Title |
Wnt3a nanodisks promote ex vivo expansion of hematopoietic stem and progenitor cells
|
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Published in |
Journal of Nanobiotechnology, August 2016
|
DOI | 10.1186/s12951-016-0218-5 |
Pubmed ID | |
Authors |
Nahal R. Lalefar, Andrzej Witkowski, Jens B. Simonsen, Robert O. Ryan |
Abstract |
Wnt proteins modulate development, stem cell fate and cancer through interactions with cell surface receptors. Wnts are cysteine-rich, glycosylated, lipid modified, two domain proteins that are prone to aggregation. The culprit responsible for this behavior is a covalently bound palmitoleoyl moiety in the N-terminal domain. By combining murine Wnt3a with phospholipid and apolipoprotein A-I, ternary complexes termed nanodisks (ND) were generated. ND-associated Wnt3a is soluble in the absence of detergent micelles and gel filtration chromatography revealed that Wnt3a co-elutes with ND. In signaling assays, Wnt3a ND induced β-catenin stabilization in mouse fibroblasts as well as hematopoietic stem and progenitor cells (HSPC). Prolonged exposure of HSPC to Wnt3a ND stimulated proliferation and expansion of Lin(-) Sca-1(+) c-Kit(+) cells. Surprisingly, ND lacking Wnt3a contributed to Lin(-) Sca-1(+) c-Kit(+) cell expansion, an effect that was not mediated through β-catenin. The data indicate Wnt3a ND constitute a water-soluble transport vehicle capable of promoting ex vivo expansion of HSPC. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 16 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 3 | 19% |
Student > Master | 2 | 13% |
Student > Bachelor | 2 | 13% |
Professor > Associate Professor | 2 | 13% |
Researcher | 1 | 6% |
Other | 1 | 6% |
Unknown | 5 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 5 | 31% |
Biochemistry, Genetics and Molecular Biology | 3 | 19% |
Computer Science | 1 | 6% |
Physics and Astronomy | 1 | 6% |
Chemistry | 1 | 6% |
Other | 0 | 0% |
Unknown | 5 | 31% |