• IMMUNE NETWORK
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• 제14권2호
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• pp.81-88
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• 2014

Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-${\beta}$, hepatic growth factors, prostaglandin $E_2$, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.

• Medical Lasers
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• 제9권2호
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• pp.119-125
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• 2020

Photobiomodulation forms the basis of photomedicine and is defined as the effect of coherent or non-coherent light sources, such as low-level lasers and light-emitting diodes, on cells and tissues. This treatment technique affects cell functions, proliferation, and migration, and plays an important role in tissue regeneration. Mesenchymal stem cells (MSCs) are known to be beneficial for tissue regeneration, and the combination of stem cell therapy and laser therapy appears to positively affect treatment outcomes. In general, a low-power laser has a positive effect on MSCs, thereby facilitating improvements in different disease models. This study elucidates the mechanisms and effects of low-power laser irradiation on the proliferation, migration, and differentiation of various MSCs that have been examined in different studies.

• Journal of Applied Biological Chemistry
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• 제50권4호
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• pp.187-195
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• 2007

The cord blood serves as a vehicle for the transportation of oxygen and nutrients to the fetus. In the past, the human cord blood has generally been discarded after birth. However, numerous studies have described the regenerative ability of the cord blood cells in various incurable diseases. The umbilical cord blood (UCB)-derived stem cells are obtained through non-invasive methods that are not harmful to both the mother and the fetus. Furthermore, the cord blood stem cells are more immature than the adult stem cells and expand readily in vitro. The mesenchymal stem cells (MSCs) have the capacity to differentiate in vitro into various mesodermal (bone, cartilage, tendon, muscle, and adipose), endodermal (hepatocyte), and ectodermal (neurons) tissues. This review describes the immunological properties of the human UCB-MSCs to assess their potential usefulness in the allogeneic transplantation for the regenerative medicine.

• 한국동물생명공학회지
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• 제37권4호
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• pp.246-254
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• 2022

Current studies have revealed the capacity of mesenchymal stem cells (MSCs) in term of immunomodulatory properties, and this distinct potential is downgraded according to the disease duration of patients-derived MSCs. In order to enhance the immunomodulatory and anti-tumorigenic properties of the rheumatoid arthritis (RA) joints-derived MSCs, we aggregate synovial fluid-derived MSCs from RA joints (RA-hMSCs) into 3D-spheroids by the use of hanging drop culture method. Cells were isolated from synovial fluids of RA joints with longstanding active status over 13 years. For aggregation of RA-hMSCs into 3D-spheroids, cells were plated in hanging drops in 30 μL of advanced DMEM (ADMEM) containing 25,000-30,000 cells/drop and cultured for 48 h. To analyze the comparative immunomodulatory effects of 3D-spheroid and 2D monolayer cultured RA-hMSCs and then cells were cultured in ADMEM supplemented with 20% of synovial fluids of RA patients for 48 h and were evaluated by qRT-PCR for their expression of mRNA levels of inflammatory and anti-inflammatory markers. Cellular aggregation of RA-hMSCs was observed and cells were aggregate into a single sphere. Following treatment of RA patient's synovial fluids into the RA-hMSCs, spheroids formed RA-hMSCs showed significantly (p < 0.05) higher expression of TNFα stimulated gene/protein 6 (TSG-6) than the monolayer cultured RA-hMSCs. Therefore, the 3D-spheroid culture methods of RA-hMSCs were more effective than 2D monolayer cultures in suppressing inflammatory response treated with 20% of RA-synovial fluids by expression of TNFα (TSG-6) according to the immune response and enhanced secretion of inflammatory factors.

• 한국임상수의학회지
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• 제40권5호
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• pp.323-329
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• 2023

Peripheral blood-derived mesenchymal stem cells (PB-MSCs) have shown promise in cell-based therapy, as they can be harvested with ease through minimally invasive procedures. This study aimed to isolate PB-MSCs from foals and mares and to compare the proliferation and cellular characteristics of the PB-MSCs between the two groups. Six pairs of mares and their foals were used in this study. MSCs were isolated from PB by direct plating in a tissue culture medium, and cell proliferation (population doubling time [PDT], and colony-forming unit-fibroblast assay [CFU-F]), and characterization (morphology, plastic adhesiveness, colony formation, trilineage differentiation) were examined. There was no significant difference in the PB-MSC yield, CFU-F, and PDT between the mares and foals. PB-MSCs from both mares and foals showed typical MSC characteristics in terms of spindle-shaped morphology, plastic adhesive properties, formation of colonies, trilineage differentiation. These results suggest that PB-MSCs isolated from horses, both adult horses, and foals, can be used for equine cell-based therapy.

• BMB Reports
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• 제53권2호
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• pp.65-73
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• 2020

Life expectancy has dramatically increased around the world over the last few decades, and staying healthier longer, without chronic disease, has become an important issue. Although understanding aging is a grand challenge, our understanding of the mechanisms underlying the degeneration of cell and tissue functions with age and its contribution to chronic disease has greatly advanced during the past decade. As our immune system alters with aging, abnormal activation of immune cells leads to imbalance of innate and adaptive immunity and develops a persistent and mild systemic inflammation, inflammaging. With their unique therapeutic properties, such as immunomodulation and tissue regeneration, mesenchymal stem cells (MSCs) have been considered to be a promising source for treating autoimmune disease or as anti-aging therapy. Although direct evidence of the role of MSCs in inflammaging has not been thoroughly studied, features reported in senescent MSCs or the aging process of MSCs are associated with inflammaging; MSC niche-driven skewing of hematopoiesis toward the myeloid lineage or oncogenesis, production of pro-inflammatory cytokines, and weakening their modulative property on macrophage polarization, which plays a central role on inflammaging development. This review explores the role of senescent MSCs as an important regulator for onset and progression of inflammaging and as an effective target for anti-aging strategies.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.16-23
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• 2010

Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte differentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, $PPAR{\gamma}$ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) agonist, significantly reduced the levels of anti-adipogenic $PGE_2$ in IDX-conditioned hBM-MSC culture supernatants when compared to $PGE_2$ levels in the absence of $PPAR{\gamma}$ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease $PGE_2$ levels in culture. These results suggest that the role of $PPAR{\gamma}$ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic $PGE_2$ levels through the up-regulation of HPGD expression.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제47권2호
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• pp.65-75
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• 2021

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.

• BMB Reports
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• 제57권5호
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• pp.238-243
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• 2024

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BM-MSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment.

• Biomolecules & Therapeutics
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• 제21권6호
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• pp.447-453
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• 2013

Chondroitin sulfate proteoglycan (CSPG) inhibits neurite outgrowth of various neuronal cell types, and CSPG-associated inhibition of neurite outgrowth is mediated by the Rho/ROCK pathway. Mesenchymal stromal/stem cells (MSCs) have the potential to differentiate into neuron-like cells under specific conditions and have been shown to differentiate into neuron-like cells by co-treatment with the ROCK inhibitor Y27632 and the hypoxia condition mimicking agent $CoCl_2$. In this study, we addressed the hypothesis that a ROCK inhibitor might be beneficial to regenerate neurons during stem cell therapy by preventing transplanted MSCs from inhibition by CSPG in damaged tissues. Indeed, dose-dependent inhibition by CSPG pretreatment was observed during morphological changes of Wharton's jelly-derived MSCs (WJ-MSCs) induced by Y27632 alone. The formation of neurite-like structures was significantly inhibited when WJ-MSCs were pre-treated with CSPG before induction under Y27632 plus $CoCl_2$ conditions, and pretreatment with a protein kinase C inhibitor reversed such inhibition. However, CSPG treatment resulted in no significant inhibition of the WJ-MSC morphological changes into neuron-like cells after initiating induction by Y27632 plus $CoCl_2$. No marked changes were detected in expression levels of neuronal markers induced by Y27632 plus $CoCl_2$ upon CSPG treatment. CSPG also blocked the morphological changes of human bone marrow-derived MSCs into neuron-like cells under other neuronal induction condition without the ROCK inhibitor, and Y27632 pre-treatment blocked the inhibitory effect of CSPG. These results suggest that a ROCK inhibitor can be efficiently used in stem cell therapy for neuronal induction by avoiding hindrance from CSPG.