ESTABLISHMENT OF RHESUS BONE MARROW CHIMERAS

恒河猴骨髓嵌合体的建立

基本信息

  • 批准号:
    6453768
  • 负责人:
  • 金额:
    $ 11.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-05-01 至 2002-04-30
  • 项目状态:
    已结题

项目摘要

In vivo evaluation of candidate stem cell populations has traditionally utilized either lethal irradiation experiments or SCID/NOD-mice To explore alternatives in a model that could examine both human and monkey cells, we have developed a fetal chimera model First trimester, immune incompetent rhesus fetuses have been transplanted with human CD34+ cells by ultrasound guided intraperitoneal injection On evaluation at birth and during the first 12 months of life, we have demonstrated persistent chimerism of human hematopoietic cells Chimerism is highest in the bone marrow (5-10% of CD34+ cells are of human phenotype) Chimerism in the peripheral blood varies between mononuclear fractions from 0 1-4% However, the majority of human CD34+ cells in the bone marrow are apoptotic This may explain the discordant level of engraftment in the bone marrow as compared to the peripheral blood We have identified a putative CD34- hematopoietic stem cell population in macaques Although in vitro experiments suggest that these cells have the expected in vitro characteristics of HSC (multipotency, highly enriched for LTC-IC), demonstration that rhesus CD34- SP cells contain HSC requires in vivo experiments showing long-term multilineage hematopoiesis Other investigators utilizing rhesus macaques to characterize HSC have typically examined hematopoietic reconstitution of lethally irradiated macaques In order to assess the engraftment capacity of the SP cells in an alternative model, we created male-female hematopoietic chimeras 10,000 rhesus SP cells were FACS purified from an SPF donor male animal and transplanted into a female recipient at 70 days of gestation At approximately 60 - 75 days of gestation, the SP cells were injected into the fetal peritoneal cavity The SP cells were resuspended in 1x106 irradiated (10,000 Rads) maternal red blood cells in 100 ml of seru m free PBS Maternal red cells were used as a means to increase the density of tranplanted cells as the number of SP cells was very small A source of cells that could not contribute to engraftment was selected so as not to confuse the results Ultrasound-guided intraperitoneal injections were carried out by Dr Tom Shipp, an obstetrician/gynecologist at Massachusetts General Hospital This was accomplished using ultrasound guidance to insert a 22 gauge spinal needle through the maternal abdominal wall, uterus and fetal abdominal wall We allowed the mother to carry the pregnancy until just prior to term, at which point the baby was delivered by cesarean section The evaluation of chimerism was performed using a PCR reaction specific for Y chromosome We have been able to achieve 1-10% chimerism in a rhesus-rhesus macaque model using this approach To demonstrate the feasibility of establishing mixed hematopoietic chimerism using a fetal transplant model, we performed mixed lym phocyte reactions against donor and an unrelated third party PBMCs Four of the animals who demonstrated engraftment using Y chromosome PCR, exhibit in vitro tolerance to donor PBMCs This demonstrates clearly that mixed chimerism has been achieved and set the precedence for using this model for the passive transfer of autologous CTL Furthermore, this data is consistent with what has been demonstrated in the murine model in showing that only a low level (0 01%) of hematopoietic chimerism is required in order to induce tolerance to donor PBMCs These studies continue in an attempt to optimise the model and determine the in vivo engraftment characteristics of various hematopoietic progenitor subsets Establishment of this model should prove useful in characterizing novel populations of human hematopoietic stem cells
候选干细胞群的体内评价

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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M ROSENZWEIG其他文献

M ROSENZWEIG的其他文献

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{{ truncateString('M ROSENZWEIG', 18)}}的其他基金

ESTABLISHMENT OF RHESUS BONE MARROW CHIMERAS
恒河猴骨髓嵌合体的建立
  • 批准号:
    6591322
  • 财政年份:
    2002
  • 资助金额:
    $ 11.11万
  • 项目类别:
STEM CELL GENE THERAPY USING LONG TERM BONE MARROW CULTURE TRANSDUCTION PROTOCOL
使用长期骨髓培养转导方案的干细胞基因治疗
  • 批准号:
    6591288
  • 财政年份:
    2002
  • 资助金额:
    $ 11.11万
  • 项目类别:
IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES
恒河猴 T 细胞更新的体内分析
  • 批准号:
    6591317
  • 财政年份:
    2002
  • 资助金额:
    $ 11.11万
  • 项目类别:
EXPRESSION OF BCL 2 IN SIV INFECTED THYMIC TISSUE
BCL 2 在 SIV 感染的胸腺组织中的表达
  • 批准号:
    6591316
  • 财政年份:
    2002
  • 资助金额:
    $ 11.11万
  • 项目类别:
FLT LIGAND PERIPHERAL BLOOD STEM CELL MOBILIZATION FOR STEM CELL GENE THERAPY
用于干细胞基因治疗的 FLT 配体外周血干细胞动员
  • 批准号:
    6591324
  • 财政年份:
    2002
  • 资助金额:
    $ 11.11万
  • 项目类别:
XENOGENEIC THYMIC TRANSPLANTATION AS AN ADJUNCT TO TREATMENT OF AIDS
异种胸腺移植作为艾滋病治疗的辅助手段
  • 批准号:
    6591306
  • 财政年份:
    2002
  • 资助金额:
    $ 11.11万
  • 项目类别:
EXPRESSION OF BCL 2 IN SIV INFECTED THYMIC TISSUE
BCL 2 在 SIV 感染的胸腺组织中的表达
  • 批准号:
    6453762
  • 财政年份:
    2001
  • 资助金额:
    $ 11.11万
  • 项目类别:
IN VIVO ANALYSIS OF T CELL TURNOVER IN RHESUS MACAQUES
恒河猴 T 细胞更新的体内分析
  • 批准号:
    6453763
  • 财政年份:
    2001
  • 资助金额:
    $ 11.11万
  • 项目类别:
STEM CELL GENE THERAPY USING LONG TERM BONE MARROW CULTURE TRANSDUCTION PROTOCOL
使用长期骨髓培养转导方案的干细胞基因治疗
  • 批准号:
    6453734
  • 财政年份:
    2001
  • 资助金额:
    $ 11.11万
  • 项目类别:
FLT LIGAND PERIPHERAL BLOOD STEM CELL MOBILIZATION FOR STEM CELL GENE THERAPY
用于干细胞基因治疗的 FLT 配体外周血干细胞动员
  • 批准号:
    6453770
  • 财政年份:
    2001
  • 资助金额:
    $ 11.11万
  • 项目类别:

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