Use of Self-Assembling Peptides to Enhance Stem Cell Function for Therapeutic Angiogenesis

The use of nanomaterials for biomedical applications has become a promising field in regenerative medicine. Self-assembling peptides (SAPs) have been proposed as a good candidate because they are able to self-assemble into stable hydrogels and interact with cells or molecules when combined together. This in turn can lead to the improved survival or action of cells or molecules to obtain the desired effects. In this study, we investigated whether the combination of mesenchymal stem cells (MSCs) with SAPs could improve angiogenesis in ischemic hindlimbs of rats compared to MSC or SAP treatment alone. The combination of MSCs and SAPs showed an overall higher expression of angiogenesis markers on fluorescent immunohistochemical analysis and a lower degree of fibrosis and cell apoptosis, which in turn led to an overall tendency for improved perfusion of the ischemic hindlimbs. Finally, SAPs also showed the ability to recruit endogenous host MSCs into the site of action, especially when modified to incorporate substance P as a functional motif, which when injected with exogenous MSCs, allowed for the dual presence of MSCs at the site of action. Overall, these results suggest that SAPs can be applied with stem cells to potentiate angiogenesis, with potential therapeutic application in vascular diseases.

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Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications

Stem Cells International ◽

10.1155/2016/1314709 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 89

Author(s):

Hongyan Tao ◽

Zhibo Han ◽

Zhong Chao Han ◽

Zongjin Li

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cardiovascular Diseases ◽

Vascular Diseases ◽

Intrinsic Property ◽

Cell Types ◽

Therapeutic Angiogenesis ◽

Endothelial Differentiation ◽

Clinical Parameters ◽

Multipotent Progenitors

Mesenchymal stem cells (MSCs) have shown their therapeutic potency for treatment of cardiovascular diseases owing to their low immunogenicity, ease of isolation and expansion, and multipotency. As multipotent progenitors, MSCs have revealed their ability to differentiate into various cell types and could promote endogenous angiogenesis via microenvironmental modulation. Studies on cardiovascular diseases have demonstrated that transplanted MSCs could engraft at the injured sites and differentiate into cardiomyocytes and endothelial cells as well. Accordingly, several clinical trials using MSCs have been performed and revealed that MSCs may improve relevant clinical parameters in patients with vascular diseases. To fully comprehend the characteristics of MSCs, understanding their intrinsic property and associated modulations in tuning their behaviors as well as functions is indispensable for future clinical translation of MSC therapy. This review will focus on recent progresses on endothelial differentiation and potential clinical application of MSCs, with emphasis on therapeutic angiogenesis for treatment of cardiovascular diseases.

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Application of induced pluripotent stem cells to model smooth muscle cell function in vascular diseases

Current Opinion in Biomedical Engineering ◽

10.1016/j.cobme.2017.02.005 ◽

2017 ◽

Vol 1 ◽

pp. 38-44 ◽

Cited By ~ 7

Author(s):

HaYeun Ji ◽

Hye Sung Kim ◽

Hae-Won Kim ◽

Kam W. Leong

Keyword(s):

Stem Cells ◽

Smooth Muscle ◽

Smooth Muscle Cell ◽

Induced Pluripotent Stem Cells ◽

Muscle Cell ◽

Pluripotent Stem Cells ◽

Cell Function ◽

Vascular Diseases ◽

Induced Pluripotent

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Faculty Opinions recommendation of Regional anatomic and age effects on cell function of human adipose-derived stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108281.564306 ◽

2008 ◽

Author(s):

Dietmar Werner Hutmacher

Keyword(s):

Stem Cells ◽

Cell Function ◽

Age Effects ◽

Adipose Derived Stem Cells

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Stem Cell Function, Self-Renewal, Heterogeneity, and Regenerative Potential in Skeletal Muscle Stem Cells

Recent Patents on Regenerative Medicine ◽

10.2174/2210296511202010011 ◽

2012 ◽

Vol 2 (1) ◽

pp. 11-21

Author(s):

Silvia Cristini ◽

Giulio Alessandri ◽

Francesco Acerbi ◽

Daniela Tavian ◽

Eugenio A. Parati ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Stem Cell ◽

Cell Function ◽

Self Renewal ◽

Muscle Stem Cells ◽

Skeletal Muscle Stem Cells

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Stem Cell Function, Self-Renewal, Heterogeneity, and Regenerative Potential in Skeletal Muscle Stem Cells

Recent Patents on Regenerative Medicine ◽

10.2174/2210297311202010011 ◽

2012 ◽

Vol 2 (1) ◽

pp. 11-21

Author(s):

Silvia Cristini ◽

Giulio Alessandri ◽

Francesco Acerbi ◽

Daniela Tavian ◽

Eugenio A. Parati ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Stem Cell ◽

Cell Function ◽

Self Renewal ◽

Muscle Stem Cells ◽

Skeletal Muscle Stem Cells

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Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

International Journal of Molecular Sciences ◽

10.3390/ijms22020666 ◽

2021 ◽

Vol 22 (2) ◽

pp. 666

Author(s):

Toshio Takahashi

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Function ◽

Cell Activity ◽

Embryonic Stem ◽

Cholinergic Neurons ◽

Cell Types ◽

Proliferative Potential ◽

True Nature ◽

Cholinergic Signaling

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

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Empowering Muscle Stem Cells for the Treatment of Duchenne Muscular Dystrophy

Cells Tissues Organs ◽

10.1159/000514305 ◽

2021 ◽

pp. 1-14

Author(s):

Romina L. Filippelli ◽

Natasha C. Chang

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Cell Function ◽

Critical Role ◽

Membrane Integrity ◽

Muscle Membrane ◽

Muscle Stem Cell ◽

Muscle Stem Cells

Duchenne muscular dystrophy (DMD) is a devastating and debilitating muscle degenerative disease affecting 1 in every 3,500 male births worldwide. DMD is progressive and fatal; accumulated weakening of the muscle tissue leads to an inability to walk and eventual loss of life due to respiratory and cardiac failure. Importantly, there remains no effective cure for DMD. DMD is caused by defective expression of the <i>DMD</i> gene, which encodes for dystrophin, a component of the dystrophin glycoprotein complex. In muscle fibers, this protein complex plays a critical role in maintaining muscle membrane integrity. Emerging studies have shown that muscle stem cells, which are adult stem cells responsible for muscle repair, are also affected in DMD. DMD muscle stem cells do not function as healthy muscle stem cells, and their impairment contributes to disease progression. Deficiencies in muscle stem cell function include impaired establishment of cell polarity leading to defective asymmetric stem cell division, reduced myogenic commitment, impaired differentiation, altered metabolism, and enhanced entry into senescence. Altogether, these findings indicate that DMD muscle stem cells are dysfunctional and have impaired regenerative potential. Although recent advances in adeno-associated vector and antisense oligonucleotide-mediated mechanisms for gene therapy have shown clinical promise, the current therapeutic strategies for muscular dystrophy do not effectively target muscle stem cells and do not address the deficiencies in muscle stem cell function. Here, we discuss the merits of restoring endogenous muscle stem cell function in degenerating muscle as a viable regenerative medicine strategy to mitigate DMD.

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Set1 Targets Genes with Essential Identity and Tumor-Suppressing Functions in Planarian Stem Cells

Genes ◽

10.3390/genes12081182 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1182

Author(s):

Prince Verma ◽

Court K. M. Waterbury ◽

Elizabeth M. Duncan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Mammalian Cells ◽

Cell Function ◽

Genotoxic Stress ◽

Specific Gene ◽

Cell Identity ◽

Chromatin Signature ◽

Lysine Methyltransferase

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 is largely responsible for creating it at both cell identity and putative TSG loci. In addition, we show that depletion of set1 in planarians induces stem cell phenotypes that suggest loss of TSG function, including hyperproliferation and an abnormal DNA damage response (DDR). Importantly, this work establishes that Set1 targets specific gene loci in planarian stem cells and marks them with a conserved chromatin signature. Moreover, our data strongly suggest that Set1 activity at these genes has important functional consequences both during normal homeostasis and in response to genotoxic stress.

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