Human multipotent hematopoietic progenitor cell expansion is neither supported in endothelial and endothelial/mesenchymal co-cultures nor in NSG mice

Autor:	Radtke, Stefan, Görgens, André, da Conceição Castro, Symone Vitoriano, Kordelas, Lambros, Köninger, Angela, Dürig, Jan, Möllmann, Michael, Horn, Peter A., Giebel, Bernd
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	Medizin lcsh:Medicine Medizinische Fakultät » Universitätsklinikum Essen » Institut für Transfusionsmedizin Mice SCID Article Immunophenotyping Mice Mice Inbred NOD ddc:61 Animals Humans Cell Lineage ddc:610 lcsh:Science Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Knochenmarktransplantation Haematopoietic stem cells Multipotent Stem Cells lcsh:R Endothelial Cells Cell Differentiation Mesenchymal Stem Cells Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Hämatologie und Stammzelltransplantation Hematopoietic Stem Cells Coculture Techniques Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Frauenheilkunde und Geburtshilfe lcsh:Q Stem-cell niche Biomarkers
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-49221-x
Popis:	Endothelial and mesenchymal stromal cells (ECs/MSCs) are crucial components of hematopoietic bone marrow stem cell niches. Both cell types appear to be required to support the maintenance and expansion of multipotent hematopoietic cells, i.e. hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). With the aim to exploit niche cell properties for experimental and potential clinical applications, we analyzed the potential of primary ECs alone and in combination with MSCs to support the ex vivo expansion/maintenance of human hematopoietic stem and progenitor cells (HSPCs). Even though a massive expansion of total CD34+ HSPCs was observed, none of the tested culture conditions supported the expansion or maintenance of multipotent HSPCs. Instead, mainly lympho-myeloid primed progenitors (LMPPs) were expanded. Similarly, following transplantation into immunocompromised mice the percentage of multipotent HSPCs within the engrafted HSPC population was significantly decreased compared to the original graft. Consistent with the in vitro findings, a bias towards lympho-myeloid lineage potentials was observed. In our conditions, neither classical co-cultures of HSPCs with primary ECs or MSCs, even in combination, nor the xenograft environment in immunocompromised mice efficiently support the expansion of multipotent HSPCs. Instead, enhanced expansion and a consistent bias towards lympho-myeloid committed LMPPs were observed. OA Förderung 2019
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::acf660651b49e5cd4e4b521073026238 http://link.springer.com/article/10.1038/s41598-019-49221-x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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