Phorbol ester induced ex vivo expansion of rigorously-defined phenotypic but not functional human cord blood hematopoietic stem cells: a cautionary tale …

Y Chen, C Yao, Y Teng, R Jiang, X Huang, S Liu… - Leukemia, 2019 - nature.com
Y Chen, C Yao, Y Teng, R Jiang, X Huang, S Liu, J Wan, HE Broxmeyer, B Guo
Leukemia, 2019nature.com
Hematopoietic stem cells (HSCs) are a rare population residing at the apex of the
hematopoietic hierarchy [1]. HSCs have the capacity to self-renew and differentiate into all
blood cell types, thus they play a key role in hematopoietic cell transplantation (HCT)[2].
HCT is widely used as a curative therapy for numerous malignant and nonmalignant
hematological and even non-hematological diseases [3]. The fast developing field of gene
editing techniques, including ZFNs, TALENs and CRISPR-Cas9, broaden usage of HCT in …
Hematopoietic stem cells (HSCs) are a rare population residing at the apex of the hematopoietic hierarchy [1]. HSCs have the capacity to self-renew and differentiate into all blood cell types, thus they play a key role in hematopoietic cell transplantation (HCT)[2]. HCT is widely used as a curative therapy for numerous malignant and nonmalignant hematological and even non-hematological diseases [3]. The fast developing field of gene editing techniques, including ZFNs, TALENs and CRISPR-Cas9, broaden usage of HCT in clinical therapy of diseases caused by genetic mutations [4]. ie β-thalassaemia or Sickle Cell Disease (SCD) may possibly be interrogated by CRISPR based gene editing of β-globin in HSCs from patients [5]. However, efficient gene editing and infusion of the gene edited HSC into patients requires sufficient numbers of donor HSC. In addition, when cord blood (CB) is used as the source of HSC for HCT, rare HSC numbers in single CB units may lead to delayed hematopoietic recovery in recipients [6]. It is thus important in some cases to develop efficient means that can overcome limited HSC numbers to enhance the efficacy of HCT.
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