Projects per year
Abstract / Description of output
We have developed a robust, Good Manufacturing Practice‐compatible differentiation protocol capable of producing scalable quantities of red blood cells (RBCs) from human pluripotent stem cells (hPSCs). However, translation of this protocol to the clinic has been compromised because the RBCs produced are not fully mature; thus, they express embryonic and fetal, rather than adult globins, and they do not enucleate efficiently. Based on previous studies, we predicted that activation of exogenous HOXB4 would increase the production of hematopoietic progenitor cells (HPCs) from hPSCs and hypothesized that it might also promote the production of more mature, definitive RBCs. Using a tamoxifen‐inducible HOXB4‐ERT2 expression system, we first demonstrated that activation of HOXB4 does increase the production of HPCs from hPSCs as determined by colony‐forming unit culture activity and the presence of CD43+CD34+ progenitors. Activation of HOXB4 caused a modest, but significant, increase in the proportion of immature CD235a+/CD71+ erythroid cells. However, this did not result in a significant increase in more mature CD235a+/CD71− cells. RBCs produced in the presence of enhanced HOXB4 activity expressed embryonic (ε) and fetal (γ) but not adult (β) globins, and the proportion of enucleated cells was comparable to that of the control cultures. We conclude that programming with the transcription factor HOXB4 increases the production of hematopoietic progenitors and immature erythroid cells but does not resolve the inherent challenges associated with the production of mature adult‐like enucleated RBCs.
Original language | English |
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Pages (from-to) | 981-990 |
Journal | Stem Cells Translational Medicine |
Volume | 5 |
Issue number | 8 |
Early online date | 28 Jun 2016 |
DOIs | |
Publication status | Published - Aug 2016 |
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Dive into the research topics of 'Enforced Expression of HOXB4 in Human Embryonic Stem Cells Enhances the Production of Hematopoietic Progenitors but Has No Effect on the Maturation of Red Blood Cells'. Together they form a unique fingerprint.Projects
- 3 Finished
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ECAT (100468) Analysis of the early development of human haematopoietic stem and progenitor cells
6/05/13 → 8/10/17
Project: Research
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Proof of principle: human embryonic stem cell derived red cell concentrates for clinical transfusion
1/07/09 → 31/10/13
Project: Research
Profiles
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Lesley Forrester
- Deanery of Clinical Sciences - UoE Retired Staff
- Centre for Regenerative Medicine
- Centre for Inflammation Research
- Edinburgh Haematopoiesis Network
Person: Academic: Research Active , Affiliated Independent Researcher