scholarly journals Effects of adipose-derived stromal cells and endothelial progenitor cells on adipose transplant survival and angiogenesis

2020 ◽  
Author(s):  
Xian Zhao ◽  
Fengshan Gan ◽  
Liu Liu ◽  
Qingzhu Zhou ◽  
Wenli Huang ◽  
...  

Abstract Background: A paracrine mechanism is thought to mediate the proangiogenic capacity of adipose-derived stromal/stem cells (ASCs). However, the precise mechanism by which ASCs promote the formation of blood vessels by endothelial progenitor cells (EPCs) is unclear.Methods: We cocultured ASCs with EPCs at various concentrations to study the effects on angiogenesis. The supernatant from cultured ASCs was cocultured with EPCs to evaluate the effects on the expression of vascular endothelial markers in EPCs, as well as capacity for migration and invasion. We then mixed ASCs with EPCs and transplanted them with adipose tissue into New Zealand white rabbits to evaluate the effects on angiogenesis in adipose tissue grafts.Results: As the relative abundance of ASCs cocultured with EPCs increased, the rate of angiogenesis among EPCs decreased. The supernatant from ASC cultures increased the migration and invasion of EPCs and upregulated the expression of vascular endothelial markers in EPCs. In vivo, ASCs promoted the production of blood vessels by EPCs.Conclusions: ASCs are not recruited as structural components of blood vessels but do appear to regulate endothelial progenitor-mediated angiogenesis. The results obtained show that ASC paracrine signaling promotes the formation of blood vessels by EPCs. ASC paracrine signaling appears to promote angiogenesis by increasing the migration and invasion of EPCs and simultaneously upregulating the expression of vascular endothelial markers in EPCs. The results of in vivo experiments showed that ASCs promote the formation of blood vessels in EPC cultures.

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261498
Author(s):  
Fengshan Gan ◽  
Liu Liu ◽  
Qingzhu Zhou ◽  
Wenli Huang ◽  
Xinwei Huang ◽  
...  

Background A paracrine mechanism is thought to mediate the proangiogenic capacity of adipose-derived stromal/stem cells (ASCs). However, the precise mechanism by which ASCs promote the formation of blood vessels by endothelial progenitor cells (EPCs) is unclear. Methods The EPCs-ASCs cocultures prepared in different ratios were subjected to tube formations assay to verify whether ASCs could directly participate in the tube genesis. The supernatant from cultured ASCs was used to stimulate EPCs to evaluate the effects on the angiogenic property of EPCs, as well as capacity for migration and invasion. A coculture model with transwell chamber were used to explore the regulation of angiogenesis markers expression in EPCs by ASCs. We then mixed ASCs with EPCs and transplanted them with adipose tissue into nude mice to evaluate the effects on angiogenesis in adipose tissue grafts. Results In the EPCs-ASCs cocultures, the tube formation was significantly decreased as the relative abundance of ASCs increased, while the ASCs was found to migrate and integrated into the agglomerates formed by EPCs. The supernatant from ASCs cultures promoted the migration and invasion of EPCs and the ability to form capillary-like structures. The expression of multiple angiogenesis markers in EPCs were significantly increased when cocultured with ASCs. In vivo, ASCs combined with EPC promoted vascularization in the fat transplant. Immunofluorescence straining of Edu and CD31 indicated that the Edu labeled EPC did not directly participate in the vascularization inside the fat tissue. Conclusions ADSC can participate in the tube formation of EPC although it cannot form canonical capillary structures. Meanwhile, Soluble factors secreted by ASCs promotes the angiogenic potential of EPCs. ASCs paracrine signaling appears to promote angiogenesis by increasing the migration and invasion of EPCs and simultaneously upregulating the expression of angiogenesis markers in EPCs. The results of in vivo experiments showed that ASCs combined with EPCs significantly promote the formation of blood vessels in the fat implant. Remarkably, EPCs may promote angiogenesis by paracrine regulation of endogenous endothelial cells (ECs) rather than direct participation in the formation of blood vessels.


2016 ◽  
Author(s):  
Rokhsareh Rohban ◽  
Nathalie Etchart ◽  
Thomas R. Pieber

AbstractIt has been believed that de novo vessel formation (neo-vasculogenesis) can be induced by co-transplantation of pericytes or mesenchymal stem/progenitor cells (MSPC) with endothelial cells or endothelial colony-forming cells (ECFC). The requirement for co-transplantation of two adult progenitor cells is one factor that can potentially complicate the process of therapeutic vasculogenesis which hampers the development of strategies for therapeutic intervention referred to as ‘regenerative medicine’. Here we employed a novel strategy for therapeutic vessel development by transplanting endothelial colony forming progenitor cells solely to immune compromised mice and detect vessel formation capacity of single ECFC transplants compared to ECFC/MSPC co-transplants. We applied umbilical cord derived and bone marrow derived-MSPC and umbilical cord derived ECFC with different total cell number for subcutaneous transplantation in matrix composites either alone or mixed at a ratio of 1:5 subcutaneously into immune deficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ; NSG mice. Implants were harvested one day, one, two, eight and 24 weeks after transplantation for detecting the state of vessel formation and stability of the transplants by histological assessments. Additionally, endothelial progenitor cells derived from various human tissues such as umbilical cord blood, peripheral blood and white adipose tissue were used to assess their potential for vessel formation in vivo.Results confirmed that single transplantation of ECFCs with a higher cell number and later in the time course after transplantation is as efficient as co-transplantation of ECFC with MSPC at forming stable-perfused human vessels. Amongst ECFCs isolated from different human sources, white adipose tissue derived ECFC are most potent in forming neo-vessels (micro-vessels) in vivo, thus WAT-ECFC could be an optimal cell for vasculogenesis regenerative application.Co-transplantation of ECFC and MSPC with the defined 5:1 ratio or sole ECFC with a higher cell dosage was essential for vessel generation in vivo.


Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1302-1305 ◽  
Author(s):  
Patrick Au ◽  
Laurence M. Daheron ◽  
Dan G. Duda ◽  
Kenneth S. Cohen ◽  
James A. Tyrrell ◽  
...  

Abstract Tissue engineering requires formation of a de novo stable vascular network. Because of their ability to proliferate, differentiate into endothelial cells, and form new vessels, blood-derived endothelial progenitor cells (EPCs) are attractive source of cells for use in engineering blood vessels. However, the durability and function of EPC-derived vessels implanted in vivo are unclear. To this end, we directly compared formation and functions of tissue-engineered blood vessels generated by peripheral blood– and umbilical cord blood–derived EPCs in a model of in vivo vasculogenesis. We found that adult peripheral blood EPCs form blood vessels that are unstable and regress within 3 weeks. In contrast, umbilical cord blood EPCs form normal-functioning blood vessels that last for more than 4 months. These vessels exhibit normal blood flow, perm-selectivity to macromolecules, and induction of leukocyte-endothelial interactions in response to cytokine activation similar to normal vessels. Thus, umbilical cord blood EPCs hold great therapeutic potential, and their use should be pursued for vascular engineering.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Kourek ◽  
E Karatzanos ◽  
D Delis ◽  
M Alshamari ◽  
V Linardatou ◽  
...  

Abstract Background Chronic heart failure (CHF) remains a leading cause of morbidity and mortality and it is characterized by vascular endothelial dysfunction. During the last decades, endothelial progenitor cells (EPCs) are being used as an index of the endothelium restoration potential, therefore reflecting the vascular endothelial function. Exercise training has been shown to stimulate the mobilization of EPCs at rest in CHF patients. However, the effect of exercise training on the acute respond of EPCs after maximum exercise in CHF patients remains unknown. Purpose The purpose of the study was to assess the effect of a cardiac rehabilitation (CR) program on the acute respond of EPCs after maximum exercise in patients with CHF. Methods Forty-four consecutive patients (35 males) with stable CHF [mean±SD, Age (years): 56±10, BMI (kg/m2): 28.7±5.2, EF (%): 33±8, Peak VO2 (ml/kg/min): 18.4±4.4, Peak work rate (watts): 101±39] enrolled a 36-session CR program based on high-intensity interval exercise training. All patients underwent an initial symptom limited maximal cardiopulmonary exercise testing (CPET) on an ergometer before the CR program and a final maximal CPET after the CR program. Venous blood was drawn before and after each CPET. Five circulating endothelial populations were identified and quantified by flow cytometry; CD34+/CD45-/CD133+, CD34+/CD45-/CD133+/VEGFR2, CD34+/CD133+/VEGFR2, CD34+/CD45-/CD133- and CD34+/CD45-/CD133-/VEGFR2. EPCs values are expressed as cells/million enucleated cells in medians (25th-75th percentiles). Results The acute mobilization of EPCs after the final CPET was higher than after the initial CPET in 4 out of 5 circulating endothelial populations. Most specifically, difference of the acute mobilization of CD34+/CD45-/CD133+ cells [initial CPET: 25 (15–46) vs final CPET: 49 (26–71), p=0.002], CD34+/CD45-/CD133+/VEGFR2 cells [initial CPET: 3 (2–5) vs final CPET: 8 (5–12), p<0.001], CD34+/CD45-/CD133- cells [initial CPET: 129 (52–338) vs final CPET: 250 (129–518), p=0.03] and CD34+/CD45-/CD133-/VEGFR2 cells [initial CPET: 2 (1–4) vs final CPET: 6 (3–9), p<0.001] increased after the final CPET. The acute mobilization of CD34+/CD133+/VEGFR2 cells [initial CPET: 3 (−1–7) vs final CPET: 5 (0–15), p=0.441] did not differ between the 2 CPETS. Conclusion A 36-session cardiac rehabilitation program increases the acute respond of endothelial progenitor cells after maximum cardiopulmonary exercise training in patients with chronic heart failure, therefore indicating the beneficial effect of exercise training on the vascular endothelial function. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project


2016 ◽  
Vol 130 (22) ◽  
pp. 2029-2042 ◽  
Author(s):  
Shengyuan Luo ◽  
Wenhao Xia ◽  
Cong Chen ◽  
Eric A. Robinson ◽  
Jun Tao

The discovery of endothelial progenitor cells (EPCs), a group of cells that play important roles in angiogenesis and the maintenance of vascular endothelial integrity, has led to considerable improvements in our understanding of the circulatory system and the regulatory mechanisms of vascular homoeostasis. Despite lingering disputes over where EPCs actually originate and how they facilitate angiogenesis, extensive research in the past decade has brought about significant advancements in this field of research, establishing EPCs as an essential element in the pathogenesis of various diseases. EPC and hypertensive disorders, especially essential hypertension (EH, also known as primary hypertension), represent one of the most appealing branches in this area of research. Chronic hypertension remains a major threat to public health, and the exact pathologic mechanisms of EH have never been fully elucidated. Is there a relationship between EPC and hypertension? If so, what is the nature of such relationship–is it mediated by blood pressure alterations, or other factors that lie in between? How can our current knowledge about EPCs be utilized to advance the prevention and clinical management of hypertension? In this review, we set out to answer these questions by summarizing the current concepts about EPC pathophysiology in the context of hypertension, while attempting to point out directions for future research on this subject.


PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20790 ◽  
Author(s):  
Jun Chen ◽  
Zhen-Yu Jia ◽  
Zhan-Long Ma ◽  
Yuan-Yuan Wang ◽  
Gao-Jun Teng

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