Abstract
Human hematopoiesis can be supported in beige/nude/XID (bnx) mice by coinjection of human bone marrow stromal cells engineered to secrete human interleukin 3 (HuIL-3). The major limitation is a total absence of human B cell development in the mice, which could he due to supraphysiological levels of HuIL-3 in the circulation. In an effort to obtain human B lymphoid, as well as T lymphoid and myeloid cell development in the mice, CD34+ cells were coinjected with human marrow stromal cells engineered to secrete human IL-2, IL-7, stem cell factor or FLT3 ligand, ± IL-3. No single factor other than IL-3 supported sustained human hematopoiesis in the mice, although cytokines were expressed for four to six months post-transplantation. Production of both HuIL-3 and IL-7 in the mice supported extrathymic development of human T lymphocytes, but no B cells, myeloid cells, or clonogenic progenitors were detected. Human B cells were not produced front CD34+ cells in the bnx mice under any condition tested. Another limitation to the bnx/Hu system is a lack of maturation of human red blood cells, although BFU-E are maintained. Stromal cells secreting human erythropoietin and IL-3 were cotransplanted into mice with HuCD34+ cells and an increase in hematocrit from 40%-45% to 80%-85% resulted, with production of human and murine red blood cells. Unfortunately, all mice (n = 9) suffered strokes, displayed paralysis and died within three weeks. The bnx/Hu cotransplantation model provides an interesting system in which to study human hematopoietic cell differentiation under the influence of various cytokines.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 443-454 |
| Number of pages | 12 |
| Journal | Stem Cells |
| Volume | 15 |
| Issue number | 6 |
| State | Published - 1997 |
| Externally published | Yes |
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Keywords
- Differentiation
- Marrow stroma immune deficient mice
- Retroviral-mediated transduction
- Stem cells
- Xenotransplantation
ASJC Scopus subject areas
- Cell Biology
Cite this
Long-term cytokine production from engineered primary human stromal cells influences human hematopoiesis in an in vivo xenograft model. / Dao, Mo A.; Pepper, Karen A.; Nolta, Jan.
In: Stem Cells, Vol. 15, No. 6, 1997, p. 443-454.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Long-term cytokine production from engineered primary human stromal cells influences human hematopoiesis in an in vivo xenograft model
AU - Dao, Mo A.
AU - Pepper, Karen A.
AU - Nolta, Jan
PY - 1997
Y1 - 1997
N2 - Human hematopoiesis can be supported in beige/nude/XID (bnx) mice by coinjection of human bone marrow stromal cells engineered to secrete human interleukin 3 (HuIL-3). The major limitation is a total absence of human B cell development in the mice, which could he due to supraphysiological levels of HuIL-3 in the circulation. In an effort to obtain human B lymphoid, as well as T lymphoid and myeloid cell development in the mice, CD34+ cells were coinjected with human marrow stromal cells engineered to secrete human IL-2, IL-7, stem cell factor or FLT3 ligand, ± IL-3. No single factor other than IL-3 supported sustained human hematopoiesis in the mice, although cytokines were expressed for four to six months post-transplantation. Production of both HuIL-3 and IL-7 in the mice supported extrathymic development of human T lymphocytes, but no B cells, myeloid cells, or clonogenic progenitors were detected. Human B cells were not produced front CD34+ cells in the bnx mice under any condition tested. Another limitation to the bnx/Hu system is a lack of maturation of human red blood cells, although BFU-E are maintained. Stromal cells secreting human erythropoietin and IL-3 were cotransplanted into mice with HuCD34+ cells and an increase in hematocrit from 40%-45% to 80%-85% resulted, with production of human and murine red blood cells. Unfortunately, all mice (n = 9) suffered strokes, displayed paralysis and died within three weeks. The bnx/Hu cotransplantation model provides an interesting system in which to study human hematopoietic cell differentiation under the influence of various cytokines.
AB - Human hematopoiesis can be supported in beige/nude/XID (bnx) mice by coinjection of human bone marrow stromal cells engineered to secrete human interleukin 3 (HuIL-3). The major limitation is a total absence of human B cell development in the mice, which could he due to supraphysiological levels of HuIL-3 in the circulation. In an effort to obtain human B lymphoid, as well as T lymphoid and myeloid cell development in the mice, CD34+ cells were coinjected with human marrow stromal cells engineered to secrete human IL-2, IL-7, stem cell factor or FLT3 ligand, ± IL-3. No single factor other than IL-3 supported sustained human hematopoiesis in the mice, although cytokines were expressed for four to six months post-transplantation. Production of both HuIL-3 and IL-7 in the mice supported extrathymic development of human T lymphocytes, but no B cells, myeloid cells, or clonogenic progenitors were detected. Human B cells were not produced front CD34+ cells in the bnx mice under any condition tested. Another limitation to the bnx/Hu system is a lack of maturation of human red blood cells, although BFU-E are maintained. Stromal cells secreting human erythropoietin and IL-3 were cotransplanted into mice with HuCD34+ cells and an increase in hematocrit from 40%-45% to 80%-85% resulted, with production of human and murine red blood cells. Unfortunately, all mice (n = 9) suffered strokes, displayed paralysis and died within three weeks. The bnx/Hu cotransplantation model provides an interesting system in which to study human hematopoietic cell differentiation under the influence of various cytokines.
KW - Differentiation
KW - Marrow stroma immune deficient mice
KW - Retroviral-mediated transduction
KW - Stem cells
KW - Xenotransplantation
UR - http://www.scopus.com/inward/record.url?scp=0030831145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030831145&partnerID=8YFLogxK
M3 - Article
C2 - 9402657
AN - SCOPUS:0030831145
VL - 15
SP - 443
EP - 454
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 6
ER -