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In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment

Hemophilia is a genetic disorder linked to the sex chromosomes, resulting in impaired blood clotting due to insufficient intrinsic coagulation factors. There are approximately one million individuals worldwide with hemophilia, with hemophilia A being the most prevalent form. The current treatment fo...

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Autores principales: Kao, Yung-Tsung, Yen, Chih-Ching, Fan, Hueng-Chuen, Chen, Jen-Kun, Chen, Ming-Shan, Lan, Ying-Wei, Yang, Shang-Hsun, Chen, Chuan-Mu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670993/
https://www.ncbi.nlm.nih.gov/pubmed/38003601
http://dx.doi.org/10.3390/ijms242216411
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author Kao, Yung-Tsung
Yen, Chih-Ching
Fan, Hueng-Chuen
Chen, Jen-Kun
Chen, Ming-Shan
Lan, Ying-Wei
Yang, Shang-Hsun
Chen, Chuan-Mu
author_facet Kao, Yung-Tsung
Yen, Chih-Ching
Fan, Hueng-Chuen
Chen, Jen-Kun
Chen, Ming-Shan
Lan, Ying-Wei
Yang, Shang-Hsun
Chen, Chuan-Mu
author_sort Kao, Yung-Tsung
collection PubMed
description Hemophilia is a genetic disorder linked to the sex chromosomes, resulting in impaired blood clotting due to insufficient intrinsic coagulation factors. There are approximately one million individuals worldwide with hemophilia, with hemophilia A being the most prevalent form. The current treatment for hemophilia A involves the administration of clotting factor VIII (FVIII) through regular and costly injections, which only provide temporary relief and pose inconveniences to patients. In utero transplantation (IUT) is an innovative method for addressing genetic disorders, taking advantage of the underdeveloped immune system of the fetus. This allows mesenchymal stromal cells to play a role in fetal development and potentially correct genetic abnormalities. The objective of this study was to assess the potential recovery of coagulation disorders in FVIII knockout hemophilia A mice through the administration of human amniotic fluid mesenchymal stromal cells (hAFMSCs) via IUT at the D14.5 fetal stage. The findings revealed that the transplanted human cells exhibited fusion with the recipient liver, with a ratio of approximately one human cell per 10,000 mouse cells and produced human FVIII protein in the livers of IUT-treated mice. Hemophilia A pups born to IUT recipients demonstrated substantial improvement in their coagulation issues from birth throughout the growth period of up to 12 weeks of age. Moreover, FVIII activity reached its peak at 6 weeks of age, while the levels of FVIII inhibitors remained relatively low during the 12-week testing period in mice with hemophilia. In conclusion, the results indicated that prenatal intrahepatic therapy using hAFMSCs has the potential to improve clotting issues in FVIII knockout mice, suggesting it as a potential clinical treatment for individuals with hemophilia A.
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spelling pubmed-106709932023-11-16 In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment Kao, Yung-Tsung Yen, Chih-Ching Fan, Hueng-Chuen Chen, Jen-Kun Chen, Ming-Shan Lan, Ying-Wei Yang, Shang-Hsun Chen, Chuan-Mu Int J Mol Sci Article Hemophilia is a genetic disorder linked to the sex chromosomes, resulting in impaired blood clotting due to insufficient intrinsic coagulation factors. There are approximately one million individuals worldwide with hemophilia, with hemophilia A being the most prevalent form. The current treatment for hemophilia A involves the administration of clotting factor VIII (FVIII) through regular and costly injections, which only provide temporary relief and pose inconveniences to patients. In utero transplantation (IUT) is an innovative method for addressing genetic disorders, taking advantage of the underdeveloped immune system of the fetus. This allows mesenchymal stromal cells to play a role in fetal development and potentially correct genetic abnormalities. The objective of this study was to assess the potential recovery of coagulation disorders in FVIII knockout hemophilia A mice through the administration of human amniotic fluid mesenchymal stromal cells (hAFMSCs) via IUT at the D14.5 fetal stage. The findings revealed that the transplanted human cells exhibited fusion with the recipient liver, with a ratio of approximately one human cell per 10,000 mouse cells and produced human FVIII protein in the livers of IUT-treated mice. Hemophilia A pups born to IUT recipients demonstrated substantial improvement in their coagulation issues from birth throughout the growth period of up to 12 weeks of age. Moreover, FVIII activity reached its peak at 6 weeks of age, while the levels of FVIII inhibitors remained relatively low during the 12-week testing period in mice with hemophilia. In conclusion, the results indicated that prenatal intrahepatic therapy using hAFMSCs has the potential to improve clotting issues in FVIII knockout mice, suggesting it as a potential clinical treatment for individuals with hemophilia A. MDPI 2023-11-16 /pmc/articles/PMC10670993/ /pubmed/38003601 http://dx.doi.org/10.3390/ijms242216411 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kao, Yung-Tsung
Yen, Chih-Ching
Fan, Hueng-Chuen
Chen, Jen-Kun
Chen, Ming-Shan
Lan, Ying-Wei
Yang, Shang-Hsun
Chen, Chuan-Mu
In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment
title In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment
title_full In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment
title_fullStr In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment
title_full_unstemmed In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment
title_short In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment
title_sort in utero cell treatment of hemophilia a mice via human amniotic fluid mesenchymal stromal cell engraftment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670993/
https://www.ncbi.nlm.nih.gov/pubmed/38003601
http://dx.doi.org/10.3390/ijms242216411
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