ArticlePloS one2016
Heterogeneous Niche Activity of Ex-Vivo Expanded MSCs as Factor for Variable Outcomes in Hematopoietic Recovery.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Surgical margins after partial nephrectomy as prognostic factor for the risk of local recurrence in pT1 RCC: a systematic review and narrative synthesis.World journal of urology · 2022Pooled it
- Conserved stromal EMT program controls regenerative capacity of mesenchymal stromal cells across multiple tissues.Science advances · 2026Article
- Antisense Oligonucleotides against Let-7 Enhance the Therapeutic Potential of Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Article
- How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models.World journal of stem cells · 2022Article
- Reversible switching of leukemic cells to a drug-resistant, stem-like subset via IL-4-mediated cross-talk with mesenchymal stroma.Haematologica · 2022Article
- Leukemia-Induced Cellular Senescence and Stemness Alterations in Mesenchymal Stem Cells Are Reversible upon Withdrawal of B-Cell Acute Lymphoblastic Leukemia Cells.International journal of molecular sciences · 2021Article
- Nasal Turbinate Mesenchymal Stromal Cells Preserve Characteristics of Their Neural Crest Origin and Exert Distinct Paracrine Activity.Journal of clinical medicine · 2021Article
- Xeno-Free Condition Enhances Therapeutic Functions of Human Wharton's Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis by Upregulated Indoleamine 2,3-Dioxygenase Activity.Journal of clinical medicine · 2020Article
- Ryk modulates the niche activity of mesenchymal stromal cells by fine-tuning canonical Wnt signaling.Experimental & molecular medicine · 2020Article
- Age-related differences in the bone marrow stem cell niche generate specialized microenvironments for the distinct regulation of normal hematopoietic and leukemia stem cells.Scientific reports · 2019Article
- Shift of EMT gradient in 3D spheroid MSCs for activation of mesenchymal niche function.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ex-vivo expanded mesenchymal stromal cells (MSCs) are increasingly used for paracrine support of hematopoietic stem cell (HSC) regeneration, but inconsistent outcomes have hindered ongoing clinical trials. Here, we show that significant heterogeneity in the niche activity of MSCs is created during their culture in various serum-supplemented media. The MSCs cultured under stimulatory or non-stimulatory culture conditions exhibited differences in colony forming unit-fibroblast contents, expression levels of cross-talk molecules (Jagged-1 and CXCL-12) and their support for HSC self-renewal. Accordingly, the enhancing effects of MSCs on hematopoietic engraftment were only visible when HSCs were co-transplanted with MSCs under stimulatory conditions. Of note, these differences in MSCs and their effects on HSCs were readily reversed by switching the cultures, indicating that the difference in niche activity can be caused by distinct functional state, rather than by clonal heterogeneity. Supporting the findings, transcriptomic analysis showed distinct upstream signaling pathways such as inhibition of P53 and activation of ER-stress response gene ATF4 for MSCs under stimulatory conditions. Taken together, our study shows that the niche activity of MSCs can vary rapidly by the extrinsic cues during culture causing variable outcomes in hematopoietic recoveries, and point to the possibility that MSCs can be pre-screened for more predictable efficacy in various cell therapy trials.
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