the NOD/SCID strain. Nude/NOD/SCID mice have a significantly longer lifespan than the parental NOD/SCID strain, due to the absence of thymic tissue where the lethal thymoma can arise. The goal of the current studies was to add back the CD34- cells from autologous vs. allogeneic sources, to try to boost engraftment levels from CD34+ progenitors isolated from human umbilical cord blood. In some experiments, the CD34+ cells were marked with lentiviral vectors carrying the EGFP marker, to allow definitive discrimination between the transplanted CD34+ cells and the non-transduced support cells. Human cells engrafted in the bone marrow, spleen, and blood of the nude/NOD/SCID mice, and multilineage (lymphoid and myeloid) engraftment was detected, with a portion of each lineage retaining expression of EGFP 1 2 months post-transplantation. The average percentages of human CD45+ cells in mice transplanted with allogeneic CD34- cells added to the CD34+ transplant inoculum were as follows: BM (N=7) = 6.4 ±3.2{\%}, spleen = 13.9 ±2.2{\%}, and blood = 5.1 ±1.7{\%}. However, when autologous CD34- cells were added back to the CD34+ cells, the human cell engraftment levels were as follows: BM (N=4) = 0.8 ±0.1{\%}, spleen = 1.9 ±0.7{\%} and blood = 2.1 ±0.3{\%}. When CD34+ cells were transplanted alone, the human cell engraftment levels were: BM (N=9) = 4.3 ±1.0{\%}, spleen = 3.0 ±1.5{\%} and blood = 2.5 ±1.4{\%}. In summary, the best engraftment levels were obtained when allogeneic human CD34- cells were transplanted into nude/NOD/SCID mice along with the CD34+ stem cell inoculum.",
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N2 - It has become a popular practice to add irradiated or live CD34- cells to purified human HSC as support in xenogeneic bone marrow transplantation, to obtain enhanced levels of engraftment in immune deficient mice. We sought to examine this phenomenon in our new strain of mice, the nude/NOD/SCID. This strain is a product of several years of backcrossing beige/nude/xid (bnx) mice into the NOD/SCID strain. Nude/NOD/SCID mice have a significantly longer lifespan than the parental NOD/SCID strain, due to the absence of thymic tissue where the lethal thymoma can arise. The goal of the current studies was to add back the CD34- cells from autologous vs. allogeneic sources, to try to boost engraftment levels from CD34+ progenitors isolated from human umbilical cord blood. In some experiments, the CD34+ cells were marked with lentiviral vectors carrying the EGFP marker, to allow definitive discrimination between the transplanted CD34+ cells and the non-transduced support cells. Human cells engrafted in the bone marrow, spleen, and blood of the nude/NOD/SCID mice, and multilineage (lymphoid and myeloid) engraftment was detected, with a portion of each lineage retaining expression of EGFP 1 2 months post-transplantation. The average percentages of human CD45+ cells in mice transplanted with allogeneic CD34- cells added to the CD34+ transplant inoculum were as follows: BM (N=7) = 6.4 ±3.2%, spleen = 13.9 ±2.2%, and blood = 5.1 ±1.7%. However, when autologous CD34- cells were added back to the CD34+ cells, the human cell engraftment levels were as follows: BM (N=4) = 0.8 ±0.1%, spleen = 1.9 ±0.7% and blood = 2.1 ±0.3%. When CD34+ cells were transplanted alone, the human cell engraftment levels were: BM (N=9) = 4.3 ±1.0%, spleen = 3.0 ±1.5% and blood = 2.5 ±1.4%. In summary, the best engraftment levels were obtained when allogeneic human CD34- cells were transplanted into nude/NOD/SCID mice along with the CD34+ stem cell inoculum.

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