Stem Cell Differentiation: Long Term Follow Up

干细胞分化：长期随访

• 批准号: 6527985
• 负责人: BEVERLY J. TOROK-STORB
• 金额: $ 25.95万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527985
• 关键词: biopsy; bone marrow transplantation; cell differentiation; fluorescent in situ hybridization; homologous transplantation; human subject; long term survivor; patient oriented research; regeneration; sex chromosomes; stem cells

DESCRIPTION (provided by applicant): The proposed existence of adult, marrow derived stem cells that have retained the potential to generate muscle, liver, neurons, etc., is conceptually appealing. However the current data in support of this concept are more intriguing than compelling. To contribute to the resolution of this uncertainty we propose to investigate the contribution of donor marrow stem cells to skin, gut epithelium, liver, muscle, and marrow stroma. We hypothesize that if "plastic stem cells" originate or reside in marrow they will, with time and/or challenge, contribute to nonhematopoietic tissue regeneration. To test this hypothesis we propose to analyze tissue from patients who are long term survivors of sex mismatched allogeneic marrow transplantation. Currently there are more than 2,300 patients from 1 to 25 years post transplant, who are being actively followed for late complications by the Long Term Follow UP (LTFU) program of the Fred Hutchinson Cancer Research Center. These complications affect all organ systems including skin, eyes, GI tract, liver, lungs, muscles, connective tissue, bladder, kidneys, and central nervous system. Through the efforts of the LTFU office an aliquot of tissue biopsies obtained for diagnostic purposes will be made available for studies proposed here. Tissue samples from these patients will be evaluated in two ways: first, by standard fluorescence in situ hybridization (FISH) for detection of sex chromatin in histological sections; second, by ex vivo expansion of defined cell populations followed by FISH as well as polymerase chain reaction (pcr) amplification of donor versus host DNA. These strategies should improve the signal to noise ratio and make the detection of donor derived cells more reliable. The information gained should help define whether, and under what circumstances, marrow derived stem cells contribute to other tissues following allogeneic transplantation.

描述（由申请人提供）： 建议存在的成人，骨髓来源的干细胞，保留了 产生肌肉、肝脏、神经元等的潜力，在概念上 很吸引人。然而，目前支持这一概念的数据更多 有趣而不是引人注目。为解决这一问题做出贡献 不确定性，我们建议研究供体骨髓干细胞的贡献 细胞到皮肤、肠上皮、肝脏、肌肉和骨髓基质。我们 假设如果“可塑性干细胞”起源于或存在于骨髓中， 随着时间的推移和/或挑战， 再生为了验证这一假设，我们建议分析组织， 性别不匹配的同种异体骨髓长期存活的患者 移植目前有2,300多名患者从1岁到25岁 移植后10年，正在积极随访晚期并发症 由Fred哈钦森癌症中心的长期随访（LTFU）计划 研究中心这些并发症影响所有器官系统，包括皮肤， 眼睛、胃肠道、肝脏、肺、肌肉、结缔组织、膀胱、肾脏， 和中枢神经系统。通过长期信托基金办公室的努力， 为诊断目的获得的组织活检将提供给 在此提出的研究。将对这些患者的组织样本进行评价 方法有两种：一是通过标准荧光原位杂交（FISH） 检测组织切片中的性染色质;第二，通过离体 扩增确定的细胞群，然后进行FISH以及聚合酶 供体与宿主DNA的链式反应（PCR）扩增。这些策略 应提高信噪比，使供体的检测 衍生细胞更可靠。获得的信息应有助于确定 骨髓来源的干细胞是否以及在什么情况下有助于 同种异体移植后的其他组织。