Generation of a Purified iPSC-Derived Smooth Muscle-like Population for Cell Sheet Engineering

Kwong, George; Márquez, Héctor; Yang, Chian; Wong, Joyce Y.; Kotton, Darrell N.

doi:10.1016/j.stemcr.2019.07.014

Cited by 20 publications

(26 citation statements)

References 54 publications

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“…Like RT-PCR results, induced DPSCs (under both culturing conditions) displayed positive immunostaining results for α -SMA, SM22- α , and CALP ( Figure 5 ), inconsistently expressed SMTN, but could not show positive staining results for main matured marker MHY-11 (data not shown). These results indicate that differentiated SMLCs were not properly matured and were having synthetic phenotype as shown by previously published reports [ 27 ]. Furthermore, differentiated cells from both the treatment groups were assessed for their ability to contract collagen gel lattices in a time-dependent manner.…”

Section: Discussionsupporting

confidence: 80%

Human Dental Pulp-Derived Mesenchymal Stem Cell Potential to Differentiate into Smooth Muscle-Like Cells In Vitro

Bharti

Kang

et al. 2021

BioMed Research International

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Previous studies have shown that mesenchymal stem cells (MSCs) derived from various tissue sources can be differentiated into smooth muscle-like cells (SMLCs) in vitro. In this paper, dental pulp-derived mesenchymal stem cells (DPSCs) were evaluated for their differentiation ability towards smooth muscle-like cells (SMLCs) under the effect of widely used cytokines (TGF-β1 and PDGF-BB) with special focus on different culturing environments. For this purpose, both the commercially used culturing plates (Norm-c) and 0.1% gelatin-precoated (Gel-c) plates were used. Isolated cells displayed plastic adherence, pluripotency and cell surface marker profiling, and adipogenic and osteogenic differentiation potential with lineage specific marker expression. Differentiated cells induced under different culturing plates showed successful differentiation into SMLCs by positively expressing smooth muscle cell (SMC) specific markers both at the mRNA and protein levels. Gelatin coating could substantially enhance DPSC differentiation potential than Norm-c-induced cells. However, the absence of mature marker MHY-11 by immunostaining results from all treatment groups further indicated the development of immature and synthetic SMLCs. Finally, it was concluded that DPSC differentiation ability into SMLCs can be enhanced under cytokine treatment as well as by altering the cellular niche by precoating the culturing plates with suitable substrates. However, to get fully functional, contractile, and mature SMLCs, still many different cytokine cocktail combinations and more suitable coating substrates will be needed.

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Section: Discussionsupporting

confidence: 80%

Human Dental Pulp-Derived Mesenchymal Stem Cell Potential to Differentiate into Smooth Muscle-Like Cells In Vitro

Bharti

Kang

et al. 2021

BioMed Research International

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“…However, the specificity of PSCs exosomes in entering and eliciting reparative functions in each of the different types of cells in the diseased heart is still unknown. It is factual that both embryonic and induced PSCs differentiate into various kinds of heart cells, such as CMs, endothelial cells [ 67 ], smooth muscle cells [ 68 ], and epicardial cells, which further differentiate into cardiac stromal cells and cardiac fibroblasts in vitro [ 69 ]. In the in vitro stages of PSC-directed differentiation, there is a precursor or progenitor stage for every cell type during the differentiation process.…”

Section: Stem Cell Exosomes For Cardiac Repairmentioning

confidence: 99%

Unfathomed Nanomessages to the Heart: Translational Implications of Stem Cell-Derived, Progenitor Cell Exosomes in Cardiac Repair and Regeneration

Thej

Kishore

2021

Cells

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Exosomes formed from the endosomal membranes at the lipid microdomains of multivesicular bodies (MVBs) have become crucial structures responsible for cell communication. This paracrine communication system between a myriad of cell types is essential for maintaining homeostasis and influencing various biological functions in immune, vasculogenic, and regenerative cell types in multiple organs in the body, including, but not limited to, cardiac cells and tissues. Characteristically, exosomes are identifiable by common proteins that participate in their biogenesis; however, many different proteins, mRNA, miRNAs, and lipids, have been identified that mediate intercellular communication and elicit multiple functions in other target cells. Although our understanding of exosomes is still limited, the last decade has seen a steep surge in translational studies involving the treatment of cardiovascular diseases with cell-free exosome fractions from cardiomyocytes (CMs), cardiosphere-derived cells (CDCs), endothelial cells (ECs), mesenchymal stromal cells (MSCs), or their combinations. However, most primary cells are difficult to culture in vitro and to generate sufficient exosomes to treat cardiac ischemia or promote cardiac regeneration effectively. Pluripotent stem cells (PSCs) offer the possibility of an unlimited supply of either committed or terminally differentiated cells and their exosomes for treating cardiovascular diseases (CVDs). This review discusses the promising prospects of treating CVDs using exosomes from cardiac progenitor cells (CPCs), endothelial progenitor cells (EPCs), MSCs, and cardiac fibroblasts derived from PSCs.

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“…Improving the Quality of the Cells A universal concern regarding iPSC-derived cells is that they tend to be very heterogeneous, and this is no exception for iPSCderived vascular cells (Karakikes et al, 2015;Paik et al, 2018;Kwong et al, 2019;Volpato and Webber, 2020). Drug testing using heterogeneous cell populations may lead to an inaccurate conclusion, especially if it is based on ensemble measurements (Altschuler and Wu, 2010).…”

Section: Moving Forward-what Is Next?mentioning

confidence: 99%

Human Induced Pluripotent Stem Cells as a Screening Platform for Drug-Induced Vascular Toxicity

Cunningham

Zhang

et al. 2021

Front. Pharmacol.

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Evaluation of potential vascular injury is an essential part of the safety study during pharmaceutical development. Vascular liability issues are important causes of drug termination during preclinical investigations. Currently, preclinical assessment of vascular toxicity primarily relies on the use of animal models. However, accumulating evidence indicates a significant discrepancy between animal toxicity and human toxicity, casting doubt on the clinical relevance of animal models for such safety studies. While the causes of this discrepancy are expected to be multifactorial, species differences are likely a key factor. Consequently, a human-based model is a desirable solution to this problem, which has been made possible by the advent of human induced pluripotent stem cells (iPSCs). In particular, recent advances in the field now allow the efficient generation of a variety of vascular cells (e.g., endothelial cells, smooth muscle cells, and pericytes) from iPSCs. Using these cells, different vascular models have been established, ranging from simple 2D cultures to highly sophisticated vascular organoids and microfluidic devices. Toxicity testing using these models can recapitulate key aspects of vascular pathology on molecular (e.g., secretion of proinflammatory cytokines), cellular (e.g., cell apoptosis), and in some cases, tissue (e.g., endothelium barrier dysfunction) levels. These encouraging data provide the rationale for continuing efforts in the exploration, optimization, and validation of the iPSC technology in vascular toxicology.

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Generation of a Purified iPSC-Derived Smooth Muscle-like Population for Cell Sheet Engineering

Cited by 20 publications

References 54 publications

Human Dental Pulp-Derived Mesenchymal Stem Cell Potential to Differentiate into Smooth Muscle-Like Cells In Vitro

Human Dental Pulp-Derived Mesenchymal Stem Cell Potential to Differentiate into Smooth Muscle-Like Cells In Vitro

Unfathomed Nanomessages to the Heart: Translational Implications of Stem Cell-Derived, Progenitor Cell Exosomes in Cardiac Repair and Regeneration

Human Induced Pluripotent Stem Cells as a Screening Platform for Drug-Induced Vascular Toxicity

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