Reconstruction of bone marrow microenvironment for expansion of hematopoietic stem cells by a histone deacetylase inhibitor

Ex vivo expansion of hematopoietic stem cells (HSCs) is an approach for overcoming cell insufficiency for umbilical cord blood transplantation. It was suggested that in common ex vivo cultures, the stemness specificity of HSCs is rapidly reducing due to DNA hypermethylation. Here, Nicotinamide (NAM)...

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Bibliographic Details
Published in:Cytotechnology (Dordrecht) 2023-06, Vol.75 (3), p.195-206
Main Authors: Askari, Maryam Haj Ali, Shahabi, Majid, Kojabad, Amir Asri, Zarif, Mahin Nikougoftar
Format: Article
Language:English
Subjects:
Biochemistry
Biomedicine
Biotechnology
Bone marrow
CD34 antigen
Cell division
Cell proliferation
Chemistry
Chemistry and Materials Science
Collagen
Cord blood
Cytokines
Cytology
DNA methyltransferase
Families & family life
Flow cytometry
Gene expression
Granulocytes
Hematopoietic stem cells
Histone deacetylase
Histone methyltransferase
HOXB4 protein
Microenvironments
Nicotinamide
Scanning electron microscopy
Stem cells
Thermal cycling
Transplantation
Transplants & implants
Umbilical cord
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Summary:Ex vivo expansion of hematopoietic stem cells (HSCs) is an approach for overcoming cell insufficiency for umbilical cord blood transplantation. It was suggested that in common ex vivo cultures, the stemness specificity of HSCs is rapidly reducing due to DNA hypermethylation. Here, Nicotinamide (NAM), a DNA methyltransferase and histone deacetylase inhibitor, is used with a bioengineered Bone Marrow-like niche (BLN) for HSC ex vivo expansion. The CFSE cell proliferation assay was used for tracking HSCs division. qRT-PCR was conducted to assay the HOXB4 mRNA expression levels. The morphology of BLN-cultured cells was analyzed using scanning electron microscopy (SEM). NAM boosted the induction of HSC proliferation in the BLN group compared to the control group. In addition, the ability of HSCs to colonize was more significant in the BLN group than in the control group. Our data suggest that the presence of NAM in bioengineered niches promotes HSC proliferation. The presented approach showed that small molecules could be used in the clinical setting to overcome the limited number of CD34 + cells in cord blood units.
ISSN:0920-9069
1573-0778
DOI:10.1007/s10616-022-00564-w