Induced pluripotent stem cells： Mechanisms, achievementsand perspectives in farm animals

• 作者: Dharmendra Kumar Thirumala R Talluri Taruna Anand Wilfried A Kues
• 来源期刊: 世界干细胞杂志：英文版（电子版）
• 学科: 医学
• 关键词: REPROGRAMMING Large ANIMAL models STEMNESS CHIMERA GERMLINE transmission Inducedpluripotent stem cells Gene delivery
• 年，卷（期）: 2015,（2）
• 页码范围: 315-328
• 页数: 14页
• 分类号: R

摘要

Pluripotent stem cells are unspecialized cells withunlimited self-renewal, and they can be triggered todifferentiate into desired specialized cell types. Thesefeatures provide the basis for an unlimited cell sourcefor innovative cell therapies. Pluripotent cells also allowto study developmental pathways, and to employ themor their differentiated cell derivatives in pharmaceuticaltesting and biotechnological applications. Via blastocystcomplementation, pluripotent cells are a favoured toolfor the generation of genetically modified mice. Therecently established technology to generate an inducedpluripotency status by ectopic co-expression of thetranscription factors Oct4, Sox2, Klf4 and c-Myc allowsto extending these applications to farm animal species,for which the derivation of genuine embryonic stemcells was not successful so far. Most induced pluripotentstem （iPS） cells are generated by retroviral or lentiviraltransduction of reprogramming factors. Multiple viralintegrations into the genome may cause insertionalmutagenesis and may increase the risk of tumourformation. Non-integration methods have been reportedto overcome the safety concerns associated withretro and lentiviral-derived iPS cells, such as transientexpression of the reprogramming factors using episomalplasmids, and direct delivery of reprogrammingmRNAs or proteins. In this review, we focus on themechanisms of cellular reprogramming and currentmethods used to induce pluripotency. We also highlightproblems associated with the generation of iPS cells. Anincreased understanding of the fundamental mechanismsunderlying pluripotency and refining the methodology ofiPS cell generation will have a profound impact on futuredevelopment and application in regenerative medicineand reproductive biotechnology of farm animals.