Modelos celulares e estratégias biotecnológicas aplicadas à eritropoiese in vitro a partir de células-tronco hematopoiéticas e células-tronco pluripotentes induzidas: uma revisão dos avanços e perspectivas atuais
DOI:
https://doi.org/10.34119/bjhrv8n6-238Keywords:
eritropoiese in vitro, células-tronco hematopoiéticas, células-tronco pluripotentes induzidas, diferenciação eritróide, biotecnologia hematológicaAbstract
A eritropoiese in vitro é um campo emergente da biotecnologia hematológica, com potencial para revolucionar a medicina transfusional e regenerativa. Considerando os desafios na produção de hemácias totalmente funcionais e seguras para uso clínico, atualmente tem uma grande busca para compreender os mecanismos celulares e moleculares que regem a diferenciação eritróide, além da otimização dos protocolos de cultivo. O presente estudo realizou uma revisão, para comparar os avanços recentes na produção de eritrócitos in vitro a partir de células-tronco hematopoiéticas (HSCs) e células-tronco pluripotentes induzidas (iPSCs), destacando suas vantagens, limitações e perspectivas translacionais. Para isso, procedeu-se a uma revisão sistematizada da literatura científica publicada entre 2020 e 2025, por meio das bases PubMed, Scopus, Web of Science, SciELO e Google Scholar; Observa-se que protocolos baseados em HSCs apresentam maior fidelidade fisiológica e taxas de enucleação superiores, enquanto os modelos com iPSCs oferecem maior escalabilidade e compatibilidade genética, embora apresentem em sua maioria, uma maturação incompleta. Dessa forma, conclui-se que a eritropoiese in vitro representa um avanço significativo, mas sua aplicação clínica plena depende da superação de gargalos técnicos e da padronização de processos que garantam qualidade, segurança, reprodutibilidade e viabilidade econômica.
References
AGUIRRE, M. et al. Application of the Yamanaka Transcription Factors Oct4, Sox2, Klf4, and c-Myc from the Laboratory to the Clinic. Stem Cell Research & Therapy, v. 14, art. 146, 2023. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531188/
. Acesso em: 21 jun. 2025.
BOZHILOV, Y. K. et al. In vitro human haematopoietic stem cell expansion and differentiation. Cells, v. 12, n. 6, p. 896, 14 mar. 2023. DOI: 10.3390/cells12060896.
CASTRO-VIÑUELAS, R. et al. Tips and tricks for successfully culturing and adapting human induced pluripotent stem cells. Molecular Therapy: Methods & Clinical Development, v. 23, p. 570-579, dez. 2021.
CHA, HJ. Eritropoiese: perspectivas genômicas. Exp Mol Med 56 , 2099–2104 (2024). https://doi.org/10.1038/s12276-024-01311-1 Disponível em: https://www.nature.com/articles/s12276-024-01311-1
. Acesso em: 15 jul. 2025.
CERNECKIS, J. et al. Induced pluripotent stem cells (iPSCs). Signal Transduction and Targeted Therapy, v. 9, art. 139, 2024. Disponível em: https://www.nature.com/articles/s41392-024-01809-0.
CHO, Y. K. et al. In vitro erythrocyte production using human-induced pluripotent stem cells: determining the best hematopoietic stem cell sources. Stem Cell Research & Therapy, v. 14, art. 106, 26 abr. 2023. DOI: 10.1186/s13287-023-03305-8.
CHUKWUEMEKA, C. G. et al. In vitro erythropoiesis: the emerging potential of induced pluripotent stem cells (iPSCs). Blood Science, v. 7, n. 1, e00215, 2024. DOI: 10.1097/BS9.0000000000000215.
CUESTA-GÓMEZ, N. et al. Suspension culture improves iPSC expansion and quality control for human peripheral blood mononuclear cell-derived iPSCs. Stem Cell Research & Therapy, v. 14, art. 204, 2023. Disponível em: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03382-9
.
DI BUDUO, C. A. et al. In vitro studies of human erythropoiesis using a 3D silk-based bone marrow model that generates erythroblastic islands. Blood Advances, v. 9, n. 9, p. 2192-2206, fev. 2025. DOI: 10.1182/bloodadvances.2024014905.
DOYLE, J. et al. Physiology, Carbon Dioxide Transport. Treasure Island (FL): StatPearls Publishing, 2023. Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK532988/. Acesso em: 12 jun. 2025.
EBRAHIMI, M. et al. Differentiation of human induced pluripotent stem cells into erythroid cells. Stem Cell Research & Therapy, v. 11, art. 483, 16 nov. 2020. DOI: 10.1186/s13287-020-01998-9.
GUNAWARDENA, N.; CHOU, S. T. Generation of red blood cells from induced pluripotent stem cells. Current Opinion in Hematology, v. 31, n. 3, p. 115-121, fev. 2024. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC10959681/
. Acesso em: 12 ago. 2025.
HESHUSIUS, S. et al. Large-scale in vitro production of red blood cells from hematopoietic stem and progenitor cells. Stem Cell Research, v. 39, art. 101541, 2019.
JIANG, J. H. et al. Immune cells and RBCs derived from human induced pluripotent stem cells: method, progress, prospective challenges. Frontiers in Cell and Developmental Biology, v. 11, art. 1327466, 2024. DOI: 10.3389/fcell.2023.1327466. Disponível em: https://doi.org/10.3389/fcell.2023.1327466
. Acesso em: 20 set. 2025.
JU, H. et al. Progresses in overcoming the limitations of in vitro red blood cell manufacturing. Frontiers in Hematology, v. 4, art. 1373408, 2024.
KWEON, S. et al. Current status of red blood cell manufacturing in 3D culture. Blood Research, v. 58, n. 2, p. 68-78, 2023.
LEE, S. J. et al. Generation of red blood cells from human pluripotent stem cells. Cells, v. 12, n. 11, p. 1554, 2023.
LOURENÇO, C. et al. Biological importance of OCT transcription factors in reprogramming somatic cells to induced pluripotent stem cells. Experimental & Molecular Medicine, v. 53, art. 548–557, 2021.
MENÉNDEZ-GONZÁLEZ, J. B. et al. Hematopoietic stem cell mobilization: current collection methods and technologies for transplantation. Frontiers in Cell and Developmental Biology, v. 9, art. 688214, 2021. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663585/
. Acesso em: 19 ago. 2025.
PARK, Y. J. et al. Human induced pluripotent stem cell line banking for the production of rare blood type erythrocytes. Journal of Translational Medicine, v. 18, art. 236, 12 jun. 2020.
SCHIPPEL, N.; SHARMA, S. Dynamics of human hematopoietic stem and progenitor cell differentiation to the erythroid lineage. Experimental Hematology, v. 123, p. 1–17, 2023.
TAJER, P. et al. IL3 has a detrimental effect on hematopoietic stem cell self-renewal in transplantation settings. International Journal of Molecular Sciences, v. 23, n. 21, art. 12736, 2022.
TANG, P.; WANG, H. Regulation of erythropoiesis: emerging concepts and therapeutic implications. Journal of Cellular and Molecular Medicine, v. 27, n. 9, p. 1728-1740, 2023.
ȚICHIL, I. et al. A review of key regulators of steady-state and ineffective erythropoiesis. Journal of Clinical Medicine, v. 13, n. 9, art. 2585, 27 abr. 2024. DOI: 10.3390/jcm13092585.
VARGA, E. et al. Large-scale production of transfusion-ready red blood cells from induced pluripotent stem cells. Advanced Science (Weinheim, Baden-Württemberg, Germany), v. 12, n. 38, e04725, 2025. DOI: 10.1002/advs.202504725.
XIA, X.; LIU, S. H.; ZHOU, H. Structure, dynamics and assembly of the ankyrin complex on human red blood cell membrane. Nature Structural & Molecular Biology, v. 29, p. 698-705, jul. 2022.
YAGI, K. et al. Modeling primitive and definitive erythropoiesis with induced pluripotent stem cells. Blood Advances, v. 8, n. 6, p. 1449-1460, 2024. DOI: 10.1182/bloodadvances.2023005147.
ZHANG, X. et al. Red blood cells in biology and translational medicine. Frontiers in Physiology, v. 15, p. 1145432, 2024.
ZOPF, C. et al. A broad diversity in oxygen affinity to haemoglobin. Scientific Reports, v. 10, art. 73560, 2020.
