Evidence map›Paper›PMID 22155502›Full record

ArticleBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation2012

Natural killer cell differentiation from hematopoietic stem cells: a comparative analysis of heparin- and stromal cell-supported methods.

Steven A Dezell, Yong-Oon Ahn, Jan Spanholtz, Hongbo Wang, Matthew Weeres, Scott Jackson, Sarah Cooley, Harry Dolstra, Jeffrey S Miller, Michael R Verneris

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. CXCR4 coordinates adhesion, migration, and development of human NK cells.bioRxiv : the preprint server for biology · 2026
    Article
  3. Review
  4. Suppression of CD56Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  5. Review
  6. Anti-NKG2C/IL-15/anti-CD33 killer engager directs primary and iPSC-derived NKG2CMolecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  7. Article
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  10. Review
  11. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Steven A DezellDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Yong-Oon Ahn
Jan Spanholtz
Hongbo Wang
Matthew Weeres
Scott Jackson
Sarah Cooley
Harry Dolstra
Jeffrey S Miller
Michael R Verneris
University of Minnesota · USRadboud University Medical Center · NL

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
NK Cell Differentiation from Stem CellsR01HL055417 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MILLER, JEFFREY S. · 2000 to 2010
$3.2M
NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA65493NHLBI NIH HHS R01 HL055417NHLBI NIH HHS R01 HL55417PHS HHS P01 067493PHS HHS P01 111412
6 · The paper itself

Abstract

Natural killer (NK) cells differentiated from hematopoietic stem cells (HSCs) may have significant clinical benefits over NK cells from adult donors, including the ability to choose alloreactive donors and potentially more robust in vivo expansion. Stromal-based methods have been used to study the differentiation of NK cells from HSCs. Stroma and cytokines support NK cell differentiation, but may face considerable regulatory hurdles. A recently reported clinical-grade, heparin-based method could serve as an alternative. How the stromal-based and heparin-based approaches compare in terms of NK cell generating efficiency or function is unknown. We show that compared with heparin-based cultures, stroma significantly increases the yield of HSC-derived NK cells by differentiating less-committed progenitors into the NK lineage. NK cells generated by both approaches were similar for most NK-activating and -inhibiting receptors. Although both approaches resulted in a phenotype consistent with CD56(bright) stage IV NK cells, heparin-based cultures favored the development of CD56(+)CD16(+) cells, whereas stroma produced more NK cell immunoglobulin-like receptor-expressing NK cells, both of which are markers of terminal maturation. At day 21, stromal-based cultures demonstrated significantly more IL-22 production, and both methods yielded similar amounts of IFN-γ production and cytotoxicity by day 35. These findings suggest that heparin-based cultures are an effective replacement for stroma and may facilitate clinical trials testing HSC-derived NK cells.

Indexed as

Antigens, CD34BiomarkersCD56 AntigenCell Culture TechniquesCell DifferentiationCell ProliferationFemaleFetal BloodHematopoietic Stem CellsHeparinHumansInterferon-gammaInterleukin-22InterleukinsKiller Cells, NaturalReceptors, KIRAntigens, CD34BiomarkersCD56 AntigenHeparinInterferon-gammaInterleukin-22InterleukinsReceptors, KIR

Identifiers

PMID22155502
PMCPMC3303970
OpenAlexW2168489363

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.