• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.153-162
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• 2020

Spinal cord injury (SCI) is one of the most devastating conditions and many SCI patients suffer neurological sequelae. Stem cell therapies are expected to be beneficial for many patients with central nervous system injuries, including SCI. Adult stem cells (ASCs) are not associated with the risks which embryonic stem cells have such as malignant transformation, or ethical problems, and can be obtained relatively easily. Consequently, many researchers are currently studying the effects of ASCs in clinical trials. The environment of transplanted cells applied in the injured spinal cord differs between the phases of SCI; therefore, many researchers have investigated these phases to determine the optimal time window for stem cell therapy in animals. In addition, the results of clinical trials should be evaluated according to the phase in which stem cells are transplanted. In general, the subacute phase is considered to be optimal for stem cell transplantation. Among various candidates of transplantable ASCs, mesenchymal stem cells (MSCs) are most widely studied due to their clinical safety. MSCs are also less immunogenic than neural stem/progenitor cells and consequently immunosuppressants are rarely required. Attempts have been made to enhance the effects of stem cells using scaffolds, trophic factors, cytokines, and other drugs in animal and/or human clinical studies. Over the past decade, several clinical trials have suggested that transplantation of MSCs into the injured spinal cord elicits therapeutic effects on SCI and is safe; however, the clinical effects are limited at present. Therefore, new therapeutic agents, such as genetically enhanced stem cells which effectively secrete neurotrophic factors or cytokines, must be developed based on the safety of pure MSCs.

• 대한생식의학회:학술대회논문집
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• 2005.11a
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• pp.87-88
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• 2005

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.386-395
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• 2010

Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and $CoCl_2$. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of $CoCl_2$. Y27632 with high specificity for ROCK at 1-30 ${\mu}M$ was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100 ${\mu}M$, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including ${\beta}$-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.

• Molecules and Cells
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• v.38 no.4
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• pp.336-342
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• 2015

Propyl gallate (PG) used as an additive in various foods has antioxidant and anti-inflammatory effects. Although the functional roles of PG in various cell types are well characterized, it is unknown whether PG has effect on stem cell differentiation. In this study, we demonstrated that PG could inhibit adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells (hAMSCs) by decreasing the accumulation of intracellular lipid droplets. In addition, PG significantly reduced the expression of adipocyte-specific markers including peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$), CCAAT enhancer binding protein-${\alpha}$ (C/EBP-${\alpha}$), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein 2 (aP2). PG inhibited adipogenesis in hAMSCs through extracellular regulated kinase (ERK) pathway. Decreased adipogenesis following PG treatment was recovered in response to ERK blocking. Taken together, these results suggest a novel effect of PG on adipocyte differentiation in hAMSCs, supporting a negative role of ERK1/2 pathway in adipogenic differentiation.

• International Journal of Oral Biology
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• v.34 no.4
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• pp.177-183
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• 2009

Human mesenchymal stem cell (hMSCs) isolated from human adult bone marrow have self-renewal capacity and can differentiate into multiple cell types in vitro and in vivo. A number of studies have now demonstrated that MSCs can differentiate into various neuronal populations. Due to their autologous characteristics, replacement therapy using MSCs is considered to be safe and does not involve immunological complications. The basic helix-loop-helix (bHLH) transcription factor Olig2 is necessary for the specification of both oligodendrocytes and motor neurons during vertebrate embryogenesis. To develop an efficient method for inducing neuronal differentiation from MSCs, we attempted to optimize the culture conditions and combination with Olig2 gene overexpression. We observed neuron-like morphological changes in the hMSCs under these induction conditions and examined neuronal marker expression in these cells by RTPCR and immunocytochemistry. Our data demonstrate that the combination of Olig2 overexpression and neuron-specific conditioned medium facilitates the neuronal differentiation of hMSCs in vitro. These results will advance the development of an efficient stem cell-mediated cell therapy for human neurodegenerative diseases.

• International Journal of Oral Biology
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• v.37 no.1
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• pp.31-36
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• 2012

Dlx3 and Dlx5 are homeobox domain proteins and are well-known regulators of osteoblastic differentiation. Since possible reciprocal relationships between osteogenic and adipogenic differentiation in mesenchymal stem cells exist, we examined the regulatory role of Dlx3 and Dlx5 on adipogenic differentiation using human dental pulp stem cells. Over-expression of Dlx3 and Dlx5 stimulated osteogenic differentiation but inhibited adipogenic differentiation of human dental pulp stem cells. Dlx3 and Dlx5 suppressed the expression of adipogenic marker genes such as $C/EBP{\alpha}$, $PPAR{\gamma}$, aP2 and lipoprotein lipase. Adipogenic stimuli suppressed the mRNA levels of Dlx3 and Dlx5, whereas osteogenic stimuli enhanced the expression of Dlx3 and Dlx5 in 3T3-L1 preadipocytes. These results suggest that Dlx3 and Dlx5 exert a stimulatory effect on osteogenic differentiation of stem cells through the inhibition of adipogenic differentiation as well as direct stimulation.

• Development and Reproduction
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• v.13 no.4
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• pp.227-237
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• 2009

Recently, adipose mesenchymal stem cells (AdMSC) that are similar to bone marrow MSC and blood derived MSC are thought to be another source for stem cell therapy. However, the diseases that can be applied for stem cells therapy are age-dependent degenerative diseases. Accordingly, the present study investigated the growth and differentiation potential to neural cells of human AdMSC (hAdMSC) obtained from aged thirty, forty and fifty. The growth of cells and cell viability were measured by passage and neural differentiation of hAdMSC was induced in neural differentiation condition for 10 days. Our results demonstrated that cell number, viability and morphology were not different from hAdMSC by age and passage. Immunofluorescence analysis of neural cell marker (TuJ1, NSE, Sox2, GFAP or MAP2) demonstrated no significant differences in neural cell differentiation by age and passage. As the number of passage was increased, the mRNA level of MAP2 and Sox2 was decreased in hAdMSC from age of 50 compared to hAdMSC from age of 30. In conclusion, the present study demonstrated that ability of neural cell differentiation of hAdMSC was maintained with ages, suggesting that autologous stem cells from aged people can be applied for stem cell therapy with age-dependent neural disease with the same stem cell quality and ability as stem cell derived from young age.

• BMB Reports
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• v.56 no.2
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• pp.71-77
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• 2023

Cancers are one of the most dreaded diseases in human history and have been targeted by numerous trials including surgery, chemotherapy, radiation therapy, and anti-cancer drugs. Adult stem cells (ASCs), which can regenerate tissues and repair damage, have emerged as leading therapeutic candidates due to their homing ability toward tumor foci. Stem cells can precisely target malicious tumors, thereby minimizing the toxicity of normal cells and unfavorable side effects. ASCs, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs), are powerful tools for delivering therapeutic agents to various primary and metastatic cancers. Engineered ASCs act as a bridge between the tumor sites and tumoricidal reagents, producing therapeutic substances such as exosomes, viruses, and anti-cancer proteins encoded by several suicide genes. This review focuses on various anti-cancer therapies implemented via ASCs and summarizes the recent treatment progress and shortcomings.

• Journal of Acupuncture Research
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• v.23 no.5
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• pp.69-77
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• 2006

Background : Mesenchymal stem cells (MSCs) are present in most of the tissue matrix, taking part in their regeneration when injury or damage occurs. The aim of this study was to investigate the presence of cells with pluripotential characteristics in human subchondral bone and the capacity of these cells to differentiate to osteoblast. Methods : Human subchondral bone were digested with collagenase. Isolated cells were cultured with a-MEM, 15% FBS, 10-8M dexamethasone and 50 ng/mL ascoric acid. Cells from 0 day(isolated cells), 7 day (first subculture) and 14 days (third subculture) were used to carry out phenotypic characterization experiments flowcytometry analysis with 11 monoclonal antibodies) and osteogenic differentiation experiments. Osteogenic differentiation of cells was assessment by quantification of bone extracellular matrix components by following analysis: alkaline phosphatase(ALP) stains to detect ALP activity, RT-PCR and western blot to detect osteocalcin (OCN), osteopontin (OPN) and type I collagen(Col I), and Alizarin red stains to detect calcium deposition. Results : Flowcytometry analyses showed that in our population more than 98% of cells were positive for MSC markers: SH-2(CD105, 99%), CD29 (95%), CD73 (95%). Cells were negative for hematopoietic markers (CD11b, CD34, and CD45). Furthermore, cells showed positive stain to multipotent markers such as CDl17 (c-kit) (15.1%), and CD166 (74.9%), and cell adhesion molecules such as CD54 (78.1%) and CD106 (63.5%). The osteogenic specific marker analyses showed that the culture of these cells for 7 and 14 days stimulates ALP, OCN, OPN and Col I synthesis by RT-PCR and Western blot analysis. Also, after 14 days in the culture of MSCs induces mineralization by Arizarin red stain. Conclusion : In this work, we demonstrated a new and efficient method for osteoblastic differentiation of human subchondral bone stem cells. As MSCs takes part in reparative processes of adult tissues, these cells could play an important role in osteogenesis.

• 대한생식의학회:학술대회논문집
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• 2006.06a
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• pp.168.2-168.2
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• 2006