On the feasibility of inducing tolerance in man: a study in the cynomolgus monkey

Brent, L.; Linch, David C.; Rodeck, CH; Nicolaides, Kypros H.; L, DeGiorgi; Sherwood, R. A.; Al-Imara, L.; Mew, J.; Socha, W. W.

doi:10.1016/0165-2478(89)90012-6

Cited by 17 publications

(15 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In one animal, where the total T-cell dose was 10 8 /kg, the animal died with massive hydrops fetalis with lymphocytic infiltrates on histologic exam, consisShields, Gaur, Gough et al e animals M98-179 and M99-080 did not have determinations of lineage-specific chimerism testing; f progenitor chimerism is from the initial evaluation ND = not determined tent with GVHD. Similar physical findings in the fetus have been previously reported when the marrow cell preparation was felt not to have been sufficiently T-cell depleted [18].…”

Section: Discussionsupporting

confidence: 73%

“…Based on the condition of the fetus at the time of delivery (lack of maceration or skin sloughing), the animal appeared to have died shortly before birth. Pathological examination of that animal showed hydropic changes and lymphocytic infiltrates in skin and subcutaneous tissue consistent with GVHD [18]. Attempts to grow cells from the fetal liver, bone marrow, and cord blood were not successful, and we were not able to quantitate the level of chimerism.…”

Section: Transplanted Animalsmentioning

confidence: 92%

“…Suspected in utero GVHD was made on the basis of hydrops fetalis and confirmed postnatally by histologic exam [18]. Pathologic GVHD was defined as lymphocytic infiltrates noted in skin, intestine, liver, or other tissues.…”

Section: Graft-versus-host Diseasementioning

confidence: 99%

“…This gestational age was chosen based on studies showing an optimal transplant time of ~0.38-0.46 gestation in fetal sheep [8] and others showing no chimerism in nonhuman primates when fetuses were transplanted at >0.44 gestation (baboons) [17] and >0.42 gestation (cynomolgus monkeys) [18]. The success of each fetal injection was confirmed by observing a small echogenic focus at the injection site representing a small amount of air purposely injected with the donor cells and by the presence of a small amount of abdominal fluid (ascites) [19].…”

Section: Fetal Transplantationmentioning

confidence: 99%

See 3 more Smart Citations

In Utero Hematopoietic Stem Cell Transplantation in Nonhuman Primates: The Role of T Cells

et al. 2003

View full text Add to dashboard Cite

In utero transplantation of hematopoietic stem cells is a promising treatment for immune and hematologic diseases of fetuses and newborns. Unfortunately, there are limited data from nonhuman primates and humans describing optimal transplantation conditions. The purpose of this investigation was to determine the effect of T-cell number on engraftment and the level of chimerism after in utero transplantation in nonhuman primates. CD34 + allogeneic adult bone marrow cells, obtained from the sire after G-CSF and stem cell factor administration, were transplanted into female fetal recipients. The average CD34 + cell dose was 3.0 × × 10 9 /kg (range, 9.9 × × 10 8 to 4.4 × × 10 9 ) and the T-cell dose ranged from 2.6 × × 10 5 to 1.1 × × 10 8 /kg. Chimerism was determined in peripheral blood subsets (CD2, CD13, and CD20) and in progenitor cell populations by using polymerase chain reaction. Chimerism was noted in seven of eight live-born animals. The level of chimerism in the progenitor population was related to the fetal T-cell dose (r = 0.64, p < 0.02). At the lowest T-cell dose (2.6 × × 10 5 /kg), no chimerism was detected. As the T-cell dose increased to 10 6-7 /kg, the level of chimerism increased. Adjusting the T-cell dose to 1.1 × × 10 8 /kg resulted in fatal graft-versus-host disease (GVHD). The results of this study emphasize the importance of T cells in facilitating donor cell engraftment and in producing GVHD in fetal nonhuman primates. Some animals achieved levels of chimerism in the marrow hematopoietic progenitor cell population that would likely have clinical relevance. However, the levels of chimerism in peripheral blood were too low for therapeutic benefit. Further studies are needed to test methods that are likely to enhance donor cell engraftment and peripheral blood levels of donor cells.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Transplanted Animalsmentioning

confidence: 92%

Section: Graft-versus-host Diseasementioning

confidence: 99%

Section: Fetal Transplantationmentioning

confidence: 99%

See 2 more Smart Citations

In Utero Hematopoietic Stem Cell Transplantation in Nonhuman Primates: The Role of T Cells

et al. 2003

View full text Add to dashboard Cite

show abstract

“…In this study the fetuses with chimerism died in the third trimester in utero for unknown reasons. Brent et al [88] injected 22 cynomolgus monkeys with paternal bone marrow. There was no evidence of chimerism in the late inoculated animals.…”

Section: Adull-lo-felus Transplantationmentioning

confidence: 99%

New Approaches in Bone Marrow Transplantation: The Utilization of Hematopoietic Stem Cells

Michejda

Peters²,

Vleeschouwer³

et al. 1990

Fetal Diagn Ther

View full text Add to dashboard Cite

show abstract

The Importance of Non-Human Primate Models for Pre-clinical Studies in Hematopoiesis

Szilàgyi

Mahmud

Bartholomew

2009

Allogeneic Stem Cell Transplantation

View full text Add to dashboard Cite

On the feasibility of inducing tolerance in man: a study in the cynomolgus monkey

Cited by 17 publications

References 12 publications

In Utero Hematopoietic Stem Cell Transplantation in Nonhuman Primates: The Role of T Cells

In Utero Hematopoietic Stem Cell Transplantation in Nonhuman Primates: The Role of T Cells

New Approaches in Bone Marrow Transplantation: The Utilization of Hematopoietic Stem Cells

The Importance of Non-Human Primate Models for Pre-clinical Studies in Hematopoiesis

Contact Info

Product

Resources

About