Concise Review: Multiple Niches for Hematopoietic Stem Cell Regulations

Oh, Il‐Hoan; Kwon, Kyung-Rim

doi:10.1002/stem.453

Cited by 68 publications

(22 citation statements)

References 54 publications

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“…We first compared the expression levels of Jagged and CXCL-12, the two cross-talk molecules known to play major roles in supporting HSCs both under in-vivo and in-vitro conditions [6, 13]. As shown in Fig 2A and 2B, each independent line of MSCs cultured under stimulatory conditions exhibited higher level expression of CXCL-12 and Jagged-1 than those with non-stimulatory serum, suggesting that these MSCs can show potential differences in their niche cross-talk with HSCs.…”

Section: Resultsmentioning

confidence: 99%

“…In BM, the MSCs comprise both perivascular and endosteal niche [6]; a subset of mesenchymal stromal cells (MSCs) that retain colony-forming potential (CFU-F) and self-renewal ability could reconstitute both types of niches in the heterologous marrow model [7, 8]. Subsequent studies also showed that BM MSCs expressing nestin [9], leptin-receptor [10], or prx-1 [11] are enriched with CFU-F and play a major role as a niche in BM.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent studies also showed that BM MSCs expressing nestin [9], leptin-receptor [10], or prx-1 [11] are enriched with CFU-F and play a major role as a niche in BM. These niche cells express various types of growth factors or ligands such as Jagged-1[12, 13] or CXCL-12 [11, 14] to regulate self-renewal [12, 15] or quiescence [16, 17] of HSCs [6]. …”

Section: Introductionmentioning

confidence: 99%

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Heterogeneous Niche Activity of Ex-Vivo Expanded MSCs as Factor for Variable Outcomes in Hematopoietic Recovery

et al. 2016

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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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heterogeneous Niche Activity of Ex-Vivo Expanded MSCs as Factor for Variable Outcomes in Hematopoietic Recovery

et al. 2016

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“…Both forms of bone marrow contain extensive numbers of blood vessels and capillaries [81]. Microscopically, osteoblastic niches are spatially separated from vascular niches that provide a systemically enriched oxygen source within the bone marrow [82-85] (Fig. 1).…”

Section: Megakaryocyte and Platelet Biologymentioning

confidence: 99%

Platelets and cancer: a casual or causal relationship: revisited

Menter

Tucker

Kopetz

et al. 2014

Cancer Metastasis Rev

279

256

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Human platelets arise as subcellular fragments of megakaryocytes in bone marrow. The physiologic demand, presence of disease such as cancer, or drug effects can regulate the production circulating platelets. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. The most critical biological platelet response is serving as “First Responders” during the wounding process. The exposure of extracellular matrix proteins and intracellular components occurs after wounding. Numerous platelet receptors recognize matrix proteins that trigger platelet activation, adhesion, aggregation, and stabilization. Once activated, platelets change shape and degranulate to release growth factors and bioactive lipids into the blood stream. This cyclic process recruits and aggregates platelets along with thrombogenesis. This process facilitates wound closure or can recognize circulating pathologic bodies. Cancer cell entry into the blood stream triggers platelet-mediated recognition and is amplified by cell surface receptors, cellular products, extracellular factors, and immune cells. In some cases, these interactions suppress immune recognition and elimination of cancer cells or promote arrest at the endothelium, or entrapment in the microvasculature, and survival. This supports survival and spread of cancer cells and the establishment of secondary lesions to serve as important targets for prevention and therapy.

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“…The bone-forming osteolineage cells results in high local concentrations of Ca 2+ , and the Ca 2+ -sensing receptor promotes the engraftment of HSCs (Adams et al, 2006). In the perivascular niche, endothelial and mesenchymal stem cells, together with sympathetic nerve fibers, modulate HSC behavior (Oh and Kwon, 2010). A major regulator of stem cell function is the Notch receptor system, which ensures a proper balance between stem cells and their progeny by preventing or favoring cell commitment.…”

Section: The Niche: Stem Cells and Supporting Cellsmentioning

confidence: 99%

Cardiac stem cell niches

et al. 2014

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The critical role that stem cell niches have in cardiac homeostasis and myocardial repair following injury is the focus of this review. Cardiac niches represent specialized microdomains where the quiescent and activated state of resident stem cells is regulated. Alterations in niche function with aging and cardiac diseases result in abnormal sites of cardiomyogenesis and inadequate myocyte formation. The relevance of Notch 1 signaling, gap-junction formation, HIF-1α and metabolic state in the regulation of stem cell growth and differentiation within the cardiac niches are discussed.

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Concise Review: Multiple Niches for Hematopoietic Stem Cell Regulations

Cited by 68 publications

References 54 publications

Heterogeneous Niche Activity of Ex-Vivo Expanded MSCs as Factor for Variable Outcomes in Hematopoietic Recovery

Heterogeneous Niche Activity of Ex-Vivo Expanded MSCs as Factor for Variable Outcomes in Hematopoietic Recovery

Platelets and cancer: a casual or causal relationship: revisited

Cardiac stem cell niches

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