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Cells
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Adult Stem Cells and Exosomes for Regenerative Therapy
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Adult Stem Cells and Exosomes for Regenerative Therapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (15 June 2021) | Viewed by 26813

Special Issue Editor

Prof. Dr. Johnson Rajasingh

E-Mail Website
Guest Editor
Department of Bioscience Research, Department of Medicine, Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN, USA
Interests: generation of cardiomyocytes from induced pluripotent stem cells and its therapeutic potential in repairing ischemic heart; lungs and injured bones

Special Issue Information

Dear Colleagues,

Stem cells are a rare population of undifferentiated cells present in every organ and can be activated to proliferate and differentiate into the required type of cells upon the loss of cells or injury to the tissue. Stem cell therapy, including induced pluripotent stem cells, has been identified as effective therapy to regenerate injured tissues. Innovative preclinical and clinical studies on stem cell therapies have created exciting possibilities for repairing injuries in various organs and improving quality of life. Recent advances in biomedical research have revealed that not the stem cells, but the paracrine factors secreted in the form of small vesicles, called exosomes, by the stem cells are playing a major role in regenerative medicine. In this Special Issue, we will focus on how stem cells and their nanosize secretory vesicles have been utilized for the regenerative therapy.

Prof. Johnson Rajasingh
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stem cells
  • exosomes
  • biomarkers
  • regeneratve medicine
  • therapeutic agents
  • induced pluripotent stem cells

Published Papers (5 papers)

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Research

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15 pages, 3543 KiB  
Article
Generation and Evaluation of Isogenic iPSC as a Source of Cell Replacement Therapies in Patients with Kearns Sayre Syndrome
by Glen Lester Sequiera, Abhay Srivastava, Keshav Narayan Alagarsamy, Cheryl Rockman-Greenberg and Sanjiv Dhingra
Cells 2021, 10(3), 568; https://doi.org/10.3390/cells10030568 - 5 Mar 2021
Cited by 11 | Viewed by 2946
Abstract
Kearns Sayre syndrome (KSS) is mitochondrial multisystem disorder with no proven effective treatment. The underlying cause for multisystem involvement is the energy deficit resulting from the load of mutant mitochondrial DNA (mtDNA), which manifests as loss of cells and tissue dysfunction. Therefore, functional [...] Read more.
Kearns Sayre syndrome (KSS) is mitochondrial multisystem disorder with no proven effective treatment. The underlying cause for multisystem involvement is the energy deficit resulting from the load of mutant mitochondrial DNA (mtDNA), which manifests as loss of cells and tissue dysfunction. Therefore, functional organ or cellular replacement provides a promising avenue as a therapeutic option. Patient-specific induced pluripotent stem cells (iPSC) have become a handy tool to create personalized cell -based therapies. iPSC are capable of self-renewal, differentiation into all types of body cells including cardiomyocytes (CM) and neural progenitor cells (NPC). In KSS patients, mutations in mtDNA are largely found in the muscle tissue and are predominantly absent in the blood cells. Therefore, we conceptualized that peripheral blood mononuclear cells (PBMNC) from KSS patients can be reprogrammed to generate mutation free, patient specific iPSC lines that can be used as isogenic source of cell replacement therapies to treat affected organs. In the current study we generated iPSC lines from two female patients with clinical diagnosis of classic KSS. Our data demonstrate that iPSC from these KSS patients showed normal differentiation potential toward CM, NPC and fibroblasts without any mtDNA deletions over passages. Next, we also found that functional studies including ATP production, reactive oxygen species generation, lactate accumulation and mitochondrial membrane potential in iPSC, CM, NPC and fibroblasts of these KSS patients were not different from respective cells from healthy controls. PBMNCs from these KSS patients in the current study did not reproduce mtDNA mutations which were present in muscle biopsies. Furthermore, we demonstrate for the first time that this phenomenon provides opportunities to create isogenic mutation free iPSC with absent or very low level of expression of mtDNA deletion which can be banked for future cell replacement therapies in these patients as the disease progresses. Full article
(This article belongs to the Special Issue Adult Stem Cells and Exosomes for Regenerative Therapy)
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Review

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17 pages, 807 KiB  
Review
Intestinal Stem Cell Development in the Neonatal Gut: Pathways Regulating Development and Relevance to Necrotizing Enterocolitis
by Aparna Venkatraman, Wei Yu, Christopher Nitkin and Venkatesh Sampath
Cells 2021, 10(2), 312; https://doi.org/10.3390/cells10020312 - 3 Feb 2021
Cited by 6 | Viewed by 3533
Abstract
The intestine is extremely dynamic and the epithelial cells that line the intestine get replaced every 3–5 days by highly proliferative intestinal stem cells (ISCs). The instructions for ISCs to self-renew or to differentiate come as cues from their surrounding microenvironment or their [...] Read more.
The intestine is extremely dynamic and the epithelial cells that line the intestine get replaced every 3–5 days by highly proliferative intestinal stem cells (ISCs). The instructions for ISCs to self-renew or to differentiate come as cues from their surrounding microenvironment or their niche. A small number of evolutionarily conserved signaling pathways act as a critical regulator of the stem cells in the adult intestine, and these pathways are well characterized. However, the mechanisms, nutritional, and environmental signals that help establish the stem cell niche in the neonatal intestine are less studied. Deciphering the key signaling pathways that regulate the development and maintenance of the stem cells is particularly important to understanding how the intestine regenerates from necrotizing enterocolitis, a devastating disease in newborn infants characterized by inflammation, tissues necrosis, and stem cell injury. In this review, we piece together current knowledge on morphogenetic and immune pathways that regulate intestinal stem cell in neonates and highlight how the cross talk among these pathways affect tissue regeneration. We further discuss how these key pathways are perturbed in NEC and review the scientific knowledge relating to options for stem cell therapy in NEC gleaned from pre-clinical experimental models of NEC. Full article
(This article belongs to the Special Issue Adult Stem Cells and Exosomes for Regenerative Therapy)
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14 pages, 2423 KiB  
Review
Role of Human Mesenchymal Stem Cells in Regenerative Therapy
by Jayavardini Vasanthan, Narasimman Gurusamy, Sheeja Rajasingh, Vinoth Sigamani, Shivaani Kirankumar, Edwin L. Thomas and Johnson Rajasingh
Cells 2021, 10(1), 54; https://doi.org/10.3390/cells10010054 - 31 Dec 2020
Cited by 62 | Viewed by 10705
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells which can proliferate and replace dead cells in the body. MSCs also secrete immunomodulatory molecules, creating a regenerative microenvironment that has an excellent potential for tissue regeneration. MSCs can be easily isolated and grown in vitro [...] Read more.
Mesenchymal stem cells (MSCs) are multipotent cells which can proliferate and replace dead cells in the body. MSCs also secrete immunomodulatory molecules, creating a regenerative microenvironment that has an excellent potential for tissue regeneration. MSCs can be easily isolated and grown in vitro for various applications. For the past two decades, MSCs have been used in research, and many assays and tests have been developed proving that MSCs are an excellent cell source for therapy. This review focusses on quality control parameters required for applications of MSCs including colony formation, surface markers, differentiation potentials, and telomere length. Further, the specific mechanisms of action of MSCs under various conditions such as trans-differentiation, cell fusion, mitochondrial transfer, and secretion of extracellular vesicles are discussed. This review aims to underline the applications and benefits of MSCs in regenerative medicine and tissue engineering. Full article
(This article belongs to the Special Issue Adult Stem Cells and Exosomes for Regenerative Therapy)
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17 pages, 2105 KiB  
Review
Stem Cell Metabolism: Powering Cell-Based Therapeutics
by Vagner O. C. Rigaud, Robert Hoy, Sadia Mohsin and Mohsin Khan
Cells 2020, 9(11), 2490; https://doi.org/10.3390/cells9112490 - 16 Nov 2020
Cited by 26 | Viewed by 4594
Abstract
Cell-based therapeutics for cardiac repair have been extensively used during the last decade. Preclinical studies have demonstrated the effectiveness of adoptively transferred stem cells for enhancement of cardiac function. Nevertheless, several cell-based clinical trials have provided largely underwhelming outcomes. A major limitation is [...] Read more.
Cell-based therapeutics for cardiac repair have been extensively used during the last decade. Preclinical studies have demonstrated the effectiveness of adoptively transferred stem cells for enhancement of cardiac function. Nevertheless, several cell-based clinical trials have provided largely underwhelming outcomes. A major limitation is the lack of survival in the harsh cardiac milieu as only less than 1% donated cells survive. Recent efforts have focused on enhancing cell-based therapeutics and understanding the biology of stem cells and their response to environmental changes. Stem cell metabolism has recently emerged as a critical determinant of cellular processes and is uniquely adapted to support proliferation, stemness, and commitment. Metabolic signaling pathways are remarkably sensitive to different environmental signals with a profound effect on cell survival after adoptive transfer. Stem cells mainly generate energy through glycolysis while maintaining low oxidative phosphorylation (OxPhos), providing metabolites for biosynthesis of macromolecules. During commitment, there is a shift in cellular metabolism, which alters cell function. Reprogramming stem cell metabolism may represent an attractive strategy to enhance stem cell therapy for cardiac repair. This review summarizes the current literature on how metabolism drives stem cell function and how this knowledge can be applied to improve cell-based therapeutics for cardiac repair. Full article
(This article belongs to the Special Issue Adult Stem Cells and Exosomes for Regenerative Therapy)
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17 pages, 1199 KiB  
Review
Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies
by Sherin Saheera, Ajay Godwin Potnuri and Prasanna Krishnamurthy
Cells 2020, 9(9), 1974; https://doi.org/10.3390/cells9091974 - 26 Aug 2020
Cited by 25 | Viewed by 4338
Abstract
Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range [...] Read more.
Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell–cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections. Full article
(This article belongs to the Special Issue Adult Stem Cells and Exosomes for Regenerative Therapy)
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