Multiorgan engraftment and differentiation of mouse-induced pluripotent stem cells in rats: a roadmap towards personalised stem cell medicine

Saeid Amanpour, Zahra Mazaheri, Javad Alizadeh, Saeid Mohammadnejad, Mohammad Vasei, Karim Nayernia
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Abstract

Tissue engineering and regenerative are aiming at generating tissues to replace damaged and deteriorated organs. Recently, tissue engineering was applied to generate artificial skin for burn patients, tissue engineered trachea, cartilage for knee-replacement procedures, urinary bladder, urethra substitutes and offered cellular therapies for the treatment of urinary incontinence. The major advantage of tissue engineering approach over traditional organ transplantation is to circumvent the problem of organ shortage. Tissues reconstructed from readily available patents' stem cells induced no immunogenicity when reimplanted in the patient. However, pluripotent stem cells are major limited factors in regenerating new tissues. To overcome these problems, we developed a new technology called as ‘invivo interspecies tissue engineering’ (INVITE) and used the potential of induced pluripotent stem cells (iPSCs) to regenerate new tissues in a host organism. As a model, we used the mouse pluripotent stem cells to assess the potential of these cells to regenerate mouse tissues in rat. Three chimeric rats have been generated by mouse-induced pluripotent stem cells assessed by monitoring of green fluorescence protein (GFP) and polymerase chain reaction (PCR) assays. This study shows clearly that mouse-induced pluripotent stem cells are able to engraft in rat embryos and are capable to differentiate to multiple tissues. Beside the enormous important application of in vivo tissue engineering in human to develop new therapeutic approaches through regenerating new tissues, this model offers an accessible system for study of organ development and a valuable tool for personalised drug screening and a novel approach for personalised stem cell-based tissue regeneration.

Abstract Image

小鼠诱导的多能干细胞在大鼠体内的多器官移植和分化:走向个性化干细胞医学的路线图
组织工程和再生的目标是生成组织来替代受损和退化的器官。最近,组织工程被应用于烧伤患者的人造皮肤、组织工程气管、膝关节置换手术的软骨、膀胱、尿道替代品,并为治疗尿失禁提供了细胞疗法。与传统的器官移植方法相比,组织工程方法的主要优点是避免了器官短缺的问题。由现成的专利干细胞重建的组织在重新植入患者体内时没有产生免疫原性。然而,多能干细胞是再生新组织的主要限制因素。为了克服这些问题,我们开发了一种称为“体内物种间组织工程”(INVITE)的新技术,并利用诱导多能干细胞(iPSCs)的潜力在宿主生物中再生新组织。作为模型,我们使用小鼠多能干细胞来评估这些细胞在大鼠体内再生小鼠组织的潜力。用小鼠诱导的多能干细胞产生了3只嵌合大鼠,并进行了绿色荧光蛋白(GFP)和聚合酶链反应(PCR)检测。本研究清楚地表明,小鼠诱导的多能干细胞能够移植到大鼠胚胎中,并能够分化成多种组织。除了体内组织工程在人体中通过再生新组织开发新的治疗方法的巨大重要应用外,该模型还为器官发育研究提供了一个可访问的系统,为个性化药物筛选提供了有价值的工具,并为个性化干细胞组织再生提供了一种新方法。
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