BIOLOGICAL EFFECT OF LASER: APPLICATION TO STEM CELL TRANSPLANTATION

激光的生物学效应:在干细胞移植中的应用

基本信息

  • 批准号:
    7722561
  • 负责人:
  • 金额:
    $ 0.67万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-04-15 至 2009-03-31
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related macular degeneration (AMD) is the leading cause of blindness in the United States, for which there is no cure. It has devastating effects on the quality of life in the aging population interfering with everyday functions such as reading and driving, and has become a major public health concern. AMD is particularly amenable to cell-replacement therapy because the affected areas of retinal pigment epithelium (RPE, the tissue primarily affected by the disease) can be directly visualized, and transplantation of stem cells could be performed by subretinal injections using currently available surgical techniques. Autologous stem cell transplantation is the safest and, thus, clinically preferred approach in patients with AMD. This implies using adult stem cells obtained from an easily accessible and abundant tissue source from the same patient, such as bone marrow. Evidence that human bone marrow-derived stem cells (hBMSCs) are able to promote repair of neural tissues including RPE has been growing, although therapeutic avenues to promote homing and engraftment of hBMSCs into damaged or diseased tissues remain unclear. Xenotransplantation of human cells into early chick embryos has been proposed as an in vivo system for differentiation of human BMSCs into spinal cord neurons by our collaborators Darwin Prockop and Joel Glover. Here we utilize a robust, convenient and rapid in vivo engraftment and differentiation approach using primitive eyes of chick embryos for guiding the developmental program of hBMSCs towards their RPE differentiation. Embryonic optic neuroepithelium is more permissive for stem cell engraftment compared to adult ocular tissues and provides a natural developmental microenvironment for the donor stem cell differentiation in vivo within the native RPE developmental program. However, the engraftment efficiency of adult stem cells remains suboptimal. Thus, we propose to utilize laser energy to modulate interactions between hBMSCs and the recipient embryonic ocular microenvironment to improve the engraftment potential of the donor cells and enhance the recipient tissue permissiveness to stem cell incorporation. Specifically, we propose to use laser irradiation to: 1) Create a controllable intraocular injury mechanism prior to stem cell transplantation into the embryonic chick eye in order to inhibit the endogenous ocular cells from competing with the transplanted donor cells, and also to stimulate regenerative tissue response to enhance homing and engraftment of the donor cells; 2) Investigate the effects of low energy (e.g. sub-damage threshold) lasers of various wavelengths (such as 530, 690, 810 and 950 nm, but particularly 810 nm) on the recipient tissue permissiveness (i.e. irradiate the primitive chick eyes in ovo) and the donor cells engraftment potential (i.e. irradiate adult human stem cells in vitro prior to their transplantation); 3) Measure the oxygen concentration in the developing embryonic eye in ovo and to use these conditions to pre-condition the adult human stem cells prior to their transplantation in order to enhance their survival and engraftment, and also to evaluate the effect of laser irradiation of the embryonic chick eye on oxygen concentration in vivo; 4) Evaluate the effect of laser irradiation on the permissiveness of the retina/RPE complex in the adult RCS rat model of retinal degeneration (also see 1 and 2). In summary, the proposed studies of laser-assisted cell transplantation (LACT) provide the foundation for development of a broad therapeutic platform for a variety of poorly treatable diseases such as AMD.
该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金, 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说,它不一定是研究者的机构。 年龄相关性黄斑变性 (AMD) 是美国失明的主要原因,目前尚无治愈方法。它对老年人的生活质量产生毁灭性影响,干扰阅读和驾驶等日常功能,并已成为主要的公共卫生问题。 AMD 特别适合细胞替代疗法,因为视网膜色素上皮(RPE,主要受疾病影响的组织)的受影响区域可以直接可视化,并且可以使用当前可用的手术技术通过视网膜下注射进行干细胞移植。 自体干细胞移植是 AMD 患者最安全的临床首选方法。这意味着使用从同一患者容易获得且丰富的组织来源(例如骨髓)获得的成体干细胞。尽管促进 hBMSC 归巢和植入受损或患病组织的治疗途径尚不清楚,但越来越多的证据表明,人骨髓来源干细胞 (hBMSC) 能够促进包括 RPE 在内的神经组织修复。 我们的合作者 Darwin Prockop 和 Joel Glover 提出将人类细胞异种移植到早期鸡胚胎中作为将人类 BMSC 分化为脊髓神经元的体内系统。在这里,我们利用鸡胚原眼的稳健、方便、快速的体内植入和分化方法来指导 hBMSC 的发育程序向 RPE 分化。与成体眼组织相比,胚胎视神经上皮更容易植入干细胞,并为供体干细胞在天然 RPE 发育程序中体内分化提供自然的发育微环境。然而,成体干细胞的植入效率仍然不理想。 因此,我们建议利用激光能量调节 hBMSC 与受体胚胎眼部微环境之间的相互作用,以提高供体细胞的植入潜力并增强受体组织对干细胞掺入的许可性。具体来说,我们建议使用激光照射来:1)在干细胞移植到胚胎鸡眼之前创建可控的眼内损伤机制,以抑制内源性眼细胞与移植的供体细胞竞争,并刺激再生组织增强供体细胞归巢和植入的反应; 2) 研究不同波长(如530、690、810和950 nm,但特别是810 nm)的低能量(如亚损伤阈值)激光对受体组织许可性(即照射卵内原始雏鸡眼睛)的影响)和供体细胞的植入潜力(即在移植前对成人干细胞进行体外照射); 3) 测量卵内发育中胚胎眼的氧浓度,并利用这些条件在移植前对成人干细胞进行预处理,以提高其存活率和植入率,并评估激光照射对成体干细胞的影响。胚胎鸡眼对体内氧浓度的影响; 4) 评估激光照射对成年 RCS 大鼠视网膜变性模型中视网膜/RPE 复合体允许性的影响(另见 1 和 2)。 总之,拟议的激光辅助细胞移植(LACT)研究为开发针对多种难以治疗的疾病(例如 AMD)的广泛治疗平台奠定了基础。

项目成果

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TATIANA B KRASIEVA其他文献

TATIANA B KRASIEVA的其他文献

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{{ truncateString('TATIANA B KRASIEVA', 18)}}的其他基金

MPM STUDY OF ANIMAL SYNOVIUM TO OBTAIN INSIGHT INTO AFFECTS OF ARTHRITIS
对动物滑膜进行 MPM 研究以深入了解关节炎的影响
  • 批准号:
    8362631
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
  • 项目类别:
OPTICAL AND MOLECULAR APPROACHES TO THE STUDY OF CHEMICAL AGENTS
研究化学试剂的光学和分子方法
  • 批准号:
    8362624
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    2011
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    $ 0.67万
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    8362636
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    2011
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    $ 0.67万
  • 项目类别:
BIO-POD: PALLET MICRO-ARRAY FOR RARE CELL ANALYSIS
BIO-POD:用于稀有细胞分析的托盘微阵列
  • 批准号:
    8362628
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
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MULTI-PHOTON IMAGING OF ACTIN FILAMENT FORMATION AND MITOCHONDRIAL ENERGETICS
肌动蛋白丝形成和线粒体能量的多光子成像
  • 批准号:
    8362658
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
  • 项目类别:
COMBINED TWO PHOTON OPTICAL COHERENCE MICROSCOPY FOR INTRAVITAL FUNCT IMAGING
用于活体功能成像的组合两个光子光学相干显微镜
  • 批准号:
    8362594
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
  • 项目类别:
ACBT GLIOMA SPHEROIDS
ACBT 胶质瘤球体
  • 批准号:
    8362626
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
  • 项目类别:
GENOME WIDE SIRNA SCREENING IDENTIFIES NOVEL REGULATORS OF MELANIN SECRETION
全基因组 SIRNA 筛选鉴定出黑色素分泌的新型调节因子
  • 批准号:
    8362629
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
  • 项目类别:
NONINVASIVE IMAGING OF NEURAL STEM AND PRECURSOR CELL FUNCTIONS
神经干和前体细胞功能的无创成像
  • 批准号:
    8362632
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
  • 项目类别:
ROLE OF SMC COMPLEXES IN DNA REPAIR
SMC 复合物在 DNA 修复中的作用
  • 批准号:
    8362704
  • 财政年份:
    2011
  • 资助金额:
    $ 0.67万
  • 项目类别:

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