Therapeutic mechanisms and routes of delivery of mesenchymal stem cells in veterinary medicine: A point of view

Mesenchymal stem cells (MSCs) have been isolated from the endometrium of humans, mice, cows, pigs and ewes. Typically, these cells are detected in the deep regions of the endometrium, closer to the union with the myometrium. MSCs possess characteristics such as clonogenicity and multipotentiality since they can differentiate in vitro into adipogenic, chondrogenic and osteogenic lineages. These cells can be induced to differentiate in vitro not only into the mesodermal lineage but also into the endodermal and ectodermal lineages. Therefore, MSCs show a great regenerative capacity for various organs and tissues, including the endometrium. Some advantages of endometrial MSCs compared with other MSC sources are their immune modulating activity, their ease of obtainment, and the amount of sample that may be collected. The study of endometrial MSCs in domestic animals is a new and promising field because increasing our understanding of the physiology and biology of these cells may lead to a better understanding of the physiopathology of reproductive diseases, and the development of treatment methods for infertility problems. In other veterinary medicine fields, MSCs can be used for the treatment of autoimmune diseases, cardiac affections, musculoskeletal and articular lesions, muscle degeneration, type 1 diabetes, urinary tract diseases, neurodegenerative processes and tumours. Finally, MSCs are also an important clinical tool for tissue engineering and regenerative medicine. The aim of this review is to present an updated outlook of the knowledge regarding endometrial MSCs and their possible applications in veterinary medicine.Figure 1: Immunoregulatory ability of MSCs. MSCs regulate the functions of NK cells, dendritic cells (DC) and T lymphocytes. The immunosuppressive effect may occur through the secretion of different factors or through cellular contact (black arrows). The former pathway involves TGFß, HGF, IL-10, PGE2, and HLA-G5, whereas the latter pathway involves the products of IDO enzyme activity, PD-L1, HLA-G1, ICAM-I and VCAM-I. Pro-inflammatory cytokines (IFN-?) secreted by NK cells and activated T lymphocytes favour the immunoregulatory activity of MSCs (dotted lines), because they increase or induce the secretion of molecules that regulate the functions of the distinct cellular components of the immune system. Modified from Montesinos et al, and Ma et al.19,66

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Current Status of Canine Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Veterinary Medicine

Stem Cells International ◽

10.1155/2018/8329174 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 7

Author(s):

Tania Sultana ◽

Soojung Lee ◽

Hun-Young Yoon ◽

Jeong Ik Lee

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Veterinary Medicine ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Ethical Issues ◽

Treatment Strategies ◽

Current Status

Stem cell therapy has prompted the expansion of veterinary medicine both experimentally and clinically, with the potential to contribute to contemporary treatment strategies for various diseases and conditions for which limited or no therapeutic options are presently available. Although the application of various types of stem cells, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose tissue-derived mesenchymal stem cells (AT-MSCs), and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), has promising potential to improve the health of different species, it is crucial that the benefits and drawbacks are completely evaluated before use. Umbilical cord blood (UCB) is a rich source of stem cells; nonetheless, isolation of mesenchymal stem cells (MSCs) from UCB presents technical challenges. Although MSCs have been isolated from UCB of diverse species such as human, equine, sheep, goat, and canine, there are inherent limitations of using UCB from these species for the expansion of MSCs. In this review, we investigated canine UCB (cUCB) and compared it with UCB from other species by reviewing recent articles published from February 2003 to June 2017 to gain an understanding of the limitations of cUCB in the acquisition of MSCs and to determine other suitable sources for the isolation of MSCs from canine. Our review indicates that cUCB is not an ideal source of MSCs because of insufficient volume and ethical issues. However, canine reproductive organs discarded during neutering may help broaden our understanding of effective isolation of MSCs. We recommend exploring canine reproductive and adipose tissue rather than UCB to fulfill the current need in veterinary medicine for the well-designed and ethically approved source of MSCs.

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BIOTECNOLOGIA DE CÉLULAS TRONCO MESENQUIMAIS: PRINCIPAIS APLICAÇÕES EM MEDICINA VETERINÁRIA E PERSPECTIVAS GERAIS

Colloquium Agrariae ◽

10.5747/ca.2017.v13.nesp2.000212 ◽

2017 ◽

Vol 13 (Especial 2) ◽

pp. 83-89

Author(s):

Elaine Cristina Galhardo ◽

Ariane Dantas ◽

Aline Sousa Camargos ◽

Fernanda da Cruz Landim

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Veterinary Medicine ◽

In Vitro Culture ◽

Adult Tissues ◽

Inflammatory Processes ◽

Specific Tissue

Mesenchymal Stem Cells (MSCs) are isolated from adult tissues and presents ability to originate identical cells or differentiate into specific tissue cells. Studies about in vitro culture and in vivo application of MSCs have pointed the potential to be explored in regenerative treatments and modulation of inflammatory processes, as well as the improvement of tissue engineering techniques and the development of biomaterials. Veterinary Medicine has presented, in several species, satisfactory results coming from the regenerative potential and paracrine activity characteristic of the MSCs. This review aimed, briefly showing promising results of the experimental MSCs application in Veterinary Medicine, its current biotechnological overview and general prospects.

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The Role of Mesenchymal Stem Cells (MSCs) in Veterinary Medicine and Their Use in Musculoskeletal Disorders

Biomolecules ◽

10.3390/biom11081141 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1141

Author(s):

Przemysław Prządka ◽

Krzysztof Buczak ◽

Ewelina Frejlich ◽

Ludwika Gąsior ◽

Kamil Suliga ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Veterinary Medicine ◽

Musculoskeletal Disorders ◽

Treatment Process ◽

Disease States ◽

Realistic Option ◽

Near Future ◽

Human And Animal Diseases

Regenerative medicine is a dynamically developing field of human and veterinary medicine. The animal model was most commonly used for mesenchymal stem cells (MSCs) treatment in experimental and preclinical studies with a satisfactory therapeutic effect. Year by year, the need for alternative treatments in veterinary medicine is increasing, and other applications for promising MSCs and their biological derivatives are constantly being sought. There is also an increase in demand for other methods of treating disease states, of which the classical treatment methods did not bring the desired results. Cell therapy can be a realistic option for treating human and animal diseases in the near future and therefore additional research is needed to optimize cell origins, numbers, or application methods in order to standardize the treatment process and assess its effects. The aim of the following work was to summarize available knowledge about stem cells in veterinary medicine and their possible application in the treatment of chosen musculoskeletal disorders in dogs and horses.

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Therapeutic mechanisms of mesenchymal stem cells in acute respiratory distress syndrome reveal potentials for Covid-19 treatment

Journal of Translational Medicine ◽

10.1186/s12967-021-02862-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Wendi Wang ◽

Wei Lei ◽

Lina Jiang ◽

Siqi Gao ◽

Shijun Hu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Animal Experiments ◽

Inflammatory Cells ◽

Beneficial Effects ◽

Therapeutic Mechanisms

AbstractThe mortality rate of critically ill patients with acute respiratory distress syndrome (ARDS) is 30.9% to 46.1%. The emergence of the coronavirus disease 2019 (Covid-19) has become a global issue with raising dire concerns. Patients with severe Covid-19 may progress toward ARDS. Mesenchymal stem cells (MSCs) can be derived from bone marrow, umbilical cord, adipose tissue and so on. The easy accessibility and low immunogenicity enable MSCs for allogeneic administration, and thus they were widely used in animal and clinical studies. Accumulating evidence suggests that mesenchymal stem cell infusion can ameliorate ARDS. However, the underlying mechanisms of MSCs need to be discussed. Recent studies showed MSCs can modulate immune/inflammatory cells, attenuate endoplasmic reticulum stress, and inhibit pulmonary fibrosis. The paracrine cytokines and exosomes may account for these beneficial effects. In this review, we summarize the therapeutic mechanisms of MSCs in ARDS, analyzed the most recent animal experiments and Covid-19 clinical trial results, discussed the adverse effects and prospects in the recent studies, and highlight the potential roles of MSC therapy for Covid-19 patients with ARDS.

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Conditioned medium derived from bovine umbilical mesenchymal stem cells as an alternative source of cell-free therapy

Veterinary World ◽

10.14202/vetworld.2021.2588-2595 ◽

2021 ◽

pp. 2588-2595

Author(s):

Dwi Liliek Kusindarta ◽

Hevi Wihadmadyatami

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Veterinary Medicine ◽

Umbilical Cord ◽

Ethical Issues ◽

Domestic Animals ◽

Hematopoietic Stem ◽

Efficient Treatment ◽

Major Interest ◽

Umbilical Cords

Umbilical cord blood (UCB) cells are an important source of mesenchymal stem cells (MSCs). It is known that the umbilical cord is rich in hematopoietic stem cells, which influenced research on ontogeny and transplantation (allogeneic transplantation). In recent years, stem cell research has emerged as an area of major interest due to its prospective applications in various aspects of both human and veterinary medicine. Moreover, it is known that the application of MSCs has several weaknesses. The use of these cells has limitations in terms of tumorigenesis effect, delivery, safety, and variability of therapeutic response, which led to the use of secretomes as an alternative to cell-free therapy. The main obstacle in its use is the availability of human UCB as an origin of MSCs and MSCs' secretomes, which are often difficult to obtain. Ethical issues regarding the use of stem cells based on human origin are another challenge, so an alternative is needed. Several studies have demonstrated that MSCs obtained from bovine umbilical cords have the same properties and express the same surface markers as MSCs obtained from human umbilical cords. Therefore, secretomes from MSCs derived from domestic animals (bovine) can possibly be used in human and veterinary medicine. This finding would contribute significantly to improve cell-free therapy. At present, the use of UCB MSCs derived from domestic animals, especially bovines, is very restricted, and only limited data about bovine UCB are available. Therefore, the aim of this review was to provide an updated overview of cell-free therapy and discuss the new possibilities introduced by the generation of this therapy derived from bovine umbilical MSCs as a promising tool in developing modern and efficient treatment strategies.

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Human Mesenchymal Stem Cells: The Present Alternative for High-Incidence Diseases, Even SARS-Cov-2

Stem Cells International ◽

10.1155/2020/8892189 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Karen J. Juárez-Navarro ◽

Eduardo Padilla-Camberos ◽

Néstor Fabián Díaz ◽

Ariel Miranda-Altamirano ◽

N. Emmanuel Díaz-Martínez

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Metabolic Diseases ◽

Human Mesenchymal Stem Cells ◽

Hiv Infections ◽

High Incidence ◽

Trial Protocols ◽

Therapeutic Molecules ◽

Therapeutic Mechanisms

Mesenchymal stem cells (MSCs), defined as plastic adherent cells with multipotent differentiation capacity in vitro, are an emerging and valuable tool to treat a plethora of diseases due to their therapeutic mechanisms such as their paracrine activity, mitochondrial and organelle transfer, and transfer of therapeutic molecules via exosomes. Nowadays, there are more than a thousand registered clinical trials related to MSC application around the world, highlighting MSC role on difficult-to-treat high-incidence diseases such as the current COVID-19, HIV infections, and autoimmune and metabolic diseases. Here, we summarize a general overview of MSCs and their therapeutic mechanisms; also, we discuss some of the novel clinical trial protocols and their results as well as a comparison between the number of registries, countries, and search portals.

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Mesenchymal Stem Cells in Premature Ovarian Insufficiency: Mechanisms and Prospects

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.718192 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhongkang Li ◽

Mingle Zhang ◽

Yanpeng Tian ◽

Qian Li ◽

Xianghua Huang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Therapeutic Potential ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Endocrine Disease ◽

Paracrine Effects ◽

Ovarian Cells ◽

Therapeutic Mechanisms ◽

Significant Attention

Premature ovarian insufficiency (POI) is a complex endocrine disease that severely affects the physiological and reproductive functions of females. The current conventional clinical treatment methods for POI are characterized by several side effects, and most do not effectively restore the physiological functions of the ovaries. Transplantation of mesenchymal stem cells (MSCs) is a promising regenerative medicine approach, which has received significant attention in the management of POI with high efficacy. Associated pre-clinical and clinical trials are also proceeding orderly. However, the therapeutic mechanisms underlying the MSCs-based treatment are complex and have not been fully elucidated. In brief, proliferation, apoptosis, immunization, autophagy, oxidative stress, and fibrosis of ovarian cells are modulated through paracrine effects after migration of MSCs to the injured ovary. This review summarizes therapeutic mechanisms of MSCs-based treatments in POI and explores their therapeutic potential in clinical practice. Therefore, this review will provide a theoretical basis for further research and clinical application of MSCs in POI.

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Role of Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Cardiac Tissue and Improvement of Cardiac Function: a Narrative Review

Biointerface Research in Applied Chemistry ◽

10.33263/briac111.84468456 ◽

2020 ◽

Vol 11 (1) ◽

pp. 8446-8456

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cardiac Function ◽

Cardiac Fibrosis ◽

Cardiac Tissue ◽

Trichostatin A ◽

Heart Tissue ◽

Left Ventricular ◽

Point Of View

Recent efforts have made in order to novel therapeutic approaches to reduce the heavy cardiovascular burden. The use of cell therapy and applying stem cell-based therapies has received much attention; of particular interest are adipose-derived mesenchymal stem cells (ADSCs). The present review aimed to review the studies which examined and researched various aspects of ADSCs to improve cardiac function. A comprehensive review of all articles assessed and discussed the application of ADSCs in the improvement of cardiac tissue renewing and cardiomyocytes regeneration was planned and conducted by the two reviewers. The initial literature search revealed a total of 153 articles that, of those, 34 were considered eligible. From the perspective of heart tissue regeneration, the inductive role of ADSCs in sensing mechanical stimulation and produce collagen and elastin scaffolds, vascularizing cardiac tissue, and exosomes (vesicles derived from ADSCs) in ADSCs‐mediated myocardial protection has indicated. In the process of ADSCs differentiation to cardiomyocyte- like cells, the role of various targeted pathways have been identified that can be influenced by different elements such as TGF-beta1, phorbol myristate acetate, Angiotensin II, Rho-associated kinases, 5-Azaytidine, Sodium valproate, fibrin scaffold and trichostatin A have been highlighted. In the final, from a therapeutic point of view, the effectiveness of ADMSCs differentiation to cardiomyocytes as improving left ventricular functional state has been discussed. Summarizing the studies confirms a significant improvement in cardiac function following direct application of ADSCs or their transformation to cardiomyocytes by stimulating or inhibiting various cellular pathways leading reducing oxidative stress and inflammatory bed, reducing cardiomyocyte apoptosis, attenuating cardiac fibrosis, reducing the infiltration of immune cells and collagen deposition, and enhancing angiogenesis.

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Mesenchymal stem cells in veterinary medicine

The Veterinary Nurse ◽

10.12968/vetn.2011.2.2.58 ◽

2011 ◽

Vol 2 (2) ◽

pp. 58-62

Author(s):

Rebecca Webster ◽

Ben Herbert ◽

Sinead Blaber ◽

Graham Vesey

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Veterinary Medicine

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