Acute Skin Wounds Treated with Mesenchymal Stem Cells and Biopolymer Compositions Alone and in Combination: Evaluation of Agent Efficacy and Analysis of Healing Mechanisms

We studied the efficacy of using mesenchymal stem cells (MSC) and a polymeric compound (based on chitosan and cellulose with integrated cerium dioxide nanoparticles (PCCD)) in wound healing, and to compare the effects with various invasive and external drugs used for the same purpose. Two wounds were made on the backs of each of 112 Wistar rats, removing the skin. Eight groups were studied: Control_0—intact wounds; Control_ss—0.9% NaCl injections; MSC injections; Control_msc—intact wounds on the opposite side of the body from the MSC group; external application of the PCCD; external application of a combination of the drugs PCCD + MSC; DCh –ointment Dioxomethyltetrahydropyrimidine + Chloramphenicol; and DHCB—injections of a deproteinized hemoderivative of calf blood. After 14 days, we evaluated the state and size of the wounds, studied the level of microcirculation, performed a histological study, and identified and counted the different types of cells. The most effective remedy was combination PCCD + MSC. The treatments in the PCCD and MSC groups were more effective than in the DHCB and DCh groups. Invasive drugs and DCh slowed the regeneration process. DHCB did not affect the rate of healing for acute wounds without ischemia during the first week. The proven efficacy of developed polymeric compounds demonstrates the feasibility of further studies in clinical practice.

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In vivo Evaluation of a Collagen Scaffold Preconditioned with Adipose-derived Mesenchymal Stem Cells Used for Bone Regeneration A histological study

Materiale Plastice ◽

10.37358/mp.18.4.5102 ◽

2018 ◽

Vol 55 (4) ◽

pp. 691-695

Author(s):

Tudor Sorin Pop ◽

Anca Maria Pop ◽

Alina Dia Trambitas Miron ◽

Klara Brinzaniuc ◽

Simona Gurzu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Histological Study ◽

Collagen Scaffold ◽

Bone Defects ◽

Collagen Scaffolds ◽

In Vivo Evaluation ◽

Calvarial Bone ◽

Bone Apposition

The use of collagen scaffolds and stem cells for obtaining a tissue-engineering complex has been an important concept in promoting repair and regeneration of the bone tissue. Such units represent important steps in the development of an ideal scaffold-cell complex that would sustain new bone apposition. The aim of our study was to perform a histologic evaluation of the healing of critical-sized bone defects, using a biologic collagen scaffold with adipose-derived mesenchymal stem cells, in comparison to negative controls created in the adjacent bone. We used 16 Wistar rats and according to the study design 2 calvarial bone defects were created in each animal, one was filled with collagen seeded with adipose-derived stem cells and the other one was considered negative control. During the following month, at weekly intervals, the animals were euthanized and the specimens from bone defects were histologically evaluated. The results showed that these scaffolds were highly biocompatible as only moderate inflammation no rejection reactions were observed. Furthermore, the first signs of osseous healing appeared after two weeks accompanied by angiogenesis. Collagen scaffolds seeded with adipose-derived mesenchymal stem cells can be considered a promising treatment option in bone regeneration of large defects.

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Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽

10.3390/biomedicines9060667 ◽

2021 ◽

Vol 9 (6) ◽

pp. 667

Author(s):

Gabriella Racchetti ◽

Jacopo Meldolesi

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Responses ◽

Extracellular Vesicles ◽

Immune Regulation ◽

Great Increase ◽

The Body ◽

Cell Aging ◽

Therapeutic Effects ◽

Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

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Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application

npj Regenerative Medicine ◽

10.1038/s41536-021-00122-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Kangkang Zha ◽

Xu Li ◽

Zhen Yang ◽

Guangzhao Tian ◽

Zhiqiang Sun ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Cartilage Repair ◽

Cartilage Damage ◽

Cartilage Regeneration ◽

Great Promise ◽

Traditional Treatment ◽

Different Types ◽

Selection Of

AbstractArticular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.

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Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

Current Drug Targets ◽

10.2174/1389450122666210824142247 ◽

2021 ◽

Vol 22 ◽

Author(s):

Soheila Montazersaheb ◽

Ezzatollah Fathi ◽

Ayoub Mamandi ◽

Raheleh Farahzadi ◽

Hamid Reza Heidari

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tumor Microenvironment ◽

Cancer Stem Cells ◽

Tumor Cells ◽

Cell Types ◽

Cell Interaction ◽

Therapeutic Interventions ◽

Tumorigenic Potential ◽

Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

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A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

International Journal of Molecular Sciences ◽

10.3390/ijms19123968 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3968 ◽

Cited By ~ 17

Author(s):

Enrico Spugnini ◽

Mariantonia Logozzi ◽

Rossella Di Raimo ◽

Davide Mizzoni ◽

Stefano Fais

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

The Body ◽

Mesenchymal Transition ◽

Metastatic Cascade ◽

Target Organs

Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial–mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches” in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors.

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The Latest Developments in Immunomodulation of Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions, Both Allogeneic and Autologous

Frontiers in Immunology ◽

10.3389/fimmu.2021.785717 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jia-ming Chen ◽

Qiao-yi Huang ◽

Yun-xia Zhao ◽

Wei-hong Chen ◽

Shu Lin ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mhc Class I ◽

Mhc Class Ii ◽

The Body ◽

Immune Rejection ◽

Intrauterine Adhesions ◽

Allogeneic Mscs ◽

Intrauterine Adhesion ◽

Low Levels

Intrauterine adhesion (IUA) is an endometrial fibrosis disease caused by repeated operations of the uterus and is a common cause of female infertility. In recent years, treatment using mesenchymal stem cells (MSCs) has been proposed by many researchers and is now widely used in clinics because of the low immunogenicity of MSCs. It is believed that allogeneic MSCs can be used to treat IUA because MSCs express only low levels of MHC class I molecules and no MHC class II or co-stimulatory molecules. However, many scholars still believe that the use of allogeneic MSCs to treat IUA may lead to immune rejection. Compared with allogeneic MSCs, autologous MSCs are safer, more ethical, and can better adapt to the body. Here, we review recently published articles on the immunomodulation of allogeneic and autologous MSCs in IUA therapy, with the aim of proving that the use of autologous MSCs can reduce the possibility of immune rejection in the treatment of IUAs.

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Mesenchymal Stem Cell Derived-Exosomes as Effective Factors in Reducing Cytokine Storm Symptoms of COVID-19

Protein and Peptide Letters ◽

10.2174/0929866528666210222150347 ◽

2021 ◽

Vol 28 ◽

Author(s):

Amir Hossein Kheirkhah ◽

Seyed Hossein Shahcheraghi ◽

Malihe lotfi ◽

Marzieh lotfi ◽

Sanaz Raeisi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune System ◽

Host Immune System ◽

Cytokine Storm ◽

Infection Transmission ◽

Effective Factors ◽

Different Types ◽

Immune System Modulation

: Given that conventional therapies are ineffective for COVID-19, obtained exosomes from stem cells have been proposed as a sustainable and effective treatment. Exosomes are subsets with lengths between 30 and 100 nanometers, and they can be secreted by different cells. Exosomes are containing different types of miRNAs, mRNAs, and different proteins. The role of immune system modulation of exosomes of mesenchymal stem cells has been studied and confirmed in more than one study. Exosome miRNAs detect and reduce cytokines that cause cytokine storms such as IL-7, IL-2, IL-6, etc. These miRNAs include miR-21, miR-24, miR-124, miR-145, etc. The risks associated with treatment with exosomes from different cells are relatively small compared to other treatments because transplanted cells do not stimulate the host immune system and also has reduced infection transmission. Due to the ineffectiveness of existing drugs in reducing inflammation and preventing cytokine storms, the use of immune-boosting systems may be suggested as another way to control cytokine storm.

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The Role of Tumor-Associated Macrophages in Leukemia

Acta Haematologica ◽

10.1159/000500315 ◽

2019 ◽

Vol 143 (2) ◽

pp. 112-117 ◽

Cited By ~ 2

Author(s):

Yueyang Li ◽

M. James You ◽

Yaling Yang ◽

Dongzhi Hu ◽

Chen Tian

Keyword(s):

Stem Cells ◽

Innate Immunity ◽

Mesenchymal Stem Cells ◽

Immune Cells ◽

Leukemia Cell ◽

Tumor Associated Macrophages ◽

Intrinsic Factors ◽

Different Types ◽

Tumor Growth And Metastasis

In addition to intrinsic factors, leukemia cell growth is influenced by the surrounding nonhematopoietic cells in the leukemic microenvironment, including fibroblasts, mesenchymal stem cells, vascular cells, and various immune cells. Despite the fact that macrophages are an important component of human innate immunity, tumor-associated macrophages (TAMs) have long been considered as an accomplice promoting tumor growth and metastasis. TAMs are activated by an abnormal malignant microenvironment, polarizing into a specific phenotype and participating in tumor progression. TAMs that exist in the microenvironment of different types of leukemia are called leukemia-associated macrophages (LAMs), which are reported to be associated with the progression of leukemia. This review describes the role of LAMs in different leukemia subtypes.

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Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.2018.18.03.002 ◽

2018 ◽

Vol 18 (3) ◽

pp. 264 ◽

Cited By ~ 52

Author(s):

Roberto Berebichez-Fridman ◽

Pablo R. Montero-Olvera

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Regenerative Medicine ◽

Adult Stem Cells ◽

Current Knowledge ◽

Clinical Applications ◽

The Body ◽

Differentiation Potential ◽

Advantages And Disadvantages

First discovered by Friedenstein in 1976, mesenchymal stem cells (MSCs) are adult stem cells found throughout the body that share a fixed set of characteristics. Discovered initially in the bone marrow, this cell source is considered the gold standard for clinical research, although various other sources—including adipose tissue, dental pulp, mobilised peripheral blood and birth-derived tissues—have since been identified. Although similar, MSCs derived from different sources possess distinct characteristics, advantages and disadvantages, including their differentiation potential and proliferation capacity, which influence their applicability. Hence, they may be used for specific clinical applications in the fields of regenerative medicine and tissue engineering. This review article summarises current knowledge regarding the various sources, characteristics and therapeutic applications of MSCs.Keywords: Mesenchymal Stem Cells; Adult Stem Cells; Regenerative Medicine; Cell Differentiation; Tissue Engineering.

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Control of Differentiation of Human Mesenchymal Stem Cells by Altering the Geometry of Nanofibers

Journal of Nanotechnology ◽

10.1155/2012/429890 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Satoshi Fujita ◽

Harue Shimizu ◽

Shin-ichiro Suye

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Clinical Applications ◽

Soluble Factors ◽

Precise Control ◽

Mixed Medium ◽

Aligned Nanofibers ◽

Different Types ◽

Msc Differentiation

Effective differentiation of mesenchymal stem cells (MSCs) is required for clinical applications. To control MSC differentiation, induction media containing different types of soluble factors have been used to date; however, it remains challenging to obtain a uniformly differentiated population of an appropriate quality for clinical application by this approach. We attempted to develop nanofiber scaffolds for effective MSC differentiation by mimicking anisotropy of the extracellular matrix structure, to assess whether differentiation of these cells can be controlled by using geometrically different scaffolds. We evaluated MSC differentiation on aligned and random nanofibers, fabricated by electrospinning. We found that induction of MSCs into adipocytes was markedly more inhibited on random nanofibers than on aligned nanofibers. In addition, adipoinduction on aligned nanofibers was also inhibited in the presence of mixed adipoinduction and osteoinduction medium, although osteoinduction was not affected by a change in scaffold geometry. Thus, we have achieved localized control over the direction of differentiation through changes in the alignment of the scaffold even in the presence of a mixed medium. These findings indicate that precise control of MSC differentiation can be attained by using scaffolds with different geometry, rather than by the conventional use of soluble factors in the medium.

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