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Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases
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Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 30119

Special Issue Editor

Prof. Dr. Wilhelm K. Aicher

E-Mail Website
Guest Editor
Department of Urology, University of Tuebingen Hospital, Waldhoernlestr 22, D-72072 Tubingen, Germany
Interests: cell therapy; mesenchymal stromal cells; organoids; preclinical animal models in urology; bladder cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stress urinary incontinence is associated with a loss of contraction force or control of the urethral sphincter muscle. This may be caused by injury of lower pelvic floor tissue or its nerve supply (e.g., through vaginal delivery or by surgery), age-related loss of muscle cells and myofibres, changes in tissue elasticity associated with hormonal changes in menopause and other reasons. In Western countries, overall, about 13% of the population suffer from urinary incontinence. This propels expenses for management and treatment to the top levels of annual costs for both healthcare insurance enterprises and affected individuals. Conservative treatment options for patients suffering from incontinence include physical muscle exercise, sometimes in combination with electrophysical stimulation, and pharmacological intervention. If these therapies fail to satisfy the patient or insufficiently improve the situation, surgical intervention may help. However, surgery in most cases only improves the sequela of incontinence but does not cure the cause of it, i.e., loss of muscle function by loss of either innervation or contractile muscle tissue.

Rehabilitation of the contractile muscle function by injection of regeneration-facilitating cells is the key challenge of cell-based therapy for stress urinary incontinence. In this Special Issue, we discuss several aspects of cell therapies for urinary incontinence. We introduce our readers to the clinical problem, report on the latest development of pre-clinical animal studies and discuss several technical issues, including animal serum-free production of cells under good manufacturing practice (GMP) conditions, selection of suitable biomaterials and requirement for bioreactors to upscale cell production for clinical situations. We introduce the readers to a novel technology to inject cells by a waterjet instead of needles and report on the latest development of recent as well as current clinical feasibility studies of cell therapies.

We complement this Special Issue with an overview of cell therapy for the heart and discuss possibilities to replace, at least in some situations, autologous cell therapy with homologous cell applications. In addition, we invite other authors to offer their expertise in cell-based therapies for age-related disorders.

Prof. Dr. Wilhelm K. Aicher
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Stress urinary incontinence
  • Cell therapy
  • Pre-clinical studies
  • GMP cell production

Published Papers (6 papers)

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Research

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16 pages, 7004 KiB  
Article
Novel Techniques to Improve Precise Cell Injection
by Walter Linzenbold, Andreas Fech, Manuela Hofmann, Wilhelm K. Aicher and Markus D. Enderle
Int. J. Mol. Sci. 2021, 22(12), 6367; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126367 - 14 Jun 2021
Cited by 2 | Viewed by 1737
Abstract
We noted recently that the injection of cells with a needle through a cystoscope in the urethral sphincter muscle of pigs failed to deposit them nearby or at the intended target position in about 50% of all animals investigated (n > 100). [...] Read more.
We noted recently that the injection of cells with a needle through a cystoscope in the urethral sphincter muscle of pigs failed to deposit them nearby or at the intended target position in about 50% of all animals investigated (n > 100). Increasing the chance for precise cell injection by shotgun approaches employing several circumferential injections into the sphincter muscle bears the risk of tissue injury. In this study, we developed and tested a novel needle-free technique to precisely inject cells in the urethral sphincter tissue, or other tissues, using a water-jet system. This system was designed to fit in the working channels of endoscopes and cystoscopes, allowing a wide range of minimally invasive applications. We analyze key features, including the physical parameters of the injector design, pressure ranges applicable for tissue penetration and cell injections and biochemical parameters, such as different compositions of injection media. Our results present settings that enable the high viability of cells post-injection. Lastly, the method is suitable to inject cells in the superficial tissue layer and in deeper layers, required when the submucosa or the sphincter muscle of the urethra is targeted. Full article
(This article belongs to the Special Issue Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases)
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17 pages, 801 KiB  
Article
Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances, Challenges and Future Prospects
by Florian A. Schmid, J. Koudy Williams, Thomas M. Kessler, Arnulf Stenzl, Wilhelm K. Aicher, Karl-Erik Andersson and Daniel Eberli
Int. J. Mol. Sci. 2021, 22(8), 3981; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083981 - 12 Apr 2021
Cited by 14 | Viewed by 4468
Abstract
Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and [...] Read more.
Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges. Full article
(This article belongs to the Special Issue Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases)
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Review

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13 pages, 2462 KiB  
Review
Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence
by Bastian Amend, Niklas Harland, Jasmin Knoll, Arnulf Stenzl and Wilhelm K. Aicher
Int. J. Mol. Sci. 2021, 22(11), 6092; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116092 - 05 Jun 2021
Cited by 4 | Viewed by 4201
Abstract
Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or [...] Read more.
Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI. Full article
(This article belongs to the Special Issue Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases)
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28 pages, 2542 KiB  
Review
Current Strategies for the Regeneration of Skeletal Muscle Tissue
by Emine Alarcin, Ayca Bal-Öztürk, Hüseyin Avci, Hamed Ghorbanpoor, Fatma Dogan Guzel, Ali Akpek, Gözde Yesiltas, Tuba Canak-Ipek and Meltem Avci-Adali
Int. J. Mol. Sci. 2021, 22(11), 5929; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115929 - 31 May 2021
Cited by 31 | Viewed by 7287
Abstract
Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To [...] Read more.
Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To promote muscle repair and regeneration, various strategies for skeletal muscle tissue engineering have been developed in the last decades. However, there is still a high demand for the development of new methods and materials that promote skeletal muscle repair and functional regeneration to bring approaches closer to therapies in the clinic that structurally and functionally repair muscle. The combination of stem cells, biomaterials, and biomolecules is used to induce skeletal muscle regeneration. In this review, we provide an overview of different cell types used to treat skeletal muscle injury, highlight current strategies in biomaterial-based approaches, the importance of topography for the successful creation of functional striated muscle fibers, and discuss novel methods for muscle regeneration and challenges for their future clinical implementation. Full article
(This article belongs to the Special Issue Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases)
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23 pages, 21075 KiB  
Review
Allogenic Use of Human Placenta-Derived Stromal Cells as a Highly Active Subtype of Mesenchymal Stromal Cells for Cell-Based Therapies
by Raphael Gorodetsky and Wilhelm K. Aicher
Int. J. Mol. Sci. 2021, 22(10), 5302; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105302 - 18 May 2021
Cited by 19 | Viewed by 5836
Abstract
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and [...] Read more.
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies. Full article
(This article belongs to the Special Issue Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases)
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14 pages, 1803 KiB  
Review
Human Platelet Lysate for Good Manufacturing Practice-Compliant Cell Production
by Michaela Oeller, Sandra Laner-Plamberger, Linda Krisch, Eva Rohde, Dirk Strunk and Katharina Schallmoser
Int. J. Mol. Sci. 2021, 22(10), 5178; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105178 - 13 May 2021
Cited by 28 | Viewed by 5784
Abstract
Numerous cell-based therapeutics are currently being tested in clinical trials. Human platelet lysate (HPL) is a valuable alternative to fetal bovine serum as a cell culture medium supplement for a variety of different cell types. HPL as a raw material permits animal serum-free [...] Read more.
Numerous cell-based therapeutics are currently being tested in clinical trials. Human platelet lysate (HPL) is a valuable alternative to fetal bovine serum as a cell culture medium supplement for a variety of different cell types. HPL as a raw material permits animal serum-free cell propagation with highly efficient stimulation of cell proliferation, enabling humanized manufacturing of cell therapeutics within a reasonable timeframe. Providers of HPL have to consider dedicated quality issues regarding identity, purity, potency, traceability and safety. Release criteria have to be defined, characterizing the suitability of HPL batches for the support of a specific cell culture. Fresh or expired platelet concentrates from healthy blood donors are the starting material for HPL preparation, according to regulatory requirements. Pooling of individual platelet lysate units into one HPL batch can balance donor variation with regard to essential platelet-derived growth factors and cytokines. The increasingly applied pathogen reduction technologies will further increase HPL safety. In this review article, aspects and regulatory requirements of whole blood donation and details of human platelet lysate manufacturing are presented. International guidelines for raw materials are discussed, and defined quality controls, as well as release criteria for safe and GMP-compliant HPL production, are summarized. Full article
(This article belongs to the Special Issue Cell Therapy for Stress Urinary Incontinence and Other Age-Related Diseases)
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