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Mesenchymal Stem Cells and Their Derived Products in Aging and Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 12630

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Dr. Noemi Eiro Diaz

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Guest Editor

Research Unit, Hospital Fundación de Jove, Avda. Eduardo de Castro 161, 33290 Gijón, Spain
Interests: mesenchymal stem cells; conditioned medium; secretome; breast cancer; prostate cancer; metalloproteinases; stroma, fibroblasts; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

Dr. Francisco J. Vizoso

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Co-Guest Editor

1. Unidad de Investigación, Fundación Hospital de Jove, 33290 Gijón, Spain
2. Fundación para la Investigación con Células Madre Uterinas (FICEMU), 33212 Gijón, Spain
Interests: mesenchymal stem cell
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesenchymal stem/stromal cells (MSC) play an increasingly evident role in tissue homeostasis through a complex signalling network. Directly (by contact) or indirectly (via the secretome or extracellular vesicles), MSCs show anti-inflammatory, anti-oxidative stress, pro-angiogenic, anti-tumour, anti-fibrotic and anti-microbial effects, among others, depending on the tissue from which they originate. Research shows that MSC-derived products have the same biological effects as their progenitor cells, with advantages in safety, handling and use. MSC-derived products are thus establishing themselves as potential future therapies of cell-free biological and regenerative medicine.

It is of particular interest to learn and understand the effect of MSCs and especially their derivatives on aging and its associated pathological processes such as cancer, degenerative processes, oxidative stress, etc.

Therefore, we encourage you to contribute to this Special Issue with your work to establish the basis for a new therapeutic concept that can respond to the needs of patients.

Dr. Noemi Eiro
Dr. Francisco J. Vizoso
Guest Editors

Manuscript Submission Information

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Published Papers (5 papers)

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Research

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18 pages, 6598 KiB

Open AccessArticle

Regulation of Immune Checkpoint Antigen CD276 (B7-H3) on Human Placenta-Derived Mesenchymal Stromal Cells in GMP-Compliant Cell Culture Media

by Bastian Amend, Lea Buttgereit, Tanja Abruzzese, Niklas Harland, Harald Abele, Peter Jakubowski, Arnulf Stenzl, Raphael Gorodetsky and Wilhelm K. Aicher

Int. J. Mol. Sci. 2023, 24(22), 16422; https://doi.org/10.3390/ijms242216422 - 16 Nov 2023

Viewed by 765

Abstract

Therapies utilizing autologous mesenchymal cell delivery are being investigated as anti-inflammatory and regenerative treatments for a broad spectrum of age-related diseases, as well as various chronic and acute pathological conditions. Easily available allogeneic full-term human placenta mesenchymal stromal cells (pMSCs) were used as a potential pro-regenerative, cell-based therapy in degenerative diseases, which could be applied also to elderly individuals. To explore the potential of allogeneic pMSCs transplantation for pro-regenerative applications, such cells were isolated from five different term-placentas, obtained from the dissected maternal, endometrial (mpMSCs), and fetal chorion tissues (fpMSCs), respectively. The proliferation rate of the cells in the culture, as well as their shape, in vitro differentiation potential, and the expression of mesenchymal lineage and stem cell markers, were investigated. Moreover, we studied the expression of immune checkpoint antigen CD276 as a possible modulation of the rejection of transplanted non-HLA-matched homologous or even xeno-transplanted pMSCs. The expression of the cell surface markers was also explored in parallel in the cryosections of the relevant intact placenta tissue samples. The expansion of pMSCs in a clinical-grade medium complemented with 5% human platelet lysate and 5% human serum induced a significant expression of CD276 when compared to mpMSCs expanded in a commercial medium. We suggest that the expansion of mpMSCs, especially in a medium containing platelet lysate, elevated the expression of the immune-regulatory cell surface marker CD276. This may contribute to the immune tolerance towards allogeneic pMSC transplantations in clinical situations and even in xenogenic animal models of human diseases. The endurance of the injected comparably young human-term pMSCs may promote prolonged effects in clinical applications employing non-HLA-matched allogeneic cell therapy for various degenerative disorders, especially in aged adults. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells and Their Derived Products in Aging and Diseases)

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16 pages, 1836 KiB

Open AccessArticle

Allogenic Adipose-Derived Stem Cells in Diabetic Foot Ulcer Treatment: Clinical Effectiveness, Safety, Survival in the Wound Site, and Proteomic Impact

by Beata Mrozikiewicz-Rakowska, Ilona Szabłowska-Gadomska, Dominik Cysewski, Stefan Rudziński, Rafał Płoski, Piotr Gasperowicz, Magdalena Konarzewska, Jakub Zieliński, Mateusz Mieczkowski, Damian Sieńko, Tomasz Grzela, Maria Noszczyk, Barbara Paleska, Leszek Czupryniak and Malgorzata Lewandowska-Szumiel

Int. J. Mol. Sci. 2023, 24(2), 1472; https://doi.org/10.3390/ijms24021472 - 12 Jan 2023

Cited by 3 | Viewed by 4198

Abstract

Although encouraging results of adipose-derived stem cell (ADSC) use in wound healing are available, the mechanism of action has been studied mainly in vitro and in animals. This work aimed to examine the safety and efficacy of allogenic ADSCs in human diabetic foot ulcer treatment, in combination with the analyses of the wound. Equal groups of 23 participants each received fibrin gel with ADSCs or fibrin gel alone. The clinical effects were assessed at four time points: days 7, 14, 21 and 49. Material collected during debridement from a subset of each group was analyzed for the presence of ADSC donor DNA and proteomic changes. The reduction in wound size was greater at all subsequent visits, significantly on day 21 and 49, and the time to 50% reduction in the wound size was significantly shorter in patients who received ADSCs. Complete healing was achieved at the end of the study in seven patients treated with ADSCs vs. one treated without ADSCs. One week after ADSC application, 34 proteins significantly differentiated the material from both groups, seven of which, i.e., GAPDH, CAT, ACTN1, KRT1, KRT9, SCL4A1, and TPI, positively correlated with the healing rate. We detected ADSC donor DNA up to 21 days after administration. We confirmed ADSC-related improvement in wound healing that correlated with the molecular background, which provides insights into the role of ADSCs in wound healing—a step toward the development of cell-based therapies. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells and Their Derived Products in Aging and Diseases)

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19 pages, 4398 KiB

Open AccessArticle

iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs

by Hae-Ri Lee, Soo Kim, Sungho Shin, Seon-Yeong Jeong, Dae-Won Lee, Sun-Ung Lim, Ji Yeon Kang, Mi-Young Son, Cheolju Lee, Kyung-Rok Yu, Myungshin Kim and Il-Hoan Oh

Int. J. Mol. Sci. 2023, 24(1), 881; https://doi.org/10.3390/ijms24010881 - 03 Jan 2023

Cited by 6 | Viewed by 3309

Abstract

Mesenchymal stromal cells derived from induced pluripotent stem cells (iMSCs) have been proposed as alternative sources of primary MSCs with various advantages for cell therapeutic trials. However, precise evaluation of the differences between iMSCs and primary MSCs is lacking due to individual variations in the donor cells, which obscure direct comparisons between the two. In this study, we generated donor-matched iMSCs from individual bone marrow-derived MSCs and directly compared their cell-autonomous and paracrine therapeutic effects. We found that the transition from primary MSCs to iMSCs is accompanied by a functional shift towards higher proliferative activity, with variations in differentiation potential in a donor cell-dependent manner. The transition from MSCs to iMSCs was associated with common changes in transcriptomic and proteomic profiles beyond the variations of their individual donors, revealing expression patterns unique for the iMSCs. These iMSC-specific patterns were characterized by a shift in cell fate towards a pericyte-like state and enhanced secretion of paracrine cytokine/growth factors. Accordingly, iMSCs exhibited higher support for the self-renewing expansion of primitive hematopoietic progenitors and more potent immune suppression of allogenic immune responses than MSCs. Our study suggests that iMSCs represent a separate entity of MSCs with unique therapeutic potential distinct from their parental MSCs, but points to the need for iMSC characterization in the individual basis. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells and Their Derived Products in Aging and Diseases)

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Review

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13 pages, 1125 KiB

Open AccessReview

Revolutionizing Radiotoxicity Management with Mesenchymal Stem Cells and Their Derivatives: A Focus on Radiation-Induced Cystitis

by Carole Helissey, Sophie Cavallero, Nathalie Guitard, Hélène Théry, Cyrus Chargari and Sabine François

Int. J. Mol. Sci. 2023, 24(10), 9068; https://doi.org/10.3390/ijms24109068 - 22 May 2023

Viewed by 1582

Abstract

Although radiation therapy plays a crucial role in cancer treatment, and techniques have improved continuously, irradiation induces side effects in healthy tissue. Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers and negatively impacts patients’ quality of life (QoL). To date, no effective treatment is available, and this toxicity remains a therapeutic challenge. In recent times, stem cell-based therapy, particularly the use of mesenchymal stem cells (MSC), has gained attention in tissue repair and regeneration due to their easy accessibility and their ability to differentiate into several tissue types, modulate the immune system and secrete substances that help nearby cells grow and heal. In this review, we will summarize the pathophysiological mechanisms of radiation-induced injury to normal tissues, including radiation cystitis (RC). We will then discuss the therapeutic potential and limitations of MSCs and their derivatives, including packaged conditioned media and extracellular vesicles, in the management of radiotoxicity and RC. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells and Their Derived Products in Aging and Diseases)

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12 pages, 595 KiB

Open AccessReview

Mesenchymal-Stromal-Cell-Conditioned Media and Their Implication for Osteochondral Regeneration

by Dana Ivanisova, Martin Bohac, Martina Culenova, Veronika Smolinska and Lubos Danisovic

Int. J. Mol. Sci. 2023, 24(10), 9054; https://doi.org/10.3390/ijms24109054 - 21 May 2023

Cited by 3 | Viewed by 2195

Abstract

Despite significant advances in biomedical research, osteochondral defects resulting from injury, an autoimmune condition, cancer, or other pathological conditions still represent a significant medical problem. Even though there are several conservative and surgical treatment approaches, in many cases, they do not bring the expected results and further permanent damage to the cartilage and bones occurs. Recently, cell-based therapies and tissue engineering have gradually become promising alternatives. They combine the use of different types of cells and biomaterials to induce regeneration processes or replace damaged osteochondral tissue. One of the main challenges of this approach before clinical translation is the large-scale in vitro expansion of cells without changing their biological properties, while the use of conditioned media which contains various bioactive molecules appears to be very important. The presented manuscript provides a review of the experiments focused on osteochondral regeneration by using conditioned media. In particular, the effect on angiogenesis, tissue healing, paracrine signaling, and enhancing the properties of advanced materials are pointed out. Full article

(This article belongs to the Special Issue Mesenchymal Stem Cells and Their Derived Products in Aging and Diseases)

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