Fibroblast growth factor and vascular endothelial growth factor play a critical role in endotheliogenesis from human adipose-derived stem cells.

Published on May 1, 2017in Journal of Vascular Surgery3.405
· DOI :10.1016/J.JVS.2016.04.034
Sophia Khan2
Estimated H-index: 2
(Rowan University),
Miguel Villalobos2
Estimated H-index: 2
(Rowan University)
+ 5 AuthorsPing Zhang2
Estimated H-index: 2
(Rowan University)
Objective Adipose-derived stem cells (ASCs) are a potential adult mesenchymal stem cell source for restoring endothelial function in patients with critical limb ischemia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) play a major role in angiogenesis and wound healing. This study evaluated the effects of FGF and VEGF on the proliferation, migration, and potential endothelial differentiation of human ASCs with regards to their use as endothelial cell substitutes. Methods ASCs were isolated from clinical lipoaspirates and cultured in M199 medium with fetal bovine serum (10%), FGF2 (10 ng/mL), VEGF (50 ng/mL), or combinations of FGF2 and VEGF. Cell proliferation rates, viability, and migration were measured by growth curves, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and scratch assays. For cell attachment determinations, ASCs were seeded onto a scaffold of small intestinal submucosa for 5 days. Endothelial differentiation capabilities of ASCs were confirmed by expression of endothelial cell-specific markers using quantitative polymerase chain reaction, immunofluorescence staining, and cord formation on Matrigel (BD Biosciences, San Jose, Calif). PD173074, a selective inhibitor of FGF receptor, was used to confirm the importance of FGF signaling. Results ASCs treated with FGF or combinations of FGF and VEGF showed increased proliferation rates and consistent differentiation toward an endothelial cell lineage increase in platelet endothelial cell adhesion molecule (CD31), von Willebrand factor, endothelial nitric oxide synthase, and vascular endothelial cadherin message, and in protein and cord formation on Matrigel. FGF and VEGF stimulated ASC migration and increased the attachment and retention after seeding onto a matrix graft of small intestinal submucosa. Blockade of FGF signaling with PD173074 abrogated ASC endothelial cell differentiation potential. Conclusions These results indicate that FGF and VEGF are ASC promoters for proliferation, migration, attachment, and endothelial differentiation. FGF and VEGF have a costimulatory effect on ASC endotheliogenesis. These results further suggest that ASCs with enhanced FGF signaling may potentially be used for tissue engineering and cell-based therapies in patients with critical limb ischemia.
📖 Papers frequently viewed together
131 Citations
809 Citations
16 Citations
#1Stephen McIlhenny (Thomas Jefferson University)H-Index: 10
#2Ping Zhang (Thomas Jefferson University)H-Index: 14
Last. Paul DiMuzio (Thomas Jefferson University)H-Index: 21
view all 11 authors...
This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expressi...
24 CitationsSource
#1Hossein BazmaraH-Index: 8
#2Madjid Soltani (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 22
Last. Arman Rahmim (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 34
view all 6 authors...
Sprouting angiogenesis and capillary network formation are tissue scale phenomena. There are also sub-scale phenomena involved in angiogenesis including at the cellular and intracellular (molecular) scales. In this work, a multiscale model of angiogenesis spanning intracellular, cellular, and tissue scales is developed in detail. The key events that are considered at the tissue scale are formation of closed flow path (that is called loop in this article) and blood flow initiation in the loop. At...
17 CitationsSource
#1Noriko Kitamura (Toho University)H-Index: 4
#2Terumitsu Hasebe (Tokai University)H-Index: 18
Last. Hitoshi Terada (Toho University)H-Index: 18
view all 7 authors...
Aim: The use of drug-eluting stents has reduced the incidence of in-stent restenosis following percutaneous coronary intervention; however, almost all drugs eluting from polymers on stents induce antiproliferative effects on vascular endothelial and vascular smooth muscle cells. Due to injury of the endothelium and delayed reendothelialization, the risk of thrombosis increases over time. Enhancing rapid reendothelialization after stent placement is important for solving these problems. Basic fib...
8 CitationsSource
#1Hiroshi Mizuno (Juntendo University)H-Index: 35
#2Morikuni TobitaH-Index: 17
Last. A. Cagri Uysal (Başkent University)H-Index: 4
view all 3 authors...
The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly benef...
468 CitationsSource
#1Ping Zhang (Thomas Jefferson University)H-Index: 14
#2Neil MoudgillH-Index: 8
Last. Paul DiMuzioH-Index: 21
view all 8 authors...
Adipose-derived stem cells (ASCs) possess significant therapeutic potential for tissue engineering and regeneration. This study investigates the endothelial differentiation and functional capacity of ASCs isolated from elderly patients. Isolation of ASCs from 53 patients (50–89 years) revealed that advanced age or comorbidity did not negatively impact stem cell harvest; rather, higher numbers were observed in older donors (>70 years) than in younger. ASCs cultured in endothelial growth medium-2 ...
72 CitationsSource
#1Bettina Lindroos (UTA: University of Tampere)H-Index: 9
#2Riitta Suuronen (TUT: Tampere University of Technology)H-Index: 57
Last. Susanna Miettinen (UTA: University of Tampere)H-Index: 42
view all 3 authors...
Adipose stem cells (ASCs) are an attractive and abundant stem cell source with therapeutic applicability in diverse fields for the repair and regeneration of acute and chronically damaged tissues. Importantly, unlike the human bone marrow stromal/stem stem cells (BMSCs) that are present at low frequency in the bone marrow, ASCs can be retrieved in high number from either liposuction aspirates or subcutaneous adipose tissue fragments and can easily be expanded in vitro. ASCs display properties si...
305 CitationsSource
#1Bradley T. Estes (Duke University)H-Index: 20
#2Farshid Guilak (Duke University)H-Index: 119
Stem cells can easily be harvested from adipose tissue in large numbers for use in tissue engineering approaches for cartilage repair or regeneration. In this chapter, we describe in vitro tissue engineering models that we have used in our laboratory for the chondrogenic induction of adipose-derived stem cell (ASC). In addition to the proper growth factor environment, chondrogenesis requires cells to be maintained in a rounded morphology in three-dimensional (3D) culture, and thus properties of ...
40 CitationsSource
#1J. Peter Rubin (University of Pittsburgh)H-Index: 61
#2Kacey G. Marra (University of Pittsburgh)H-Index: 64
: Autologous fat transplantation has revolutionized soft tissue reconstruction, but conventional methods remain unpredictable as graft resorption rates are high due to lack of vascularization. The advent of adipose-derived stem cells (ASCs) has led to improvement of fat grafting outcomes, in part to their ability to undergo facile differentiation into adipose tissue, their angiogenic properties, and their ability to express and secrete multiple growth factors. This chapter discusses the isolatio...
24 CitationsSource
#1Bradley T. Estes (Duke University)H-Index: 20
#2Brian O. Diekman (Duke University)H-Index: 16
Last. Farshid Guilak (Duke University)H-Index: 119
view all 4 authors...
The ability to isolate, expand, and differentiate adult stem cells into a chondrogenic lineage is an important step in the development of tissue engineering approaches for cartilage repair or regeneration for the treatment of joint injury or osteoarthritis, or for application in plastic or reconstructive surgery. Adipose-derived stem cells (ASCs) provide an abundant and easily accessible source of adult stem cells for use in such regenerative approaches. This protocol describes the isolation of ...
414 CitationsSource
#1Candace A. Brayfield (University of Pittsburgh)H-Index: 8
#2Kacey G. MarraH-Index: 64
Last. J. Peter RubinH-Index: 61
view all 3 authors...
The repair of soft tissue defects, particularly after trauma and oncologic surgery, represents a major clinical challenge. While current reconstructive procedures can move soft tissue from other areas of the body, there remains an unmet need for new modalities that are less invasive and more precise. Adipose tissue is the key component necessary for soft tissue reconstruction. This review will discuss the discovery and potential of adult stem therapies in the regeneration of adipose tissue. Adip...
26 CitationsSource
Cited By28
#1Xin Shi (Southern Medical University)
#2Liyuan Jiang (CSU: Central South University)H-Index: 6
Last. Jun Liu (Xiangnan University)H-Index: 1
view all 15 authors...
The management of diabetic wounds is still a therapeutic challenge in clinics. Current tissue-engineering strategies for diabetic wound healing are insufficient owing to lacking an appropriate scaffold that can largely load stem cells and induce the interacted stem cells forming granulation tissue. Herein, we fabricated a book-shaped decellularized dermal matrix (BDDM). This BDDM shows a high resemblance to native dermal tissue in histology, microstructure and ingredients, is noncytotoxicity and...
#1Ameneh Jafari (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 3
#2Mostafa Rezaei-Tavirani (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 17
Last. Hassan Niknejad (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 26
view all 5 authors...
Cancer is a leading cause of death in both developed and developing countries, and because of population growth and aging, it is a growing medical burden worldwide. With robust development in medicine, the use of stem cells has opened new treatment modalities in cancer therapy. In adult stem cells, mesenchymal stem cells (MSCs) are showing rising promise in cancer treatment due to their unique properties. Among different sources of MSCs, human amniotic fluid/membrane is an attractive and suitabl...
1 CitationsSource
Vascular endothelial growth factor-A165 (VEGF-A165) and fibroblast growth factor-2 (FGF-2) are currently used for the functionalization of biomaterials designed for tissue engineering. We have developed a new simple method for heterologous expression and purification of VEGF-A165 and FGF-2 in the yeast expression system of Pichia pastoris. The biological activity of the growth factors was assessed in cultures of human and porcine adipose tissue-derived stem cells (ADSCs) and human umbilical vein...
#1Zhi-Jie Liang (Guangxi Medical University)H-Index: 5
#2Donglin Huang (Guangxi Medical University)
view all 9 authors...
Abstract Advanced platelet-rich fibrin (A-PRF) is an autogenous biological material obtained from peripheral blood. A-PRF extract (A-PRFe) contains a high concentration of various cytokines that are increasingly appreciated for their roles in improving stem cell repairing function during tissue regeneration. However, the optimal A-PRFe concentration to stimulate stem cells is unknown. This study aimed to identify the optimal concentrations of A-PRFe to promote adipogenic and osteogenic different...
Tissue engineering is a rapidly developing field with many potential clinical applications in tissue and organ regeneration. The development of a mature and stable vasculature within these engineered tissues (ET) remains a significant obstacle. Currently, several growth factors (GFs) have been identified to play key roles within in vivo angiogenesis, including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), FGF and angiopoietins. In this article we attempt to bu...
1 CitationsSource
#1Baicheng Yi (HKU: University of Hong Kong)H-Index: 1
#2Waruna Lakmal Dissanayaka (HKU: University of Hong Kong)H-Index: 14
Last. Chengfei Zhang (HKU: University of Hong Kong)H-Index: 31
view all 3 authors...
Abstract Introduction Incorporating fully assembled microvascular networks into bioengineered dental pulp constructs can significantly enhance functional blood flow and tissue survival upon transplantation. Endothelial cells (ECs), cellular building blocks of vascular tissue, play an essential role in the process of prevascularization. However, obtaining sufficient ECs from a suitable source for translational application is challenging. Dental stem cells (DSCs), which exhibit a robust proliferat...
#1Roman MatějkaH-Index: 3
Last. Jan PirkH-Index: 18
view all 15 authors...
1 CitationsSource
#1Junsheng LiH-Index: 2
#2Qian ZhangH-Index: 1
Last. Jizong ZhaoH-Index: 1
view all 6 authors...
Stroke, a global disease with a high disability rate, has limited options for functional rehabilitation and results in an adverse impact on patients’ lives. In recent years, mesenchymal stem cells (MSCs) have become a new focus of treatment owing to their potential for neuroregeneration. MSCs have demonstrated therapeutic efficacy capable of cell migration, angiogenesis, immunomodulation, neuroprotection and neural circuit reconstruction. The paracrine action of MSCs can also exert neurotrophic ...
8 CitationsSource
#1M. di Somma (University of Brescia)H-Index: 1
#2Maria Vliora (University of Brescia)H-Index: 2
Last. Stefania Mitola (University of Brescia)H-Index: 32
view all 11 authors...
Obesity and metabolic disorders are important public health problems. In this review, the role of vasculature network and VEGF in the adipose tissue maintenance and supplementation is discussed. Angiogenesis is a key process implicated in regulation of tissues homeostasis. Dysregulation of new blood vessels formation may be crucial and contribute to the onset of several pathological conditions, including metabolic syndrome-associated disorders. Adipose tissue homeostasis is fine regulated by vas...
9 CitationsSource
#1Jong Ho Kim (KU: Korea University)H-Index: 13
#1Jong-Ho Kim (KU: Korea University)H-Index: 3
Last. Do Sun Lim (KU: Korea University)H-Index: 29
view all 8 authors...
Thymosin β4 (Tβ4) is a G-actin sequestering protein that contributes to diverse cellular activities, such as migration and angiogenesis. In this study, the beneficial effects of combined cell therapy with Tβ4 and human adipose-derived stem cells (hASCs) in a mouse ischemic hindlimb model were investigated. We observed that exogenous treatment with Tβ4 enhanced endogenous TMSB4X mRNA expression and promoted morphological changes (increased cell length) in hASCs. Interestingly, Tβ4 induced the act...