[Immortalization of erythroid progenitors for in vitro large-scale red cell production]. / Immortalisation érythrocytaire pour production de globules rouges in vitro.
Transfus Clin Biol
; 24(3): 263-267, 2017 Sep.
Article
in Fr
| MEDLINE
| ID: mdl-28736161
ABSTRACT
Population ageing and increase in cancer incidence may lead to a decreased availability of red blood cell units. Thus, finding an alternative source of red blood cells is a highly relevant challenge. The possibility to reproduce in vitro the human erythropoiesis opens a new era, particularly since the improvement in the culture systems allows to produce erythrocytes from induced-Pluripotent Stem Cells (iPSCs), or CD34+ Hematopoietic Stem Cells (HSCs). iPSCs have the advantage of in vitro self-renewal, but lead to poor amplification and maturation defects (high persistence of nucleated erythroid precursors). Erythroid differentiation from HSC allows a far better amplification and adult-like hemoglobin synthesis. But the inability of these progenitors to self-renew in vitro remains a limit in their use as a source of stem cells. A major improvement would consist in immortalizing these erythroid progenitors so that they could expand indefinitively. Inducible transgenesis is the first way to achieve this goal. To date, the best immortalized-cell models involve strong oncogenes induction, such as c-Myc, Bcl-xL, and mostly E6/E7 HPV16 viral oncoproteins. However, the quality of terminal differentiation of erythroid progenitors generated by these oncogenes is not optimal yet and the long-term stability of such systems is unknown. Moreover, viral transgenesis and inducible expression of oncogenes raise important problems in term of safety, since the enucleation rate is not 100% and no nucleated cells having replicative capacities should be present in the final product.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Erythroid Precursor Cells
/
Erythrocyte Transfusion
/
Erythropoiesis
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
Fr
Journal:
Transfus Clin Biol
Journal subject:
HEMATOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Francia