Mesenchymal Stem Cell Injection Induces Cardiac Nerve Sprouting and Increased Tenascin Expression in a Swine Model of Myocardial Infarction

Pak, Hui-Nam; Qayyum, Mohammed; Kim, Dave T.; Hamabe, Akira; Miyauchi, Yasushi; Lill, Michael; Frantzen, Malkar; Takizawa, Kazuyasu; Chen, Lan S.; Fishbein, Michael C.; Sharifi, Behrooz G.; Chen, Peng‐Sheng; Makkar, Raj

doi:10.1046/j.1540-8167.2003.03124.x

Cited by 115 publications

(100 citation statements)

References 31 publications

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“…Thus, the expression of SCX and TNC is considered as the marker of tenogenic differentiation in vitro (Schweitzer et al 2001;Hsia 2005; Chiquet-Ehrismann and Tucker 2004). Though, it was illuminated later that in some fibroblasts these two genes were slightly expressed, the expression level in tenocytes was much higher (Pak et al 2003;Seo et al 2004). On the other hand, Collagen types I, III, V, IX, X, XI, XII and XIV are known or thought to be involved in bone, tendon or ligament healing, especially Col I and Col III are the main collagens found in connective tissues, such as tendon and ligament.…”

Section: Discussionmentioning

confidence: 99%

Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells

Luo

Song

et al. 2009

Cytotechnology

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Recent evidences have suggested that humoral factors released from the appropriate cocultured cells influenced the expansion and differentiation of mesenchymal stem cells (MSCs). However, little is known about the proliferation and differentiation of MSCs subjected to co-culture condition with tenocytes. In this study, we aimed to establish a coculture system of MSCs and tenocytes and investigate the proliferation and tendon/ligament related gene expression of MSCs. MTT assay was used to detect the expansion of MSCs. Semi-quantitative RT-PCR was performed to investigate the expression of proliferation associated c-fos gene and tendon/ligament related genes, including type I collagen (Col I), type III collagen (Col III), tenascin C and scleraxis. Significant increase in MSCs expansion was observed after 3 days of co-culture with tenocytes. The c-fos gene expression was found distinctly higher than for control group on day 4 and day 7 of co-culture. The mRNA expression of four tendon/ligament related genes was significantly up-regulated after 14 days of co-culture with tenocytes. Thus, our research indicates that indirect coculture with tenocytes promotes the proliferation and mRNA expression of tendon/ligament related genes in MSCs, which suggests a directed differentiation of MSCs into tendon/ligament.

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Section: Discussionmentioning

confidence: 99%

Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells

Luo

Song

et al. 2009

Cytotechnology

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“…Furthermore, significantly higher episodes of ventricular fibrillation, both spontaneous and induced, occurred in the hypercholesterolemic rabbits, indicating a lower vulnerability to fibrillation. 49 Cardiac nerve sprouting appears to be highly plastic and has been has been shown in other models of heart failure including rapid pacing where dogs with the most hyperinnervation have the highest risk of sudden cardiac death, 50 in stem cell transplantation, 51 and radiofrequency ablation. 52 Heart failure is also known to cause spatially heterogenous remodeling of cardiomyocytes, with further remodeling of cardiac ion channels, including Ca, K, Cl, and Ca transporters and enzymes in the border zones surrounding the infarct.…”

Section: Myocardial Infarction Heart Failure and Sympathetic Innervmentioning

confidence: 97%

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

336

233

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The cardiac autonomic nervous system consists of 2 branches-the sympathetic and the parasympathetic systems-that work in a delicately tuned, yet opposing fashion in the heart. This extrinsic control mechanism can dominate intrinsic regulatory mechanisms that modulate heart rate and cardiac output. These branches differ in their neurotransmitters (norepinephrine and acetylcholine) and exert stimulatory or inhibitory effects on target tissue via adrenergic and muscarinic receptors. Stimulation of the sympathetic branch exerts facilitatory effects on function, increasing heart rate and myocardial contractility, whereas the stimulation of the parasympathetic branch exerts inhibitory effects that decrease heart rate and contractility. The interplay between these two branches is complex and susceptible to control at several levels, from centrally mediated baroreceptors and chemoreceptors to local interneuronal interactions.Alterations in autonomic function occur in several interrelated cardiac conditions including sudden cardiac death, congestive heart failure, diabetic neuropathy, and myocardial ischemia. Although the full extent of these changes has not been elucidated, multiple autonomic remodeling mechanisms have been observed at both the neuronal fiber and myocardial cellular level that contribute to an arrhythmogenic substrate. We describe the anatomy of both systems in this review. However, the review will premdominantly focus on the sympathetic system, whose role in the modulation of cardiac arrhythmias is slightly better delineated. Cardiac Autonomic Innervation: NeuroanatomyBoth branches of the autonomic nervous system are composed of both afferent and efferent as well interneuronal fibers (Fig 1). Sympathetic innervation originates mainly in the right and left stellate ganglia. These fibers travel along the epicardial vascular structures of the heart and penetrate into the underlying myocardium similar to coronary vessels and end as sympathetic nerve terminals reaching the endocardium. Based on norepinephrine content studies, a gradient exists in sympathetic innervation from atria to the ventricles and from base to apex of the heart. Therefore, the atria are most densely innervated, but the ventricles are also supplied with a sympathetic network, most densely at the base. 1 Parasympathetic effects are carried by the right and left vagus nerves, originating in the medulla. The vagus nerve further divides into the superior and inferior cardiac nerves, finally merging with the postganglionic sympathetic neurons to form a plexus of nerves at the base of the heart, known as the cardiac plexus. In contrast to sympathetic neurons, after parasympathetic fibers cross the atrioventricular (AV) groove along the surface of the heart,

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“…Numerous studies with a variety of animal models have shown that MSCs may be useful in the process of repairation or regeneration of damaged bones, cartilages, or myocardial tissues, thus representing a new source to treat congenital or degenerative disorders (Muguruma et al 2003;Pak et al 2003;Parsons et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Human adipose tissue derived mesenchymal stem cells are resistant to several chemotherapeutic agents

Liang

Xia

et al. 2011

Cytotechnology

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Human adipose derived mesenchymal stem cells (ADMSCs) are multipotential stem cells, originated from the vascular stromal compartment of fat tissues which can be used as an alternative cell source for many different cell therapies. However, their response to chemotherapeutic agants remains unknown. Here we assessed the acute direct effects of individual chemotherapeutic drug on ADMSCs. Using an in vitro culture system, the response of ADMSCs to the three chemotherapeutic agents cisplatin, comptothecin and vincristine was determined in comparison with that of testicular germ cell tumour (TGCT) cell line. The recovery of cell numbers following exposure to chemotherapeutic agents were also evaluated. Our results showed that human ADMSCs were resistant to chemo-therapeutic agents which are commonly used in clinic, the full recovery was seen respectively in ADMSCs after the drug treatment. Moreover, ADMSCs maintained their stem cell characteristics in vitro after the exposure to all chemotherapeutic agents.

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Mesenchymal Stem Cell Injection Induces Cardiac Nerve Sprouting and Increased Tenascin Expression in a Swine Model of Myocardial Infarction

Abstract: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac nerve sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection.

Cited by 115 publications

References 31 publications

Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells

Indirect co-culture with tenocytes promotes proliferation and mRNA expression of tendon/ligament related genes in rat bone marrow mesenchymal stem cells

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Human adipose tissue derived mesenchymal stem cells are resistant to several chemotherapeutic agents

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