Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells
As cell culture methods and stem cell biology have progressed, the in vitro production of cultured RBCs (cRBCs) has emerged as a viable option to produce cells for transfusion or to carry therapeutic cargoes. RBCs produced in culture can be quality-tested either by xeno-transfusion of human cells in...
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MDPI AG
2019-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/10/1282 |
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| author | Emmanuel N. Olivier Kai Wang Joshua Grossman Nadim Mahmud Eric E. Bouhassira |
| author_facet | Emmanuel N. Olivier Kai Wang Joshua Grossman Nadim Mahmud Eric E. Bouhassira |
| author_sort | Emmanuel N. Olivier |
| collection | DOAJ |
| description | As cell culture methods and stem cell biology have progressed, the in vitro production of cultured RBCs (cRBCs) has emerged as a viable option to produce cells for transfusion or to carry therapeutic cargoes. RBCs produced in culture can be quality-tested either by xeno-transfusion of human cells into immuno-deficient animals, or by transfusion of autologous cells in immuno-competent models. Although murine xeno-transfusion methods have improved, they must be complemented by studies in immuno-competent models. Non-human primates (NHPs) are important pre-clinical, large animal models due to their high biological and developmental similarities with humans, including their comparable hematopoietic and immune systems. Among NHPs, baboons are particularly attractive to validate cRBCs because of the wealth of data available on the characteristics of RBCs in this species that have been generated by past blood transfusion studies. We report here that we have developed a method to produce enucleated cRBCs by differentiation of baboon induced pluripotent stem cells (iPSCs). This method will enable the use of baboons to evaluate therapeutic cRBCs and generate essential pre-clinical data in an immuno-competent, large animal model. Production of the enucleated baboon cRBCs was achieved by adapting the PSC-RED protocol that we previously developed for human cells. Baboon-PSC-RED is an efficient chemically-defined method to differentiate iPSCs into cRBCs that are about 40% to 50% enucleated. PSC-RED is relatively low cost because it requires no albumin and only small amounts of recombinant transferrin. |
| first_indexed | 2024-03-12T20:17:38Z |
| format | Article |
| id | doaj.art-7c0e22c8e58443e5ad26c13c844ed9c5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T20:17:38Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7c0e22c8e58443e5ad26c13c844ed9c52023-08-02T01:13:49ZengMDPI AGCells2073-44092019-10-01810128210.3390/cells8101282cells8101282Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood CellsEmmanuel N. Olivier0Kai Wang1Joshua Grossman2Nadim Mahmud3Eric E. Bouhassira4Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USADivision of Hematology/Oncology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USADepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USAAs cell culture methods and stem cell biology have progressed, the in vitro production of cultured RBCs (cRBCs) has emerged as a viable option to produce cells for transfusion or to carry therapeutic cargoes. RBCs produced in culture can be quality-tested either by xeno-transfusion of human cells into immuno-deficient animals, or by transfusion of autologous cells in immuno-competent models. Although murine xeno-transfusion methods have improved, they must be complemented by studies in immuno-competent models. Non-human primates (NHPs) are important pre-clinical, large animal models due to their high biological and developmental similarities with humans, including their comparable hematopoietic and immune systems. Among NHPs, baboons are particularly attractive to validate cRBCs because of the wealth of data available on the characteristics of RBCs in this species that have been generated by past blood transfusion studies. We report here that we have developed a method to produce enucleated cRBCs by differentiation of baboon induced pluripotent stem cells (iPSCs). This method will enable the use of baboons to evaluate therapeutic cRBCs and generate essential pre-clinical data in an immuno-competent, large animal model. Production of the enucleated baboon cRBCs was achieved by adapting the PSC-RED protocol that we previously developed for human cells. Baboon-PSC-RED is an efficient chemically-defined method to differentiate iPSCs into cRBCs that are about 40% to 50% enucleated. PSC-RED is relatively low cost because it requires no albumin and only small amounts of recombinant transferrin.https://www.mdpi.com/2073-4409/8/10/1282red blood cellsnon-human primatesengineered red blood cellsinduced pluripotent stem cellsenucleationanimal models |
| spellingShingle | Emmanuel N. Olivier Kai Wang Joshua Grossman Nadim Mahmud Eric E. Bouhassira Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells Cells red blood cells non-human primates engineered red blood cells induced pluripotent stem cells enucleation animal models |
| title | Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells |
| title_full | Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells |
| title_fullStr | Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells |
| title_full_unstemmed | Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells |
| title_short | Differentiation of Baboon (<i>Papio anubis</i>) Induced-Pluripotent Stem Cells into Enucleated Red Blood Cells |
| title_sort | differentiation of baboon i papio anubis i induced pluripotent stem cells into enucleated red blood cells |
| topic | red blood cells non-human primates engineered red blood cells induced pluripotent stem cells enucleation animal models |
| url | https://www.mdpi.com/2073-4409/8/10/1282 |
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