Submit to JCM Review for JCM Propose a Special Issue

Journal Menu

Journal Browser

Frontiers in Stem Cell Treatments

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (30 June 2013) | Viewed by 108046

Share This Special Issue

Special Issue Editor

Prof. Dr. Frank Barry

E-Mail Website
Guest Editor

Regenerative Medicine Institute (REMEDI), National Centre of Biomedical Engineering Science(NCBES), National University of Ireland, Galway, Ireland
Interests: biology of adult stem cells; tissue engineering; cell transplantation protocols; immunology of allogeneic cell transplantation; gene therapy; cell-based gene delivery; regulation of differentiation; mechanisms of engraftment and homing of transplanted stem cells; stem cell plasticity

Special Issue Information

Dear Colleagues,

There has been a great deal of interest in recent years in the use of stem cells in the treatment of a broad spectrum of diseases and many predictions have been made which suggest that the future practice of medicine will rely heavily on applications in stem cell technology. There has been steady progress in understanding the biological nature of stem cells, their isolation and expansion, and how they make fate decisions. One of the most significant steps has been the demonstration that mature somatic cells can be reprogrammed to become pluripotent. Indeed, the development of induced pluripotent stem (iPS) cell technology has opened doors into an extraordinary world of new understanding and clinical potential. This great achievement has been justly recognized by the award of the 2012 Nobel Prize in Physiology or Medicine to Sir John B. Gurdon and Shinya Yamanaka.
In addition to progress in understanding the fundamental nature of stem cells, there has also been an explosion of preclinical studies. These have been overwhelmingly positive and have, in study after study, pointed to the therapeutic promise of stem cells. They have taught us about the potential roles of stem cells in tissue regeneration, modulation of the immune system and paracrine mechanisms to stimulate a host response. Nonetheless, the clinical testing of stem cells in controlled, randomized trials has moved at a slow pace and for some the proof of concept is yet to be fully delivered.
There are many obstacles on the road to clinical testing, not least being an understanding of toxicology, mechanism of action and large scale expansion. The current special issue is designed to examine the clinical potential of stem cell therapy and provide a timely update on the current status of clinical trials.

Prof. Dr. Frank Barry
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. Journal of Clinical Medicine 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 2600 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
regenerative medicine
clinical trials
immunomodulation
paracrine effects
pluripotency
mesenchymal stem cells

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (10 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

21 pages, 1542 KiB

Open AccessArticle

Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts

by Matthew M. Cook, Michael R. Doran, Katarina Kollar, Valerie Barbier, Ingrid G. Winkler, Jean-Pierre Levesque, Gary Brooke and Kerry Atkinson

J. Clin. Med. 2013, 2(3), 115-135; https://doi.org/10.3390/jcm2030115 - 23 Sep 2013

Cited by 3 | Viewed by 7470

Abstract

Haematopoietic stem cell (HSC) transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported through co-culture on monolayers of either undifferentiated mesenchymal stromal cells (MSCs) or osteoblasts. Sorted Lineage⁻ Sca-1⁺ c-kit⁺ (LSK) haematopoietic stem/progenitor cells (HPC) demonstrated proliferative capacity on both stromal monolayers with the greatest expansion of LSK shown in cultures supported by osteoblast monolayers. After transplantation, both types of bulk-expanded cultures were capable of engrafting and repopulating lethally irradiated primary and secondary murine recipients. LSKs co-cultured on MSCs showed comparable, but not superior, reconstitution ability to that of freshly isolated LSKs. Surprisingly, however, osteoblast co-cultured LSKs showed significantly poorer haematopoietic reconstitution compared to LSKs co-cultured on MSCs, likely due to a delay in short-term reconstitution. We demonstrated that stromal monolayers can be used to maintain, but not expand, functional HSCs without a need for additional haematopoietic growth factors. We also demonstrated that despite apparently superior in vitro performance, co-injection of bulk cultures of osteoblasts and LSKs in vivo was detrimental to recipient survival and should be avoided in translation to clinical practice. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Figure 1

12 pages, 1078 KiB

Open AccessArticle

Aging Impairs the Proliferative Capacity of Cardiospheres, Cardiac Progenitor Cells and Cardiac Fibroblasts: Implications for Cell Therapy

by Jianqin Ye, Douglas S. Hom, Joy Hwang, Yerem Yeghiazarians, Randall J. Lee and Andrew J. Boyle

J. Clin. Med. 2013, 2(3), 103-114; https://doi.org/10.3390/jcm2030103 - 23 Sep 2013

Cited by 5 | Viewed by 7023

Abstract

Introduction: Cardiospheres (CS) are self-assembling clusters of cells that can be grown from cardiac tissue. They contain a heterogeneous cell population that includes cardiac progenitor cells (CPCs) and cardiac fibroblasts. CS and CPCs have been shown to improve cardiac function after myocardial infarction (MI) in experimental models and are now being studied in clinical trials. The effects of aging on the proliferative capacity of CS and CPCs, and the paracrine signaling between cell types, remain incompletely understood. Methods and Results: We compared the growth of CS from young and aging murine hearts at baseline and following MI. The number of CS from young and aging hearts was similar at baseline. However, after MI, young hearts had a dramatic increase in the number of CS that grew, but this proliferative response to MI was virtually abolished in the aging heart. Further, the proportion of cells within the CS that were CPCs (defined as Sca-1(stem cell antigen-1)⁺/CD45⁻) was significantly lower in aging hearts than young hearts. Thus the number of available CPCs after culture from aging hearts was substantially lower than from young hearts. Cardiac fibroblasts from aging hearts proliferated more slowly in culture than those from young hearts. We then investigated the interaction between aging cardiac fibroblasts and CPCs. We found no significant paracrine effects on proliferation between these cell types, suggesting the impaired proliferation is a cell-autonomous problem. Conclusions: Aging hearts generate fewer CPCs, and aging CPCs have significantly reduced proliferative potential following MI. Aging cardiac fibroblasts also have reduced proliferative capacity, but these appear to be cell-autonomous problems, not caused by paracrine signaling between cell types. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Figure 1

18 pages, 917 KiB

Open AccessArticle

Short Term Culture of Human Mesenchymal Stem Cells with Commercial Osteoconductive Carriers Provides Unique Insights into Biocompatibility

by Matthew B. Murphy, Richard K. Suzuki, Theodore T. Sand, Christopher D. Chaput and Carl A. Gregory

J. Clin. Med. 2013, 2(3), 49-66; https://doi.org/10.3390/jcm2030049 - 19 Aug 2013

Cited by 11 | Viewed by 10793

Abstract

For spinal fusions and the treatment of non-union fractures, biological substrates, scaffolds, or carriers often are applied as a graft to support regeneration of bone. The selection of an appropriate material critically influences cellular function and, ultimately, patient outcomes. Human bone marrow mesenchymal stem cells (BMSCs) are regarded as a critical component of bone healing. However, the interactions of BMSCs and commercial bone matrices are poorly reported. BMSCs were cultured with several commercially available bone substrates (allograft, demineralized bone matrix (DBM), collagen, and various forms of calcium phosphates) for 48 h to understand their response to graft materials during surgical preparation and the first days following implantation (cell retention, gene expression, pH). At 30 and 60 min, bone chips and inorganic substrates supported significantly more cell retention than other materials, while collagen-containing materials became soluble and lost their structure. At 48 h, cells bound to β-tricalcium phosphate-hydroxyapatite (βTCP-HA) and porous hydroxyapatite (HA) granules exhibited osteogenic gene expression statistically similar to bone chips. Through 24 h, the DBM strip and βTCP-collagen became mildly acidic (pH 7.1–7.3), while the DBM poloxamer-putties demonstrated acidity (pH < 5) and the bioglass-containing carrier became basic (pH > 10). The dissolution of DBM and collagen led to a loss of cells, while excessive pH changes potentially diminish cell viability and metabolism. Extracts from DBM-poloxamers induced osteogenic gene expression at 48 h. This study highlights the role that biochemical and structural properties of biomaterials play in cellular function, potentially enhancing or diminishing the efficacy of the overall therapy. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Figure 1

Review

Jump to: Research

15 pages, 241 KiB

Open AccessReview

The Power and the Promise of Cell Reprogramming: Personalized Autologous Body Organ and Cell Transplantation

by Ana Belen Alvarez Palomo, Michaela Lucas, Rodney J. Dilley, Samuel McLenachan, Fred Kuanfu Chen, Jordi Requena, Marti Farrera Sal, Andrew Lucas, Inaki Alvarez, Dolores Jaraquemada and Michael J. Edel

J. Clin. Med. 2014, 3(2), 373-387; https://doi.org/10.3390/jcm3020373 - 4 Apr 2014

Cited by 6 | Viewed by 7616

Abstract

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by the ethical and social questions raised by embryonic stem cells. iPSC technology promises to enable personalized autologous cell therapy and has the potential to revolutionize cell replacement therapy and regenerative medicine. Potential applications of iPSC technology are rapidly increasing in ambition from discrete cell replacement applications to the iPSC assisted bioengineering of body organs for personalized autologous body organ transplant. Recent work has demonstrated that the generation of organs from iPSCs is a future possibility. The development of embryonic-like organ structures bioengineered from iPSCs has been achieved, such as an early brain structure (cerebral organoids), bone, optic vesicle-like structures (eye), cardiac muscle tissue (heart), primitive pancreas islet cells, a tooth-like structure (teeth), and functional liver buds (liver). Thus, iPSC technology offers, in the future, the powerful and unique possibility to make body organs for transplantation removing the need for organ donation and immune suppressing drugs. Whilst it is clear that iPSCs are rapidly becoming the lead cell type for research into cell replacement therapy and body organ transplantation strategies in humans, it is not known whether (1) such transplants will stimulate host immune responses; and (2) whether this technology will be capable of the bioengineering of a complete and fully functional human organ. This review will not focus on reprogramming to iPSCs, of which a plethora of reviews can be found, but instead focus on the latest developments in direct reprogramming of cells, the bioengineering of body organs from iPSCs, and an analysis of the immune response induced by iPSC-derived cells and tissues. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

19 pages, 2030 KiB

Open AccessReview

Towards a Treatment of Stress Urinary Incontinence: Application of Mesenchymal Stromal Cells for Regeneration of the Sphincter Muscle

by Wilhelm K. Aicher, Melanie L. Hart, Jan Stallkamp, Mario Klünder, Michael Ederer, Oliver Sawodny, Martin Vaegler, Bastian Amend, Karl D. Sievert and Arnulf Stenzl

J. Clin. Med. 2014, 3(1), 197-215; https://doi.org/10.3390/jcm3010197 - 24 Feb 2014

Cited by 16 | Viewed by 8488

Abstract

Stress urinary incontinence is a significant social, medical, and economic problem. It is caused, at least in part, by degeneration of the sphincter muscle controlling the tightness of the urinary bladder. This muscular degeneration is characterized by a loss of muscle cells and a surplus of a fibrous connective tissue. In Western countries approximately 15% of all females and 10% of males are affected. The incidence is significantly higher among senior citizens, and more than 25% of the elderly suffer from incontinence. When other therapies, such as physical exercise, pharmacological intervention, or electrophysiological stimulation of the sphincter fail to improve the patient’s conditions, a cell-based therapy may improve the function of the sphincter muscle. Here, we briefly summarize current knowledge on stem cells suitable for therapy of urinary incontinence: mesenchymal stromal cells, urine-derived stem cells, and muscle-derived satellite cells. In addition, we report on ways to improve techniques for surgical navigation, injection of cells in the sphincter muscle, sensors for evaluation of post-treatment therapeutic outcome, and perspectives derived from recent pre-clinical studies. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Graphical abstract

47 pages, 616 KiB

Open AccessReview

Adult Stem Cells and Diseases of Aging

by Lisa B. Boyette and Rocky S. Tuan

J. Clin. Med. 2014, 3(1), 88-134; https://doi.org/10.3390/jcm3010088 - 21 Jan 2014

Cited by 71 | Viewed by 18729

Abstract

Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Figure 1

49 pages, 877 KiB

Open AccessReview

Stem Cells on Biomaterials for Synthetic Grafts to Promote Vascular Healing

by Patrick Babczyk, Clelia Conzendorf, Jens Klose, Margit Schulze, Kathrin Harre and Edda Tobiasch

J. Clin. Med. 2014, 3(1), 39-87; https://doi.org/10.3390/jcm3010039 - 15 Jan 2014

Cited by 18 | Viewed by 12605

Abstract

This review is divided into two interconnected parts, namely a biological and a chemical one. The focus of the first part is on the biological background for constructing tissue-engineered vascular grafts to promote vascular healing. Various cell types, such as embryonic, mesenchymal and induced pluripotent stem cells, progenitor cells and endothelial- and smooth muscle cells will be discussed with respect to their specific markers. The in vitro and in vivo models and their potential to treat vascular diseases are also introduced. The chemical part focuses on strategies using either artificial or natural polymers for scaffold fabrication, including decellularized cardiovascular tissue. An overview will be given on scaffold fabrication including conventional methods and nanotechnologies. Special attention is given to 3D network formation via different chemical and physical cross-linking methods. In particular, electron beam treatment is introduced as a method to combine 3D network formation and surface modification. The review includes recently published scientific data and patents which have been registered within the last decade. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Graphical abstract

26 pages, 382 KiB

Open AccessReview

The Regenerative Role of the Fetal and Adult Stem Cell Secretome

by Sveva Bollini, Chiara Gentili, Roberta Tasso and Ranieri Cancedda

J. Clin. Med. 2013, 2(4), 302-327; https://doi.org/10.3390/jcm2040302 - 17 Dec 2013

Cited by 61 | Viewed by 12420

Abstract

For a long time, the stem cell regenerative paradigm has been based on the assumption that progenitor cells play a critical role in tissue repair by means of their plasticity and differentiation potential. However, recent works suggest that the mechanism underlying the benefits of stem cell transplantation might relate to a paracrine modulatory effect rather than the replacement of affected cells at the site of injury. Therefore, mounting evidence that stem cells may act as a reservoir of trophic signals released to modulate the surrounding tissue has led to a paradigm shift in regenerative medicine. Attention has been shifted from analysis of the stem cell genome to understanding the stem cell “secretome”, which is represented by the growth factors, cytokines and chemokines produced through paracrine secretion. Insights into paracrine-mediated repair support a new approach in regenerative medicine and the isolation and administration of specific stem cell-derived paracrine factors may represent an extremely promising strategy, introducing paracrine-based therapy as a novel and feasible clinical application. In this review, we will discuss the regenerative potential of fetal and adult stem cells, with particular attention to their secretome. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Graphical abstract

22 pages, 351 KiB

Open AccessReview

An Update on Translating Stem Cell Therapy for Stroke from Bench to Bedside

by Travis Dailey, Christopher Metcalf, Yusef I. Mosley, Robert Sullivan, Kazutaka Shinozuka, Naoki Tajiri, Mibel Pabon, Sandra Acosta, Yuji Kaneko, Harry Van Loveren and Cesar V. Borlongan

J. Clin. Med. 2013, 2(4), 220-241; https://doi.org/10.3390/jcm2040220 - 1 Nov 2013

Cited by 27 | Viewed by 10718

Abstract

With a constellation of stem cell sources available, researchers hope to utilize their potential for cellular repair as a therapeutic target for disease. However, many lab-to-clinic translational considerations must be given in determining their efficacy, variables such as the host response, effects on native tissue, and potential for generating tumors. This review will discuss the current knowledge of stem cell research in neurological disease, mainly stroke, with a focus on the benefits, limitations, and clinical potential. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Graphical abstract

13 pages, 441 KiB

Open AccessReview

Mesenchymal Stromal Cells: Updates and Therapeutic Outlook in Rheumatic Diseases

by Yves-Marie Pers and Christian Jorgensen

J. Clin. Med. 2013, 2(4), 201-213; https://doi.org/10.3390/jcm2040201 - 23 Oct 2013

Cited by 5 | Viewed by 10939

Abstract

Multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs) are adult stem cells exhibiting functional properties that have opened the way for cell-based clinical therapies. MSCs have been reported to exhibit immunosuppressive as well as healing properties, improving angiogenesis and preventing apoptosis or fibrosis through the secretion of paracrine mediators. This review summarizes recent progress on the clinical application of stem cells therapy in some inflammatory and degenerative rheumatic diseases. To date, most of the available data have been obtained in preclinical models and clinical efficacy needs to be evaluated through controlled randomized double-blind trials. Full article

(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)

► Show Figures

Journal Menu

Journal Browser

Frontiers in Stem Cell Treatments

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (10 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI