scholarly journals Contribution of Adventitia-Derived Stem and Progenitor Cells to New Vessel Formation in Tumors

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1719
Author(s):  
Berin Upcin ◽  
Erik Henke ◽  
Florian Kleefeldt ◽  
Helene Hoffmann ◽  
Andreas Rosenwald ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Network Formation ◽  
Ex Vivo ◽  
Aortic Ring ◽  
Angiogenesis Inhibitors ◽  
Collagen Gels ◽  
Tumor Vascularization ◽  
Ex Vivo Model ◽  
Vessel Formation ◽  
Stem And Progenitor Cells

Blocking tumor vascularization has not yet come to fruition to the extent it was hoped for, as angiogenesis inhibitors have shown only partial success in the clinic. We hypothesized that under-appreciated vascular wall-resident stem and progenitor cells (VW-SPCs) might be involved in tumor vascularization and influence effectiveness of anti-angiogenic therapy. Indeed, in patient samples, we observed that vascular adventitia-resident CD34+ VW-SPCs are recruited to tumors in situ from co-opted vessels. To elucidate this in detail, we established an ex vivo model using concomitant embedding of multi-cellular tumor spheroids (MCTS) and mouse aortic rings (ARs) into collagen gels, similar to the so-called aortic ring assay (ARA). Moreover, ARA was modified by removing the ARs’ adventitia that harbors VW-SPCs. Thus, this model enabled distinguishing the contribution of VW-SPCs from that of mature endothelial cells (ECs) to new vessel formation. Our results show that the formation of capillary-like sprouts is considerably delayed, and their number and network formation were significantly reduced by removing the adventitia. Substituting iPSC-derived neural spheroids for MCTS resulted in distinct sprouting patterns that were also strongly influenced by the presence or absence of VW-SPCs, also underlying the involvement of these cells in non-pathological vascularization. Our data suggest that more comprehensive approaches are needed in order to block all of the mechanisms contributing to tumor vascularization.

scholarly journals Ex vivo expansion of human hematopoietic stem and progenitor cells

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6083-6090 ◽  
Author(s):  
Ann Dahlberg ◽  
Colleen Delaney ◽  
Irwin D. Bernstein
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Growth Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

AbstractDespite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.

Adhesion to Fibronectin Maintains Regenerative Capacity During Ex Vivo Culture and Transduction of Human Hematopoietic Stem and Progenitor Cells

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4612-4621 ◽  
Author(s):  
M.A. Dao ◽  
K. Hashino ◽  
I. Kato ◽  
J.A. Nolta
Keyword(s):  
Progenitor Cells ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Retroviral Vectors ◽  
Current Data ◽  
Regenerative Capacity ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Ex Vivo Culture

Abstract Recent reports have indicated that there is poor engraftment from hematopoietic stem cells (HSC) that have traversed cell cycle ex vivo. However, inducing cells to cycle in culture is critical to the fields of ex vivo stem cell expansion and retroviral-mediated gene therapy. Through the use of a xenograft model, the current data shows that human hematopoietic stem and progenitor cells can traverse M phase ex vivo, integrate retroviral vectors, engraft, and sustain long-term hematopoiesis only if they have had the opportunity to engage their integrin receptors to fibronectin during the culture period. If cultured in suspension under the same conditions, transduction is undetectable and the long-term multilineage regenerative capacity of the primitive cells is severely diminished.

Clinical-scale validation of a new efficient procedure for cryopreservation of ex vivo expanded cord blood hematopoietic stem and progenitor cells

Cytotherapy ◽  
2016 ◽  
Vol 18 (12) ◽  
pp. 1543-1547 ◽  
Author(s):  
Pascale Duchez ◽  
Laura Rodriguez ◽  
Jean Chevaleyre ◽  
Philippe Brunet De La Grange ◽  
Zoran Ivanovic
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Scale Validation ◽  
Ex Vivo ◽  
Clinical Scale ◽  
Hematopoietic Stem ◽  
Efficient Procedure ◽  
Stem And Progenitor Cells

scholarly journals EFFECTS OF N-ACETYL-CYSTEINE SUPPLEMENTATION ON EX-VIVO CLONOGENICITY AND OXIDATIVE PROFILE OF LINEAGE-COMMITTED HEMATOPOIETIC STEM/PROGENITOR CELLS

2018 ◽  
Vol 80 (3) ◽  
Author(s):  
Chan Chin Yi ◽  
Zariyantey Abd Hamid ◽  
Izatus Shima Taib ◽  
Tan Hui Yee ◽  
Muhd Khairul Akmal Wak Harto ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Ex Vivo ◽  
Oxidative Status ◽  
Oxygen Species ◽  
Hematopoietic Stem ◽  
Colony Forming Units ◽  
Stem And Progenitor Cells ◽  
Acetyl Cysteine ◽  
Antioxidant Supplement ◽  
B Lymphoid

Hematopoietic stem and progenitor cells (HSPCs) are exposed to oxidative damage acquired during ex vivo expansion which affects their therapeutic potency. Efforts to overcome this limitation includes the use of antioxidants. The effects of N-Acetyl-Cysteine (NAC) supplementation for 48 hours on maintenance of ex vivo HSPCs was investigated by examining the cell viability at concentrations of 0.125 µM, 0.25 µM, 0.5 µM, 1.0 µM and 2.0 µM, followed by clonogenicity and oxidative status assessments of lineage-committed progenitors (myeloid, erythroid and pre-B lymphoid) at selected NAC concentrations (0.25 µM, 0.5 µM, 2.0 µM). NAC supplementation significantly (p< 0.05) enhanced viability of HSPC at 0.25 µM, 0.5 µM, 2.0 µM.  The clonogenicity of each progenitor was not affected as no significant changes of Colony Forming Units (CFUs) counts was noted between NAC-supplemented group than control. NAC showed no significant effects on reactive oxygen species (ROS), glutathione (GSH) and superoxide dismutase (SOD) levels of respective progenitors as compared to control. Conclusively, NAC shows potential property as antioxidant supplement for ex vivo maintenance of HSPCs by promoting survivability and maintaining clonogenicity.

scholarly journals Exosomes derived from induced vascular progenitor cells promote angiogenesis in vitro and in an in vivo rat hindlimb ischemia model

2019 ◽  
Vol 317 (4) ◽  
pp. H765-H776 ◽  
Author(s):  
Takerra K. Johnson ◽  
Lina Zhao ◽  
Dihan Zhu ◽  
Yang Wang ◽  
Yan Xiao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Aortic Ring ◽  
Size Exclusion ◽  
Hindlimb Ischemia ◽  
Vascular Progenitor Cells ◽  
Angiogenic Effect

Induced vascular progenitor cells (iVPCs) were created as an ideal cell type for regenerative medicine and have been reported to positively promote collateral blood flow and improve cardiac function in a rat model of myocardial ischemia. Exosomes have emerged as a novel biomedicine that mimics the function of the donor cells. We investigated the angiogenic activity of exosomes from iPVCs (iVPC-Exo) as a cell-free therapeutic approach for ischemia. Exosomes from iVPCs and rat aortic endothelial cells (RAECs) were isolated using a combination of ultrafiltration and size-exclusion chromatography. Nanoparticle tracking analysis revealed that exosome isolates fell within the exosomal diameter (<150 nm). These exosomes contained known markers Alix and TSG101, and their morphology was validated using transmission electron microscopy. When compared with RAECs, iVPCs significantly increased the secretion of exosomes. Cardiac microvascular endothelial cells and aortic ring explants were pretreated with RAEC-Exo or iVPC-Exo, and basal medium was used as a control. iVPC-Exo exerted an in vitro angiogenic effect on the proliferation, tube formation, and migration of endothelial cells and stimulated microvessel sprouting in an ex vivo aortic ring assay. Additionally, iVPC-Exo increased blood perfusion in a hindlimb ischemia model. Proangiogenic proteins (pentraxin-3 and insulin-like growth factor-binding protein-3) and microRNAs (-143-3p, -291b, and -20b-5p) were found to be enriched in iVPC-Exo, which may mediate iVPC-Exo induced vascular growth. Our findings demonstrate that treatment with iVPC-Exo promotes angiogenesis in vitro, ex vivo, and in vivo. Collectively, these findings indicate a novel cell-free approach for therapeutic angiogenesis. NEW & NOTEWORTHY The results of this work demonstrate exosomes as a novel physiological mechanism by which induced vascular progenitor cells exert their angiogenic effect. Moreover, angiogenic cargo of proteins and microRNAs may define the biological contributors in activating endothelial cells to form a new capillary plexus for ischemic vascular diseases. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/angiogenic-exosomes-from-vascular-progenitor-cells/ .

scholarly journals Directed Differentiation of Mobilized Hematopoietic Stem and Progenitor Cells into Functional NK Cells with Enhanced Antitumor Activity

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 811
Author(s):  
Pranav Oberoi ◽  
Kathrina Kamenjarin ◽  
Jose Francisco Villena Ossa ◽  
Barbara Uherek ◽  
Halvard Bönig ◽  
...  
Keyword(s):  
Nk Cells ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Cell Expansion ◽  
Nk Cell ◽  
Ex Vivo ◽  
Feeder Cells ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Stem And Progenitor Cells

Obtaining sufficient numbers of functional natural killer (NK) cells is crucial for the success of NK-cell-based adoptive immunotherapies. While expansion from peripheral blood (PB) is the current method of choice, ex vivo generation of NK cells from hematopoietic stem and progenitor cells (HSCs) may constitute an attractive alternative. Thereby, HSCs mobilized into peripheral blood (PB-CD34+) represent a valuable starting material, but the rather poor and donor-dependent differentiation of isolated PB-CD34+ cells into NK cells observed in earlier studies still represents a major hurdle. Here, we report a refined approach based on ex vivo culture of PB-CD34+ cells with optimized cytokine cocktails that reliably generates functionally mature NK cells, as assessed by analyzing NK-cell-associated surface markers and cytotoxicity. To further enhance NK cell expansion, we generated K562 feeder cells co-expressing 4-1BB ligand and membrane-anchored IL-15 and IL-21. Co-culture of PB-derived NK cells and NK cells that were ex-vivo-differentiated from HSCs with these feeder cells dramatically improved NK cell expansion, and fully compensated for donor-to-donor variability observed during only cytokine-based propagation. Our findings suggest mobilized PB-CD34+ cells expanded and differentiated according to this two-step protocol as a promising source for the generation of allogeneic NK cells for adoptive cancer immunotherapy.

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