Towards in vivo amplification： Overcoming hurdles in theuse of hematopoietic stem cells in transplantation and genetherapy

• 来源期刊: 世界干细胞杂志：英文版（电子版）
• 学科: 医学
• 关键词: Gene therapy HEMATOPOIETIC stem cells In vivo SELECTION Chemical INDUCER of DIMERIZATION Chemo-selection LENTIVIRUS
• 年，卷（期）: 2015,（11）
• 页码范围: 1233-1250
• 页数: 18页
• 分类号: R

摘要

With the advent of safer and more efficient genetransfer methods, gene therapy has become a viablesolution for many inherited and acquired disorders.Hematopoietic stem cells （HSCs） are a prime cellcompartment for gene therapy aimed at correctingblood-based disorders, as well as those amenable tometabolic outcomes that can effect cross-correction.While some resounding clinical successes have recentlybeen demonstrated, ample room remains to increasethe therapeutic output from HSC-directed genetherapy. In vivo amplification of therapeutic cells is oneavenue to achieve enhanced gene product delivery.To date, attempts have been made to provide HSCswith resistance to cytotoxic drugs, to include druginduciblegrowth modules specific to HSCs, and toincrease the engraftment potential of transduced HSCs.This review aims to summarize amplification strategiesthat have been developed and tested and to discusstheir advantages along with barriers faced towardstheir clinical adaptation. In addition, next-generationstrategies to circumvent current limitations of specificamplification schemas are discussed.