Cadherin‐5 facilitated the differentiation of human induced pluripotent stem cells into sinoatrial node‐like pacemaker cells by regulating β‐catenin

Zhang, Wei; Wang, Fengyuan; Yin, Lin; Tang, Yanhong; Wang, Xi; Huang, Congxin

doi:10.1002/jcp.31161

Cited by 3 publications

(9 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the limited treatment options available, different strategies have been used to develop biological pacemakers that could potentially replace the electronic devices currently used for the treatment of SND and other arrhythmias. For reviews and the most recent progress, please refer to references [288][289][290][291][292] . In line with the focus of this review, it is worth mentioning that many of the approaches used to generate a biological pacemaker involve HCN channels.…”

Section: Hcn Channels In Disease and Therapymentioning

confidence: 99%

Pacemaker Channels and the Chronotropic Response in Health and Disease

Hennis,

Piantoni,

Biel

et al. 2024

Circulation Research

View full text Add to dashboard Cite

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease—including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating β-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate–sensitive hyperpolarization–activated current (I f ) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate–dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond.

show abstract

Section: Hcn Channels In Disease and Therapymentioning

confidence: 99%

Pacemaker Channels and the Chronotropic Response in Health and Disease

Hennis,

Piantoni,

Biel

et al. 2024

Circulation Research

View full text Add to dashboard Cite

show abstract

“…More recent findings bring the role of cadherin-5 protein (CDH5 or VE-Cadherin) on the differentiation of hiPSC-PMs [ 79 ]. CHD5 is a cell adhesion glycoprotein expressed in vascular endothelial cells [ 80 ].…”

Section: Protocols To Differentiate Hipsc-pmsmentioning

confidence: 99%

“…CHD5 is a cell adhesion glycoprotein expressed in vascular endothelial cells [ 80 ]. Treatment with CDH5 during cardiac differentiation led to an increased proportion of hiPSC-PMs [ 79 ] ( Figure 4 ). In particular, CDH5 seems to synergically support Wnt/β-catenin signaling to enhance TCF activity [ 81 ] when added between days 5 and 7.…”

Section: Protocols To Differentiate Hipsc-pmsmentioning

confidence: 99%

“… Summary of experimental designs to induce hiPSC-PMs through transgene-free methods [ 69 , 75 , 76 , 77 , 78 , 79 ]. …”

Section: Protocols To Differentiate Hipsc-pmsmentioning

confidence: 99%

“…In general, hiPSC-PMs have faster AP rate and slower maximum upstroke velocity (dV/dt max ) [ 65 , 67 , 68 , 69 , 75 , 76 , 77 , 79 ] compared to atrial- and ventricular-like hiPSC-CMs. As mentioned above, HCN1 and HCN4 contribute to the generation of I f in the human SAN.…”

Section: Electrophysiological Properties Of Hipsc-pmsmentioning

confidence: 99%

See 2 more Smart Citations

State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells

Torre,

Mangoni,

Lacampagne

et al. 2024

IJMS

View full text Add to dashboard Cite

Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes raise the possibility of generating pluripotent stem cells from a wide range of human diseases. In the cardiology field, hiPSCs have been used to address the mechanistic bases of primary arrhythmias and in investigations of drug safety. These studies have been focused primarily on atrial and ventricular pathologies. Consequently, many hiPSC-based cardiac differentiation protocols have been developed to differentiate between atrial- or ventricular-like cardiomyocytes. Few protocols have successfully proposed ways to obtain hiPSC-derived cardiac pacemaker cells, despite the very limited availability of human tissues from the sinoatrial node. Providing an in vitro source of pacemaker-like cells would be of paramount importance in terms of furthering our understanding of the mechanisms underlying sinoatrial node pathophysiology and testing innovative clinical strategies against sinoatrial node dysfunction (i.e., biological pacemakers and genetic- and pharmacological- based therapy). Here, we summarize and detail the currently available protocols used to obtain patient-derived pacemaker-like cells.

show abstract

Stem Cell Therapy against Ischemic Heart Disease

Tsai,

Sun

2024

IJMS

View full text Add to dashboard Cite

Ischemic heart disease, which is one of the top killers worldwide, encompasses a series of heart problems stemming from a compromised coronary blood supply to the myocardium. The severity of the disease ranges from an unstable manifestation of ischemic symptoms, such as unstable angina, to myocardial death, that is, the immediate life-threatening condition of myocardial infarction. Even though patients may survive myocardial infarction, the resulting ischemia-reperfusion injury triggers a cascade of inflammatory reactions and oxidative stress that poses a significant threat to myocardial function following successful revascularization. Moreover, despite evidence suggesting the presence of cardiac stem cells, the fact that cardiomyocytes are terminally differentiated and cannot significantly regenerate after injury accounts for the subsequent progression to ischemic cardiomyopathy and ischemic heart failure, despite the current advancements in cardiac medicine. In the last two decades, researchers have realized the possibility of utilizing stem cell plasticity for therapeutic purposes. Indeed, stem cells of different origin, such as bone-marrow- and adipose-derived mesenchymal stem cells, circulation-derived progenitor cells, and induced pluripotent stem cells, have all been shown to play therapeutic roles in ischemic heart disease. In addition, the discovery of stem-cell-associated paracrine effects has triggered intense investigations into the actions of exosomes. Notwithstanding the seemingly promising outcomes from both experimental and clinical studies regarding the therapeutic use of stem cells against ischemic heart disease, positive results from fraud or false data interpretation need to be taken into consideration. The current review is aimed at overviewing the therapeutic application of stem cells in different categories of ischemic heart disease, including relevant experimental and clinical outcomes, as well as the proposed mechanisms underpinning such observations.

show abstract

Cadherin‐5 facilitated the differentiation of human induced pluripotent stem cells into sinoatrial node‐like pacemaker cells by regulating β‐catenin

Cited by 3 publications

References 49 publications

Pacemaker Channels and the Chronotropic Response in Health and Disease

Pacemaker Channels and the Chronotropic Response in Health and Disease

State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells

Stem Cell Therapy against Ischemic Heart Disease

Contact Info

Product

Resources

About