• Journal of Korean Neurosurgical Society
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• v.40 no.4
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• pp.267-272
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• 2006

Objective : There have been recent reports that mesenchymal stromal cells that are harvested from adipose tissue are able to differentiate into neurons. In the present study, we administered adipose tissue derived stem cells in rats with cerebral infarction in order to determine whether those stem cells could enhance the recovery of motor function. Methods : Cerebral infarction was induced by intraluminal occlusion of middle cerebral artery in rats. The adipose tissue-derived mesenchymal stem cells were harvested from inguinal fat pad and proliferated for 2 weeks in DMEM media. Approximately $1{\times}10^6$ cells were injected intravenously or into subdural space of the peri-lesional area. The rotor rod test was performed at preoperative state[before MCA occlusion], and 1, 2, 3, 4, 6, 8 and 10 weeks after the cell therapy. Results : The motor functions that were assessed by rotor rod test at 1 week of the cell therapy were nearly zero among the experimental groups. However, there was apparent motor function recovery after 2 weeks and 4 weeks of cell injection in intravenously treated rats and peri-lesionaly treated rats, respectively, while there was no significant improvement till 8 weeks in vehicle treated rats. Conclusion : These results demonstrate that the adipose derived stem cell treatment improves motor function recovery in rats with cerebral infarction.

• Journal of Korean Neurosurgical Society
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• v.62 no.5
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• pp.493-501
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• 2019

The generation of human induced pluripotent stem cells (iPSCs) from somatic cells using gene transfer opens new areas for precision medicine with personalized cell therapy and encourages the discovery of essential platforms for targeted drug development. iPSCs retain the genome of the donor, may regenerate indefinitely, and undergo differentiation into virtually any cell type of interest using a range of published protocols. There has been enormous interest among researchers regarding the application of iPSC technology to regenerative medicine and human disease modeling, in particular, modeling of neurologic diseases using patient-specific iPSCs. For instance, Parkinson's disease, Alzheimer's disease, and spinal cord injuries may be treated with iPSC therapy or replacement tissues obtained from iPSCs. In this review, we discuss the work so far on generation and characterization of iPSCs and focus on recent advances in the use of human iPSCs in clinical setting.

• BMB Reports
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• v.48 no.12
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• pp.702-707
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• 2015

To overcome the disadvantages of stem cell-based cell therapy like low cell survival at the disease site, we used stanniocalcin 2 (STC2), a family of secreted glycoprotein hormones that function to inhibit apoptosis and oxidative damage and to induce proliferation. STC2 gene was transfected into two kinds of stem cells to prolong cell survival and protect the cells from the damage by oxidative stress. The stem cells expressing STC2 exhibited increased cell viability and improved cell survival as well as elevated expression of the pluripotency and self-renewal markers (Oct4 and Nanog) under sub-lethal oxidative conditions. Up-regulation of CDK2 and CDK4 and down-regulation of cell cycle inhibitors p16 and p21 were observed after the delivery of STC2. Furthermore, STC2 transduction activated pAKT and pERK 1/2 signal pathways. Taken together, the STC2 can be used to enhance cell survival and maintain long-term stemness in therapeutic use of stem cells.

• BMB Reports
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• v.55 no.1
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• pp.30-38
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• 2022

Cardiovascular disease, especially ischemic heart disease, is a major cause of mortality worldwide. Cardiac repair is one of the most promising strategies to address advanced cardiovascular diseases. Despite moderate improvement in heart function via stem cell therapy, there is no evidence of significant improvement in mortality and morbidity beyond standard therapy. The most salutary effect of stem cell therapy are attributed to the paracrine effects and the stem cell-derived exosomes are known as a major contributor. Hence, exosomes are emerging as a promising therapeutic agent and potent biomarkers of cardiovascular disease. Furthermore, they play a role as cellular cargo and facilitate intercellular communication. However, the clinical use of exosomes is hindered by the absence of a standard operating procedures for exosome isolation and characterization, problems related to yield, and heterogeneity. In addition, the successful clinical application of exosomes requires strategies to optimize cargo, improve targeted delivery, and reduce the elimination of exosomes. In this review, we discuss the basic concept of exosomes and stem cell-derived exosomes in cardiovascular disease, and introduce current efforts to overcome the limitations and maximize the benefit of exosomes including engineered biomimetic exosomes.

• Journal of Life Science
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• v.30 no.7
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• pp.651-659
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• 2020

Cardiovascular disease is one of the leading causes of death across the world, and gold-standard treatments such as percutaneous coronary intervention and artery bypass grafting have various limitations including myocardial damage and subsequent maladaptive cardiac remodeling. To overcome this, stem-cell therapies are emerging as a promising strategy for cardiovascular regeneration. Endothelial progenitor cells (EPCs) have high potential to proliferate and differentiate into endothelial cells for vascularization and tissue regeneration, and several clinical trials have explored EPC function in tissue repair in relation to clinical safety and improving cardiac function. Consequently, EPC has been suggested as a feasible stem-cell therapy. However, autologous EPC transplantation in cardiovascular disease patients is restricted by risk factors such as age, smoking status, and hypertension that lead to reduced bioactivity in the EPCs. New approaches for improving EPC function and stem-cell efficacy have therefore been suggested, including cell priming, organoid culture systems, and enhancing transplantation efficiency through 3D bioprinting methods. In this review, we provide a comprehensive understanding of EPC characteristics, therapeutic approaches, and the current state of clinical research into EPCs as stem-cell therapy for cardiovascular disease.

• Journal of Life Science
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• v.24 no.11
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• pp.1238-1243
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• 2014

Mesenchymal stem cells (MSCs) have been widely used as cellular therapeutic agents. They have their own characteristic stemness, and thus, they can be used in the treatment of many chronic diseases and in anticancer therapy. MSC therapy has many advantages over chemical therapy. MSC therapy is based on self or homogeneous origin; as such, it is expected to be effective in the treatment of various diseases. In addition, microRNAs in particular have been studied for their structure and function, and they are also expected to prove effective for use as therapeutic agents in cancer or chronic diseases. MicroRNAs are largely associated with metabolism and homeostasis. Therefore, over- or under-expression of microRNAs leads to chronic diseases. Conversely, effective control of the expression of specific microRNAs reduces the risk of many chronic diseases. However, there have been no reports thus far on the synergistic effects of MSCs and microRNAs. Therefore, in this study, we examined the relationship between MSCs and microRNAs using placenta-derived MSCs (PDSCs), bone marrow-derived MSCs (BM-MSCs), and fibroblast (WI-38) cells. We studied the expression of some microRNAs in MSCs and compared the expression in each cell line and cell passage. As a result, we found that the expression of microRNA-34a was higher in PDSCs than in BM-MSCs and that the expression of microRNA-27a, 33a, 33b, and 211 was higher in BM-MSCs than in PDSCs. Therefore, we expect that each MSC line will be used as cell therapy, considering its expressed functional microRNA.

• Journal of Yeungnam Medical Science
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• v.19 no.1
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• pp.11-27
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• 2002

Allogenic hematopoietic stem cell transplantation is one of the effective therapy for several hematologic malignancies. Transplantation preparative regimen is designed to eradicate the patient's underlying disease and immunosuppress the patient adequately to prevent rejection of donor's hematopoietic stem cells. So, conventional myeloablative preparative regimens with high-dose chemotherapy or radiotherapy are related to high rate of morbidity and mortality. However, It has become clear that the high-dose therapy dose not eradicate the malignancy in some patients, and that the therapeutic benefit of allogenic transplantation is largely related to graft-versus-leukemia/graft-versus-tumor (GVL/GVT) effect. An new approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow GVL/GVT effects to develop. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly and those with comorbidities that preclude high-dose chemoradiotherapy.

• Medical Lasers
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• v.9 no.2
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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.

• Tuberculosis and Respiratory Diseases
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• v.80 no.1
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• pp.1-10
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• 2017

Chronic obstructive pulmonary disease (COPD) is a critical condition with high morbidity and mortality. Although several medications are available, there are no definite treatments. However, recent advances in the understanding of stem and progenitor cells in the lung, and molecular changes during re-alveolization after pneumonectomy, have made it possible to envisage the regeneration of damaged lungs. With this background, numerous studies of stem cells and various stimulatory molecules have been undertaken, to try and regenerate destroyed lungs in animal models of COPD. Both the cell and drug therapies show promising results. However, in contrast to the successes in laboratories, no clinical trials have exhibited satisfactory efficacy, although they were generally safe and tolerable. In this article, we review the previous experimental and clinical trials, and summarize the recent advances in lung regeneration therapy for COPD. Furthermore, we discuss the current limitations and future perspectives of this emerging field.

• Molecules and Cells
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• v.24 no.1
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.