Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders
Inherited blood disorders comprise a large spectrum of diseases due to germline mutations in genes with key function in the hematopoietic system; they include immunodeficiencies, anemia or metabolic diseases. For most of them the only curative treatment is bone marrow transplantation, a procedure as...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/3/557 |
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| author | Ilaria Rao Laura Crisafulli Marianna Paulis Francesca Ficara |
| author_facet | Ilaria Rao Laura Crisafulli Marianna Paulis Francesca Ficara |
| author_sort | Ilaria Rao |
| collection | DOAJ |
| description | Inherited blood disorders comprise a large spectrum of diseases due to germline mutations in genes with key function in the hematopoietic system; they include immunodeficiencies, anemia or metabolic diseases. For most of them the only curative treatment is bone marrow transplantation, a procedure associated to severe complications; other therapies include red blood cell and platelet transfusions, which are dependent on donor availability. An alternative option is gene therapy, in which the wild-type form of the mutated gene is delivered into autologous hematopoietic stem cells using viral vectors. A more recent therapeutic perspective is gene correction through CRISPR/Cas9-mediated gene editing, that overcomes safety concerns due to insertional mutagenesis and allows correction of base substitutions in large size genes difficult to incorporate into vectors. However, applying this technique to genomic disorders caused by large gene deletions is challenging. Chromosomal transplantation has been proposed as a solution, using a universal source of wild-type chromosomes as donor, and induced pluripotent stem cells (iPSCs) as acceptor. One of the obstacles to be addressed for translating PSC research into clinical practice is the still unsatisfactory differentiation into transplantable hematopoietic stem or mature cells. We provide an overview of the recent progresses in this field and discuss challenges and potential of iPSC-based therapies for the treatment of inherited blood disorders. |
| first_indexed | 2024-03-10T00:02:26Z |
| format | Article |
| id | doaj.art-85aecaec6cff4640b98ae48f8c4f589a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:02:26Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-85aecaec6cff4640b98ae48f8c4f589a2023-11-23T16:13:56ZengMDPI AGCells2073-44092022-02-0111355710.3390/cells11030557Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood DisordersIlaria Rao0Laura Crisafulli1Marianna Paulis2Francesca Ficara3IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyIRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, ItalyInherited blood disorders comprise a large spectrum of diseases due to germline mutations in genes with key function in the hematopoietic system; they include immunodeficiencies, anemia or metabolic diseases. For most of them the only curative treatment is bone marrow transplantation, a procedure associated to severe complications; other therapies include red blood cell and platelet transfusions, which are dependent on donor availability. An alternative option is gene therapy, in which the wild-type form of the mutated gene is delivered into autologous hematopoietic stem cells using viral vectors. A more recent therapeutic perspective is gene correction through CRISPR/Cas9-mediated gene editing, that overcomes safety concerns due to insertional mutagenesis and allows correction of base substitutions in large size genes difficult to incorporate into vectors. However, applying this technique to genomic disorders caused by large gene deletions is challenging. Chromosomal transplantation has been proposed as a solution, using a universal source of wild-type chromosomes as donor, and induced pluripotent stem cells (iPSCs) as acceptor. One of the obstacles to be addressed for translating PSC research into clinical practice is the still unsatisfactory differentiation into transplantable hematopoietic stem or mature cells. We provide an overview of the recent progresses in this field and discuss challenges and potential of iPSC-based therapies for the treatment of inherited blood disorders.https://www.mdpi.com/2073-4409/11/3/557pluripotent stem celliPSChematopoietic stem cellhematopoiesisdifferentiationinherited blood disorders |
| spellingShingle | Ilaria Rao Laura Crisafulli Marianna Paulis Francesca Ficara Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders Cells pluripotent stem cell iPSC hematopoietic stem cell hematopoiesis differentiation inherited blood disorders |
| title | Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders |
| title_full | Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders |
| title_fullStr | Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders |
| title_full_unstemmed | Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders |
| title_short | Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders |
| title_sort | hematopoietic cells from pluripotent stem cells hope and promise for the treatment of inherited blood disorders |
| topic | pluripotent stem cell iPSC hematopoietic stem cell hematopoiesis differentiation inherited blood disorders |
| url | https://www.mdpi.com/2073-4409/11/3/557 |
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