scholarly journals Functional enhancement strategies for immunomodulation of mesenchymal stem cells and their therapeutic application

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Byung-Chul Lee ◽  
Kyung-Sun Kang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Genetic Manipulation ◽  
Culture Method ◽  
Research Field ◽  
Innate Immune ◽  
Patient Specific ◽  
Immune Disorders ◽  
Bioactive Substances ◽  
Promising Alternative

Abstract Mesenchymal stem cells (MSCs) have recently been considered a promising alternative treatment for diverse immune disorders due to their unique biomedical potentials including the immunomodulatory property and ability to promote tissue regeneration. However, despite many years of pre-clinical studies in the research field, results from clinical trials using these cells have been diverse and conflicting. This discrepancy is caused by several factors such as poor engraftment, low survival rate, and donor-dependent variation of the cells. Enhancement of consistency and efficacy of MSCs remains a challenge to overcome the current obstacles to MSC-based therapy and subsequently achieve an improved therapeutic outcome. In this review, we investigated function enhancement strategies by categorizing as preconditioning, genetic manipulation, usage of supportive materials, and co-administration with currently used drugs. Preconditioning prior to MSC application makes up a large proportion of improvement strategies and preconditioning reagents include bioactive substances (cytokines, growth factors, and innate immune receptor agonists), hypoxia, and modification in culture method. With the piled results from previous studies using each method, disease- or patient-specific therapy has become more important than ever. On the other hand, genetic manipulation targeting therapeutic-associated factors or co-administration of biocompatible materials has also arisen as other therapeutic strategies. Thus, we summarized several specialized tactics by analyzing up-to-date results in the field and proposed some promising enhancement methods to improve the clinical outcomes for MSC therapy.

scholarly journals Identifying the Therapeutic Significance of Mesenchymal Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1145 ◽  
Author(s):  
Vineet Kumar Mishra ◽  
Hui-Hsuan Shih ◽  
Farzana Parveen ◽  
David Lenzen ◽  
Etsuro Ito ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Metabolic Disorders ◽  
Cellular Therapy ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Immune Disorders ◽  
Therapeutic Role ◽  
Beneficial Effects ◽  
Immense Potential

The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in immune disorders. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and conceal themselves from the innate immune system. These signatures are the reason for the uprising in the sciences of cellular therapy in the last decades. Irrespective of their therapeutic role in immune disorders, some factors limit beneficial effects such as inconsistency of cell characteristics, erratic protocols, deviating dosages, and diverse transfusion patterns. Conclusive protocols for cell culture, differentiation, expansion, and cryopreservation of MSCs are of the utmost importance for a better understanding of MSCs in therapeutic applications. In this review, we address the immunomodulatory properties and immunosuppressive actions of MSCs. Also, we sum up the results of the enhancement, utilization, and therapeutic responses of MSCs in treating inflammatory diseases, metabolic disorders and diabetes.

Recent Advances in Endocrine, Metabolic and Immune Disorders: Mesenchymal Stem Cells (MSCs) and Engineered Scaffolds

2018 ◽  
Vol 18 (5) ◽  
pp. 466-469 ◽  
Author(s):  
Stefania Cantore ◽  
Vito Crincoli ◽  
Antonio Boccaccio ◽  
Antonio E. Uva ◽  
Michele Fiorentino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Disorders ◽  
Recent Advances

scholarly journals Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Xiaoyu Pu ◽  
Siyang Ma ◽  
Yan Gao ◽  
Tiankai Xu ◽  
Pengyu Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Radiation Damage ◽  
Therapeutic Potential ◽  
Damage Model ◽  
Bioactive Substances ◽  
Radiation Induced ◽  
Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

Construction of Tissue Engineered Skin with VEGF-Modified Human Mesenchymal Stem Cells and Acellular Dermal Matrix

2009 ◽  
Vol 610-613 ◽  
pp. 1298-1301
Author(s):  
Xiang Rong Zhang ◽  
De Wu Liu ◽  
Guang Hua Guo ◽  
Yan Peng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gradient Centrifugation ◽  
Human Mesenchymal Stem Cells ◽  
Acellular Dermal Matrix ◽  
Culture Method ◽  
Gene Encoding ◽  
Dermal Matrix ◽  
Acellular Dermal

The development of skin tissue engineering provides a noninvasive method for skin restoration. Unfortunately, the lack of a vascular plexus leads to greater time for vascularization compared with native skin autografts and contributes to graft failure. Our purpose was to construct tissue-engineered skin with VEGF- modified human bone marrow mesenchymal stem cells (hMSCs) as well as acellular dermal matrix(ADM) in vitro , Thus by increased vascular endothelial growth factor expression, which could prospectively improve vascularization of tissue-engineered skin for wound healing applications. To reach this aim, hMSCs were isolated and cultured with density gradient centrifugation combined with attachment culture method in vitro. Liposome- mediated gene transfer was used to generate a population of hMSCs overexpressing the gene encoding VEGF165. Then VEGF- modified hMSCs were seeded onto the surface of ADM. The experimental results showed that ADM we prepared has good compatibility with MSCs, the cells in ADM grew and proliferated well in vitro and the tissue - engineered skin with VEGF- modified hMSCs and ADM has been successfully constructed.

scholarly journals Comparison of Immunosuppressive and Angiogenic Properties of Human Amnion-Derived Mesenchymal Stem Cells between 2D and 3D Culture Systems

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Vitale Miceli ◽  
Mariangela Pampalone ◽  
Serena Vella ◽  
Anna Paola Carreca ◽  
Giandomenico Amico ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Three Dimensional ◽  
3D Culture ◽  
Culture Method ◽  
Paracrine Factors ◽  
Human Amnion ◽  
Tissue Repair And Regeneration ◽  
3D Culture System

The secretion of potential therapeutic factors by mesenchymal stem cells (MSCs) has aroused much interest given the benefits that it can bring in the field of regenerative medicine. Indeed, the in vitro multipotency of these cells and the secretive capacity of both angiogenic and immunomodulatory factors suggest a role in tissue repair and regeneration. However, during culture, MSCs rapidly lose the expression of key transcription factors associated with multipotency and self-renewal, as well as the ability to produce functional paracrine factors. In our study, we show that a three-dimensional (3D) culture method is effective to induce MSC spheroid formation, to maintain the multipotency and to improve the paracrine activity of a specific population of human amnion-derived MSCs (hAMSCs). The regenerative potential of both 3D culture-derived conditioned medium (3D CM) and their exosomes (EXO) was assessed against 2D culture products. In particular, tubulogenesis assays revealed increased capillary maturation in the presence of 3D CM compared with both 2D CM and 2D EXO. Furthermore, 3D CM had a greater effect on inhibition of PBMC proliferation than both 2D CM and 2D EXO. To support this data, hAMSC spheroids kept in our 3D culture system remained viable and multipotent and secreted considerable amounts of both angiogenic and immunosuppressive factors, which were detected at lower levels in 2D cultures. This work reveals the placenta as an important source of MSCs that can be used for eventual clinical applications as cell-free therapies.

scholarly journals Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Gopu Sriram ◽  
Vaishali Prakash Natu ◽  
Intekhab Islam ◽  
Xin Fu ◽  
Chaminda Jayampath Seneviratne ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Innate Immune Response ◽  
Embryonic Stem ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Multipotent Stem Cells ◽  
Cytokine Expression Profile ◽  
The Impact

Periodontitis involves complex interplay of bacteria and host immune response resulting in destruction of supporting tissues of the tooth. Toll-like receptors (TLRs) play a role in recognizing microbial pathogens and eliciting an innate immune response. Recently, the potential application of multipotent stem cells and pluripotent stem cells including human embryonic stem cells (hESCs) in periodontal regenerative therapy has been proposed. However, little is known about the impact of periodontopathogens on hESC-derived progenies. This study investigates the effects of heat-killed periodontopathogens, namely,Porphyromonas gingivalisandAggregatibacter actinomycetemcomitans, on TLR and cytokine expression profile of hESC-derived progenies, namely, fibroblasts (hESC-Fib) and mesenchymal stem cells (hESC-MSCs). Additionally, the serotype-dependent effect ofA. actinomycetemcomitanson hESC-derived progenies was explored. Both hESC-Fib and hESC-MSCs constitutively expressedTLR-2andTLR-4. hESC-Fib upon exposure to periodontopathogens displayed upregulation of TLRs and release of cytokines (IL-1β, IL-6, and IL-8). In contrast, hESC-MSCs were largely nonresponsive to bacterial challenge, especially in terms of cytokine production. Further, exposure of hESC-Fib toA. actinomycetemcomitansserotype c was associated with higher IL-8 production than serotype b. In contrast, the hESC-MSCs displayed no serotype-dependent response. Differential response of the two hESC progenies implies a phenotype-dependent response to periodontopathogens and supports the concept of immunomodulatory properties of MSCs.

scholarly journals Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Shuang Liu ◽  
Minae Takahashi ◽  
Takeshi Kiyoi ◽  
Kensuke Toyama ◽  
Masaki Mogi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Calcium Release ◽  
Therapeutic Potential ◽  
Genetic Manipulation ◽  
Adipogenic Differentiation ◽  
Genetically Engineered ◽  
Clinical Implementation ◽  
Human Cartilage ◽  
Crac Channel

Calcium is a ubiquitous intracellular messenger that has a crucial role in determining the proliferation, differentiation, and functions of multipotent mesenchymal stem cells (MSCs). Our study is aimed at elucidating the influence of genetically manipulating Ca2+ release-activated Ca2+ (CRAC) channel-mediated intercellular Ca2+ signaling on the multipotency of MSCs. The abilities of genetically engineered MSCs, including CRAC-overexpressing and CRAC-knockout MSCs, to differentiate into multiple mesenchymal lineages, including adipogenic, osteogenic, and chondrogenic lineages, were evaluated. CRAC channel-mediated Ca2+ influx into these cells was regulated, and the differentiation fate of MSCs was modified. Upregulation of intracellular Ca2+ signals attenuated the adipogenic differentiation ability and slightly increased the osteogenic differentiation potency of MSCs, whereas downregulation of CRACM1 expression promoted chondrogenic differentiation potency. The findings demonstrated the effects of genetically manipulating MSCs by targeting CRACM1. CRAC-modified MSCs had distinct differentiation fates to adipocytes, osteoblasts, and chondrocytes. To aid in the clinical implementation of tissue engineering strategies for joint regeneration, these data may allow us to identify prospective factors for effective treatments and could maximize the therapeutic potential of MSC-based transplantation.

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