Journal article
Chemically defined cytokine-free expansion of human haematopoietic stem cells
- Abstract:
- Haematopoietic stem cells (HSCs) are a rare cell type that reconstitute the entire blood and immune systems after transplantation and can be used as a curative cell therapy for a variety of haematological diseases1,2. However, the low number of HSCs in the body makes both biological analyses and clinical application difficult, and the limited extent to which human HSCs can be expanded ex vivo remains a substantial barrier to the wider and safer therapeutic use of HSC transplantation3. Although various reagents have been tested in attempts to stimulate the expansion of human HSCs, cytokines have long been thought to be essential for supporting HSCs ex vivo4. Here we report the establishment of a culture system that allows the long-term ex vivo expansion of human HSCs, achieved through the complete replacement of exogenous cytokines and albumin with chemical agonists and a caprolactam-based polymer. A phosphoinositide 3-kinase activator, in combination with a thrombopoietin-receptor agonist and the pyrimidoindole derivative UM171, were sufficient to stimulate the expansion of umbilical cord blood HSCs that are capable of serial engraftment in xenotransplantation assays. Ex vivo HSC expansion was further supported by split-clone transplantation assays and single-cell RNA-sequencing analysis. Our chemically defined expansion culture system will help to advance clinical HSC therapies.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Accepted manuscript, pdf, 9.4MB, Terms of use)
-
(Preview, Supplementary materials, pdf, 20.7MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41586-023-05739-9
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature More from this journal
- Volume:
- 615
- Issue:
- 7950
- Pages:
- 127-133
- Publication date:
- 2023-02-22
- Acceptance date:
- 2023-01-18
- DOI:
- EISSN:
-
1476-4687
- ISSN:
-
0028-0836
- Pmid:
-
36813966
- Language:
-
English
- Keywords:
- Pubs id:
-
1332491
- Local pid:
-
pubs:1332491
- Deposit date:
-
2023-04-25
Terms of use
- Copyright holder:
- Sakurai et al.
- Copyright date:
- 2023
- Rights statement:
- Copyright © 2023, The Author(s), under exclusive licence to Springer Nature Limited
- Notes:
- This is the accepted manuscript version of the article. The final version is available from Springer Nature at https://doi.org/10.1038/s41586-023-05739-9
If you are the owner of this record, you can report an update to it here: Report update to this record