Usage of Human Mesenchymal Stem Cells in Cell-based Therapy:
                    Advantages and Disadvantages

Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable in vitro with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.

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SRT1720 promotes survival of aged human mesenchymal stem cells via FAIM: a pharmacological strategy to improve stem cell-based therapy for rat myocardial infarction

Cell Death and Disease ◽

10.1038/cddis.2017.107 ◽

2017 ◽

Vol 8 (4) ◽

pp. e2731-e2731 ◽

Cited By ~ 17

Author(s):

Xianbao Liu ◽

Dexing Hu ◽

Zhiru Zeng ◽

Wei Zhu ◽

Na Zhang ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Human Mesenchymal Stem Cells ◽

Cell Based Therapy

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Cell-based therapy in ovarian cancer: Improved adenoviral transduction strategy of human mesenchymal stem cells as tumor-homing drug factories

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.01.150 ◽

2015 ◽

Vol 137 ◽

pp. 64

Author(s):

L.M. Kuroki ◽

I. Dmitriev ◽

J. Gibbs ◽

K. Tatzel ◽

M.A. Powell ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Cell Based Therapy ◽

Adenoviral Transduction ◽

Tumor Homing

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Senescence in Human Mesenchymal Stem Cells: Functional Changes and Implications in Stem Cell-Based Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms17071164 ◽

2016 ◽

Vol 17 (7) ◽

pp. 1164 ◽

Cited By ~ 175

Author(s):

Valentina Turinetto ◽

Emanuela Vitale ◽

Claudia Giachino

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Human Mesenchymal Stem Cells ◽

Functional Changes ◽

Cell Based Therapy

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Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00180.2011 ◽

2012 ◽

Vol 302 (10) ◽

pp. L1003-L1013 ◽

Cited By ~ 190

Author(s):

Anna Krasnodembskaya ◽

Gianluca Samarani ◽

Yuanlin Song ◽

Hanjing Zhuo ◽

Xiao Su ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Phagocytic Activity ◽

Human Mesenchymal Stem Cells ◽

Blood Monocytes ◽

Bacterial Colony ◽

Gram Negative ◽

Beneficial Effects ◽

Cell Based Therapy ◽

Inflammatory Protein

The potential therapeutic value of cell-based therapy with mesenchymal stem cells (MSC) has been reported in mouse models of polymicrobial peritoneal sepsis. However, the mechanisms responsible for the beneficial effects of MSC have not been well defined. Therefore, we tested the therapeutic effect of intravenous bone marrow-derived human MSC in peritoneal sepsis induced by gram-negative bacteria. At 48 h, survival was significantly increased in mice treated with intravenous MSC compared with control mice treated with intravenous fibroblasts (3T3) or intravenous PBS. There were no significant differences in the levels of TNF-α, macrophage inflammatory protein 2, or IL-10 in the plasma. However, there was a marked reduction in the number of bacterial colony-forming units of Pseudomonas aeruginosa in the blood of MSC-treated mice compared with the 3T3 and PBS control groups. In addition, phagocytic activity was increased in blood monocytes isolated from mice treated with MSC compared with the 3T3 and PBS groups. Furthermore, levels of C5a anaphylotoxin were elevated in the blood of mice treated with MSC, a finding that was associated with upregulation of the phagocytosis receptor CD11b on monocytes. The phagocytic activity of neutrophils was not different among the groups. There was also an increase in alternately activated monocytes/macrophages (CD163- and CD206-positive) in the spleen of the MSC-treated mice compared with the two controls. Thus intravenous MSC increased survival from gram-negative peritoneal sepsis, in part by a monocyte-dependent increase in bacterial phagocytosis.

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Dexamethasone Priming Enhances Stemness and Immunomodulatory Property of Tissue-specific Human Mesenchymal Stem Cells

10.21203/rs.3.rs-446758/v1 ◽

2021 ◽

Author(s):

Sonali Rawat ◽

Vatsla Dadhwal ◽

Sujata Mohanty

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Prostaglandin E ◽

Dependent Manner ◽

Tissue Specific ◽

Immunomodulatory Property ◽

Cell Based Therapy ◽

Anti Inflammatory ◽

Basic Characteristics

Abstract Background: Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone (Dex) is a powerful anti-inflammatory compound that is widely used as therapy in autoimmune disease conditions or allogeneic transplantation. However, minimal immunomodulatory effect of hMSCs may limit their therapeutic uses. Moreover, the effect of glucocorticoids on the immunomodulatory molecules or other regenerative properties of tissue-specific hMSCs remains unknown. Method: Herein, we evaluated the in vitro effect of Dex at various dose concentrations and time intervals, 1000 ng/ml, 2000 ng/ml, 3000 ng/ml and 24 h, 48 h respectively, on the basic characteristics and immunomodulatory properties of Bone marrow derived MSC (BM-MSCs), Adipose tissue derived MSCs (AD-MSCs), Dental Pulp derived MSC (DP-MSCs) and Umbilical cord derived MSCs (UC-MSCs). Results: The present study indicated that the concentration of Dex did not ramify the cellular morphology nor showed cytotoxicity as well as conserved the basic characteristics of tissue specific hMSCs including cell proliferation and surface marker profiling. However, quite interestingly it was observed that the stemness markers (Oct-4, Sox-2, Nanog & Klf-4) showed a significant upregulation in DP-MSCs and AD-MSCs followed by UC-MSCs and BM-MSCs. Additionally, immunomodulatory molecules, Prostaglandin E-2 (PGE-2), Indoleamine- 2,3-dioxygenase (IDO) and Human Leukocyte Antigen-G (HLA-G) were seen to be upregulated in a dose-dependent manner. Moreover, there was a differential response of tissue specific hMSCs after pre-conditioning with Dex during mixed lymphocyte reaction, wherein UC-MSCs and DP-MSCs showed enhanced immunosuppression as compared to AD-MSCs and BM-MSCs, thereby proving to be a better candidate for therapeutic applications in immune-related diseases. Conclusion: Dex preconditioning ameliorates the hMSCs immunomodulatory property and may void the challenge associated with minimal potency and strengthen their therapeutic efficacy.

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