scholarly journals Extracellular matrix protein laminin enhances mesenchymal stem cell (MSC) paracrine function through αvβ3/CD61 integrin to reduce cardiomyocyte apoptosis

2017 ◽  
Vol 21 (8) ◽  
pp. 1572-1583 ◽  
Author(s):  
Kai-Yen Peng ◽  
Yuan-Hung Liu ◽  
Yu-Wei Li ◽  
Betty Linju Yen ◽  
Men-Luh Yen
2018 ◽  
Vol 24 (11-12) ◽  
pp. 968-978 ◽  
Author(s):  
Aixin Cheng ◽  
Stuart A. Cain ◽  
Pinyuan Tian ◽  
Andrew K. Baldwin ◽  
Paweena Uppanan ◽  
...  

2018 ◽  
Vol 19 (3) ◽  
pp. 721-730 ◽  
Author(s):  
Hadi Hezaveh ◽  
Steffen Cosson ◽  
Ellen A. Otte ◽  
Guannan Su ◽  
Benjamin D. Fairbanks ◽  
...  

2019 ◽  
Vol 116 (6) ◽  
pp. 2042-2051 ◽  
Author(s):  
Giselle C. Yeo ◽  
Anthony S. Weiss

We challenge the conventional designation of structural matrix proteins primarily as supporting scaffolds for resident cells. The extracellular matrix protein tropoelastin is classically regarded as a structural component that confers mechanical strength and resilience to tissues subject to repetitive elastic deformation. Here we describe how tropoelastin inherently induces a range of biological responses, even in cells not typically associated with elastic tissues and in a manner unexpected of typical substrate-dependent matrix proteins. We show that tropoelastin alone drives mesenchymal stem cell (MSC) proliferation and phenotypic maintenance, akin to the synergistic effects of potent growth factors such as insulin-like growth factor 1 and basic fibroblast growth factor. In addition, tropoelastin functionally surpasses these growth factors, as well as fibronectin, in allowing substantial media serum reduction without loss of proliferative potential. We further demonstrate that tropoelastin elicits strong mitogenic and cell-attractive responses, both as an immobilized substrate and as a soluble additive, via direct interactions with cell surface integrins αvβ3 and αvβ5. This duality of action converges the long-held mechanistic dichotomy between adhesive matrix proteins and soluble growth factors and uncovers the powerful, untapped potential of tropoelastin for clinical MSC expansion and therapeutic MSC recruitment. We propose that the potent, growth factor-like mitogenic and motogenic abilities of tropoelastin are biologically rooted in the need for rapid stem cell homing and proliferation during early development and/or wound repair.


Small ◽  
2010 ◽  
Vol 6 (22) ◽  
pp. 2508-2508
Author(s):  
Aniruddh Solanki ◽  
Shreyas Shah ◽  
Kevin A. Memoli ◽  
Sung Young Park ◽  
Seunghun Hong ◽  
...  

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. SCI-2-SCI-2
Author(s):  
Marieke A. G. Essers

Infection is a common, natural form of stress, with which the body is regularly challenged. During infection or inflammation, cells of the immune system are responsible for fighting the invading pathogens. This leads to consumption of blood and immune cells due to mobilization of these cells to the site of infection, or by apoptosis as part of the host response to invading pathogens. Restoration of the balance of the hematopoietic system following successful elimination of the infection is a crucial part of the recovery of the body. In addition, both clinical and experimental data indicate that depending on the scale and duration, infection and inflammation can induce hematopoietic dysfunction compromising immune defense mechanisms and possibly contributing to the development of hematologic malignancies. Restoring the balance of the hematopoietic system depends on the replacement of lost immune cells by the activity of hematopoietic stem cells (HSCs). During the last ten years we and others could show that this so-called emergency hematopoiesis is driven by pro-inflammatory cytokines, who are increasingly produced upon infection or inflammation in the bone marrow and can directly drive the activation of normally quiescent HSCs. An interesting observation from these data is the often opposing impact of these pro-inflammatory cytokines on HSCs in vivo versus in vitro. Whereas in vivo treatment of mice with for example IFNα leads to a strong increase in proliferation of the HSCs, in vitro treatment with IFNα inhibits the HSCs. Furthermore, data from viral infection experiments have shown sustained alterations in the inflammatory cytokine/chemokine profile in the bone marrow weeks after the infection. All these data suggest that interactions of HSCs with their direct environment or signals from this environment are important for a proper response of the HSCs during environmental stress. Research in recent years has focused on unraveling the different components of the HSC stem cell niche. However, the molecular and cellular basis of the BM HSC niche, and signals exchanged between HSC and niche cells under stress conditions remain poorly understood. We initially focused on how the niche responds to inflammatory stress, and could show that the BM stem cell vascular niche was remodeled in response to IFNα. IFNα treatment of mice resulted in increased BM vascularity, expression of key inflammatory and endothelial-stimulatory markers on ECs and increased BM vascular leakiness. These data indicate a novel acute response of the BM vasculature to primary inflammatory signaling, suggesting alterations of the HSC niche in response to stress. ECs are not the only cells in the BM niche responding to inflammatory stress. Using different mouse models and single cell sequencing technology we are currently not only investigating the impact of inflammatory stress on the other components of the niche but also try to unravel the possible changes in interactions and signals between the HSCs and the niche. One example is our data on the role of the extracellular matrix protein Matrilin-4 (Matn4) in the regulation of the HSC response. Under homeostasis high expression of Matn-4 in HSCs confers a resistance to stress stimuli. In situations of acute stress, such as an infection or transplantation, this protection is rapidly lost through down-regulation of Matn-4, allowing HSCs to efficiently replenish the blood system. Thus, these data indicate an important role for the control of the interactions of HSCs with the extracellular matrix in regulating the HSC stress response in vivo. In summary, investigating the response of the bone marrow niche and the role of stem cell-ECM-niche interactions in controlling the HSC stress response will help us to better understand the shortterm and longterm impact of infection and inflammation on the HSCs and their niche. Potential Articles of Interest: Hirche C, Frenz T, Haas S, et al (2017). Systemic Virus Infections differentially modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo. Cell Reports19: 2345-56Velten L, Haas SF, Raffel S, et al (2017). Human haematopoietic stem cell lineage commitment is a continuous process. Cell Biol.19: 271-281Prendergast AM, Kuck A, van Essen M, et al (2017). IFNa mediated remodeling of endothelial cells in the bone marrow niche. Haematologica,102: 445-453Uckelmann H, Blaszkiewicz S, Nicolae C, et al (2016). Extracellular matrix protein Matrilin-4 regulates stress-induced HSC proliferation via CXCR4. J Exp. Med.213: 1961-1971Haas S, Hansson J, Klimmeck D, et al (2015). Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors. Cell Stem Cell17: 422-34 Disclosures No relevant conflicts of interest to declare.


2007 ◽  
Vol 177 (4S) ◽  
pp. 421-422
Author(s):  
Ganka Nikolova ◽  
Christian O. Twiss ◽  
Hane Lee ◽  
Nelson Stanley ◽  
Janet Sinsheimer ◽  
...  

Author(s):  
Aniel Moya-Torres ◽  
Monika Gupta ◽  
Fabian Heide ◽  
Natalie Krahn ◽  
Scott Legare ◽  
...  

Abstract The production of recombinant proteins for functional and biophysical studies, especially in the field of structural determination, still represents a challenge as high quality and quantities are needed to adequately perform experiments. This is in part solved by optimizing protein constructs and expression conditions to maximize the yields in regular flask expression systems. Still, work flow and effort can be substantial with no guarantee to obtain improvements. This study presents a combination of workflows that can be used to dramatically increase protein production and improve processing results, specifically for the extracellular matrix protein Netrin-1. This proteoglycan is an axon guidance cue which interacts with various receptors to initiate downstream signaling cascades affecting cell differentiation, proliferation, metabolism, and survival. We were able to produce large glycoprotein quantities in mammalian cells, which were engineered for protein overexpression and secretion into the media using the controlled environment provided by a hollow fiber bioreactor. Close monitoring of the internal bioreactor conditions allowed for stable production over an extended period of time. In addition to this, Netrin-1 concentrations were monitored in expression media through biolayer interferometry which allowed us to increase Netrin-1 media concentrations tenfold over our current flask systems while preserving excellent protein quality and in solution behavior. Our particular combination of genetic engineering, cell culture system, protein purification, and biophysical characterization permitted us to establish an efficient and continuous production of high-quality protein suitable for structural biology studies that can be translated to various biological systems. Key points • Hollow fiber bioreactor produces substantial yields of homogenous Netrin-1 • Biolayer interferometry allows target protein quantitation in expression media • High production yields in the bioreactor do not impair Netrin-1 proteoglycan quality Graphical abstract


2002 ◽  
Vol 267 (4) ◽  
pp. 440-446 ◽  
Author(s):  
A. Kapetanopoulos ◽  
F. Fresser ◽  
G. Millonig ◽  
Y. Shaul ◽  
G. Baier ◽  
...  

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