Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo

Salter, Alice B.; Meadows, Sarah K.; Muramoto, Garrett G.; Himburg, Heather A.; Doan, Phuong L.; Daher, Pamela; Russell, Lauren; Chen, Benny; Chao, Nelson J.; Chute, John P.

doi:10.1182/blood-2008-06-162941

Cited by 135 publications

(162 citation statements)

References 22 publications

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“…Overall, these results showed that the cells expanded on all extracellular matrix (ECM) were not hematopoietic after 7 days. EPCs characterization and the expression level of CD markers used for characterization in this study were consistent with previous reports of murine EPC features (Salter et al 2009;Siavashi et al in press).…”

Section: Morphological Characteristics Of Epcssupporting

confidence: 80%

“…Moreover, EPCs expanded on all ECMs yielded only CFU-EC after seeding on the methylcellulose medium supplemented with VEGF and GM-CSF, further substantiating that these cells were not from an hematopoietic origin (Salter et al 2009). …”

Section: Discussionmentioning

confidence: 88%

“…An isotype control was used for each assay. To further distinguish the EPCs pre-expanded on fibronectin from hematopoietic progenitor cells, 4 × 10 4 EPCs were plated in the methylcellulose semi-solid medium containing 100 ng/ml VEGF and 5 ng/ml Granulocyte-macrophage colony-stimulating factor (GM-CSF) for two weeks, as described previously (Salter et al 2009). The colonies were finally imaged and counted.…”

Section: Epc Characterizationmentioning

confidence: 99%

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Angiogenic activity of endothelial progenitor cells through angiopoietin-1 and angiopoietin-2

Siavashi

Sariri

Nassiri

et al. 2016

Animal Cells and Systems

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Angiogenesis is a regulated process involving the proliferation, migration, and remodeling of different cell types particularly mature endothelial cells and recently discovered progenitor cells, named as endothelial progenitor cells (EPCs). Up to now, many attempts have been made to understand the dynamic balance of pro-and anti-angiogenic factors on EPCs on different milieu. It has been accepted that Ang-1, -2 and Tie-1, -2 signaling play a key role on angiogenesis pathways in endothelial lineage cells. In the current experiment, the angiogenic/angiomodulatory potency of Ang-1 and -2 was investigated on isolated EPCs. Freshly isolated EPCs were exposed to different concentrations of Ang-1 and -2 (25 and 50 ng/ml) over a course of 7 and 14 days. Corroborating to our results, a superior effect of Ang-1 on angiogenic properties, including an increased concentration of vascular endothelial growth factor, in vitro tubulogenesis, EPC migratory, Tie-2 expression and clonogenicity, was determined. A large amount of positive mature endothelium markers was achieved in EPCs being-exposed to Ang-1 peptide. Nonetheless, the number of CD133 positive cells increased in the presence of Ang-2. Collectively, we conclude that Ang-1 potentially induces functional and mature vascular-like behavior in EPCs more than Ang-2.ARTICLE HISTORY

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Section: Morphological Characteristics Of Epcssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 88%

Section: Epc Characterizationmentioning

confidence: 99%

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Angiogenic activity of endothelial progenitor cells through angiopoietin-1 and angiopoietin-2

Siavashi

Sariri

Nassiri

et al. 2016

Animal Cells and Systems

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“…18 Allogeneic endothelial progenitor cell infusions were also shown to induce hematologic recovery and a quantitative increase in long-term repopulating HSC content compared with control mice following TBIinduced myelosuppression, suggesting that ECs positively regulated HSC reconstitution in vivo. 53 Interestingly, we found that transplanted ECs did not engraft directly in the BM vasculature, but rather engrafted temporarily in the lungs of recipient mice, suggesting that soluble factors were elaborated by infused ECs, which promoted vascular and HSC regeneration. 53 In keeping with these findings, Slayton et al 54 demonstrated that, following BM transplantation, reconstitution of the BM vasculature derives predominantly from host ECs rather than donor-derived endothelial progenitor cells.…”

Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 87%

“…53 Interestingly, we found that transplanted ECs did not engraft directly in the BM vasculature, but rather engrafted temporarily in the lungs of recipient mice, suggesting that soluble factors were elaborated by infused ECs, which promoted vascular and HSC regeneration. 53 In keeping with these findings, Slayton et al 54 demonstrated that, following BM transplantation, reconstitution of the BM vasculature derives predominantly from host ECs rather than donor-derived endothelial progenitor cells.…”

Section: Do Ecs Secrete Soluble Growth Factors That Mediate Hsc Self-mentioning

confidence: 87%

The vascular niche: home for normal and malignant hematopoietic stem cells

2011

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Hematopoietic stem cells (HSCs) are uniquely capable of selfrenewal and provision of all of the mature elements of the blood and immune system throughout the lifetime of an individual. HSC self-renewal is regulated by both intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments or 'niches' wherein HSCs reside. HSCs have been shown to reside in close association with bone marrow (BM) osteoblasts in the endosteal niche and also in proximity to BM sinusoidal vessels. An unresolved question surrounds whether the endosteal and vascular niches provide synchronous or redundant regulation of HSC fate or whether these niches provide wholly unique regulatory functions. Furthermore, while some aspects of the mechanisms through which osteoblasts regulate HSC fate have been defined, the mechanisms through which the vascular niche regulates HSC fate remain obscure. Here, we summarize the anatomic and functional basis supporting the concept of an HSC vascular niche as well as the precise function of endothelial cells, perivascular cells and stromal cells within the niche in regulating HSC fate. Lastly, we will highlight the role of the vascular niche in regulating leukemic stem cell fate in vivo. Leukemia (2012) Concept of the hematopoietic stem cell (HSC) nicheThe concept of an instructive role for the bone marrow (BM) microenvironment in regulating hematopoietic cell fate was introduced at least 50 years ago and has been validated over the past decade. 1-9 It has long been postulated that HSCs reside in specialized niches within the adult BM. [8][9][10][11][12][13][14] In addition to HSCs and their progeny, the BM comprises a rich network of osteoblasts, mesenchymal stem cells (MSCs), neuronal cells, adipocytes, sinusoidal vessels and perivascular reticular cells (Figure 1). Recently, genetic knockout studies have begun to demonstrate the functional role of specific cells within the BM microenvironment in regulating hematopoiesis. [3][4][5]7,[15][16][17][18][19][20] Interestingly, certain niches within the BM may uniquely regulate HSC homeostasis in vivo while other niches may be more relevant to HSC regeneration following injury. However, it remains unknown whether there is meaningful 'cross-talk' between distinct microenvironmental cells in regulating HSC fate in vivo. Interestingly, as early as 1961, Fliedner et al. 9 postulated that the recovery of hematopoiesis in rats following 1000 cGy total body irradiation (TBI) required the recovery of an intact vasculature. Similarly, McClugage et al. 14 used a window chamber to visualize dynamic changes in tibial BM cellularity and architecture in live rabbits. Interestingly, both studies suggested a strong association between vasculogenesis in the BM and the hematopoietic response to stress or injury. 9,14 Role of the BM osteoblast With advances in mouse genetics and microscopy, the function of the BM osteoblast in regulating hematopoiesis and HSC homeostasis has been demonstrated. 4,5,14,[21][22][23][24] Human osteoblasts were shown by Taichma...

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Hydrogels Containing Gradients in Vascular Density Reveal Dose‐Dependent Role of Angiocrine Cues on Stem Cell Behavior

Ngo

Barnhouse

Gilchrist

et al. 2021

Adv Funct Materials

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Biomaterials that replicate patterns of microenvironmental signals from the stem cell niche offer the potential to refine platforms to regulate stem cell behavior. While significant emphasis has been placed on understanding the effects of biophysical and biochemical cues on stem cell fate, vascularderived or angiocrine cues offer an important alternative signaling axis for biomaterial-based stem cell platforms. Elucidating dose-dependent relationships between angiocrine cues and stem cell fate are largely intractable in animal models and 2D cell cultures. In this study, microfluidic mixing devices are leveraged to generate 3D hydrogels containing lateral gradients in vascular density alongside murine hematopoietic stem cells (HSCs). Regional differences in vascular density can be generated via embossed gradients in cell, matrix, or growth factor density. HSCs co-cultured alongside vascular gradients reveal spatial patterns of HSC phenotype in response to angiocrine signals. Notably, decreased Akt signaling in high vessel density regions led to increased expansion of lineage-positive hematopoietic cells. This approach offers a combinatorial tool to rapidly screen a continuum of microenvironments with varying vascular, biophysical, and biochemical cues to reveal the influence of local angiocrine signals on HSC fate.

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Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo

Cited by 135 publications

References 22 publications

Angiogenic activity of endothelial progenitor cells through angiopoietin-1 and angiopoietin-2

Angiogenic activity of endothelial progenitor cells through angiopoietin-1 and angiopoietin-2

The vascular niche: home for normal and malignant hematopoietic stem cells

Hydrogels Containing Gradients in Vascular Density Reveal Dose‐Dependent Role of Angiocrine Cues on Stem Cell Behavior

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