Exosomes: A Rising Star in Failing Hearts

Xu, Junyan; Chen, Gui-Hao; Yang, Yue-Jin

doi:10.3389/fphys.2017.00494

Cited by 43 publications

(52 citation statements)

References 193 publications

(231 reference statements)

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“…However, LEC treated with DM-Exos didn’t show any significant changes in wound healing rate compared to control, untreated wounded cells. Similar studies have previously explored the role of Exos in cell repair and wound healing in other cell types such as in skin 20 , 33 , 36 , 37 , skeletal 38 and cardiac 39 , 40 muscle. A very recent study has shown that Exos derived from human amniotic epithelial cells promoted wound healing and inhibited scar formation in skin 36 .…”

Section: Discussionmentioning

confidence: 76%

Exosomes from normal and diabetic human corneolimbal keratocytes differentially regulate migration, proliferation and marker expression of limbal epithelial cells

Leszczynska

Kulkarni

Ljubimov

et al. 2018

Sci Rep

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Limbal epithelial stem cells (LESC) maintenance requires communication between stem cells and neighboring stromal keratocytes. Extracellular vesicles (EVs) are important for intercellular communication in various stem cell niches. We explored the regulatory roles of limbal stromal cell (LSC)-derived exosomes (Exos), an EV sub-population, in limbal epithelial cells (LEC) in normal and diabetic limbal niche and determined differences in Exo cargos from normal and diabetic LSC. Wound healing and proliferation rates in primary normal LEC were significantly enhanced upon treatment by normal Exos (N-Exos), but not by diabetic Exos (DM-Exos). Western analysis showed increased Akt phosphorylation in wounded LECs and organ-cultured corneas treated with N-Exos, compared to untreated wounded cells and DM-Exos treated fellow corneas, respectively. N-Exos treated organ-cultured corneas showed upregulation of putative LESC markers, keratin 15 (K15) and Frizzled-7, compared to the DM-Exos treated fellow corneas. By next generation sequencing, we identified differentially expressed small RNAs including microRNAs in DM-Exos vs. N-Exos. Overall, N-Exos have greater effect on LEC proliferation and wound healing than DM-Exos, likely by activating Akt signaling. The small RNA differences in Exos from diabetic vs. normal LSC could contribute to the disease state. Our study suggests that exosomes may serve as novel therapeutic tools for diabetic cornea.

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Section: Discussionmentioning

confidence: 76%

Exosomes from normal and diabetic human corneolimbal keratocytes differentially regulate migration, proliferation and marker expression of limbal epithelial cells

Leszczynska

Kulkarni

Ljubimov

et al. 2018

Sci Rep

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“…These exosomes are currently of major interest with respect to further elucidating cell-cell communication (e.g., Kruger et al, 2014). Specifically, communication through the content of exosomes is considered an important factor for orientation of cells (Xu et al, 2017). Several micro-RNAs, transcription factors and cytokines were identified to be involved in the transfer of epigenetic reprogramming of cells in order to direct them into a specific lineage differentiation.…”

Section: Regulation Of the Differentiation Of Stem Cells In A Living mentioning

confidence: 99%

Fundamentals of Stem Cells: Why and How Patients' Own Adult Stem Cells Are the Next Generation of Medicine

Alt¹,

Schmitz²,

Bai³

2019

Preprint

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Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

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“…The beneficial paracrine effects of transplanted MSCs are, in part, mediated by the release of exosomes. These are extracellular vesicles 30–100 nm in diameter, which contain a variety of molecules, including proteins, miRNA, and mRNA, and thereby play an important role in cell-cell communication [ 213 , 214 ]. Several preclinical studies have demonstrated the benefits of exosome administration in the treatment of CVDs.…”

Section: Strategies To Improve Mscsmentioning

confidence: 99%

Recent Progress in Stem Cell Modification for Cardiac Regeneration

Lemcke

Voronina

Steinhoff

et al. 2018

Stem Cells International

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During the past decades, stem cell-based therapy has acquired a promising role in regenerative medicine. The application of novel cell therapeutics for the treatment of cardiovascular diseases could potentially achieve the ambitious aim of effective cardiac regeneration. Despite the highly positive results from preclinical studies, data from phase I/II clinical trials are inconsistent and the improvement of cardiac remodeling and heart performance was found to be quite limited. The major issues which cardiac stem cell therapy is facing include inefficient cell delivery to the site of injury, accompanied by low cell retention and weak effectiveness of remaining stem cells in tissue regeneration. According to preclinical and clinical studies, various stem cells (adult stem cells, embryonic stem cells, and induced pluripotent stem cells) represent the most promising cell types so far. Beside the selection of the appropriate cell type, researchers have developed several strategies to produce “second-generation” stem cell products with improved regenerative capacity. Genetic and nongenetic modifications, chemical and physical preconditioning, and the application of biomaterials were found to significantly enhance the regenerative capacity of transplanted stem cells. In this review, we will give an overview of the recent developments in stem cell engineering with the goal to facilitate stem cell delivery and to promote their cardiac regenerative activity.

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Exosomes: A Rising Star in Failing Hearts

Cited by 43 publications

References 193 publications

Exosomes from normal and diabetic human corneolimbal keratocytes differentially regulate migration, proliferation and marker expression of limbal epithelial cells

Exosomes from normal and diabetic human corneolimbal keratocytes differentially regulate migration, proliferation and marker expression of limbal epithelial cells

Fundamentals of Stem Cells: Why and How Patients' Own Adult Stem Cells Are the Next Generation of Medicine

Recent Progress in Stem Cell Modification for Cardiac Regeneration

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