Effect of Neurotrophic Factors on Neuronal Stem Cell Death

KimKwon, Yun-Hee Korean Society for Biochemistry and Molecular Biol 2002 Journal of biochemistry and molecular biology Vol.35 No.1

Neural cell survival is an essential concern in the aging brain and many diseases of the central nervous system. Neural transplantation of the stem cells are already applied to clinical trials for many degenerative neurological diseases, including Huntington's disease, Parkinson's disease, and strokes. A critical problem of the neural transplantation is how to reduce their apoptosis and improve cell survival. Neurotrophic factors generally contribute as extrinsic cues to promote cell survival of specific neurons in the developing mammalian brains, but the survival factor for neural stem cell is poorly defined. To understand the mechanism controlling stem cell death and improve cell survival of the transplanted stem cells, we investigated the effect of plausible neurotrophic factors on stem cell survival. The neural stem cell, HiB5, when treated with PDGF prior to transplantation, survived better than cells without PDGF. The resulting survival rate was two fold for four weeks and up to three fold for twelve weeks. When transplanted into dorsal hippocampus, they migrated along hippocampal alveus and integrated into pyramidal cell layers and dentate granule cell layers in an inside out sequence, which is perhaps the endogenous pathway that is similar to that in embryonic neurogenesis. Promotion of the long term-survival and differentiation of the transplanted neural precursors by PDGF may facilitate regeneration in the aging adult brain and probably in the injury sites of the brain.

DJ-1 Gene Promote Cell Survival against Oxidative Stress in Canine

Eun Young Kim,Kang Sun Park,Bo Myeong Lee,Lili Zhuang,Dong Ern Kim,Eun Do Lee,Chi Sun Yun,Ji Hye Lee,Ju Lan Chun,Min Kyu Kim 한국수정란이식학회 2016 한국수정란이식학회 학술대회 Vol.2016 No.10

The cancer and Parkinson's disease associated protein DJ-1 is multifunctional protein that involves in diverse cellular process. DJ-1 protein has a cellular protective role and promoted cell survival under an oxidative stress. However, the cellular protective mechanism of DJ-1 is not fully understand, and we needs to be further study their functions in novel organisms. In the present study, we investigated the protective role of DJ-1 against induced oxidative stress in canine cell line. On the basis of these experiments, canine DJ-1 overexpressing and null cell lines were established. The stable overexpression and down regulation of DJ-1 efficiency confirmed by the western blot analysis. Subsequently, the DJ-1 gene transfected cell lines and control cells were subjected to induced the oxidative stress, and then cell viability, cell proliferation assay, cellular apoptosis detection analysis (Annexin V and TUNEL assay), intracellular ROS and mitochondrial activity were measured appropriately. The results showed that DJ-1 overexpressed cells were up-regulated cell viability under oxidative stress conditions induced by the rotenone and hydrogen peroxide (H2O2), whereas loss of DJ-1 cells were down-regulated the cell survival activity. Additionally, overexpression of DJ-1 cells increased cell resistance to oxidative stress and inhibited the elevation of cell death and cellular ROS induced apoptosis. Moreover, DJ-1 overexpressed cells was increased mitochondrial functions by using confocal microscopy with MitoTracker staining. On the contrary to this, DJ-1 null cells show defective cellular protection and mitochondria activity against oxidative stress conditions. Our data indicate that canine DJ-1 protein attenuates cellular apoptosis and ROS generation, enhances the cellular survival activity and promote mitochondrial function under the oxidative stress, likewise other mammalian cells. Importantly, DJ-1 overexpression may be an important part of a protective strategy as a sensor for oxidative stress.

Effects of ginsenoside on survival of human embryonic stem cell-derived cardiac cells after thawing

Jun Beom Ku,Yoon Young Kim,Sun Kyung Oh,Seok Hyun Kim,Young Min Choi,Shin Yong Moon 한국발생생물학회 2012 한국발생생물학회 학술발표대회 Vol.31 No.-

Human embryonic stem cells (hESCs) are promising cell source because of their unique self-renewal and pluripotency. Although hESC-derived cardiac cells are currently generated worldwide, cryopreservation of these cells is still limited due to low rate of post-thaw survival. Cryopreservation of hESC-derived cardiac cells is critical in that their long-term storage can accelerate their use in regenerative medicine. However, to date, there are few reports on efficient cryopreservation and post-thaw survival of hESC-derived cardiac cells. In this study, we evaluated the effects of ginsenoside, which is known to improve survival of rat embryonic cardiomyocytes against myocardial ischemia injury in diabetic rats (Wu et al., 2011), on the survival of hESC-derived cardiac cells after thawing. We induced differentiation into cardiac cells using our previously reported method (Kim et al., 2011). Differentiated, pre-beating stage cardiac cells were cryopreserved using either mass cryopreservation or vitrification. To evaluate the effects of ginsenoside (Re, Rb), we compared three sets: pre- and post-thaw treatment, pre- or post-thaw treatment only. The survival of post-thaw cardiac cells were evaluated using Trypan-blue and Annexin V staining. In addition, the three groups were treated with ROCK inhibitor Y-27632, and compared with non-treatment groups. The effect of ginsenoside was significant in post-thaw treatment group, i.e, thawed cells expressed cardiac specific genes and showed specific functionality such as spontaneous beating. Taken together, we demonstrated favorable effects of ginsenoside on the survival of hESC-derived cardiac cells after cryopreservation and thawing. These results suggest a possible application of well-known cardioprotectant ginsenoside in cell-based tissue engineering using hESC-derived cardiac cells.

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

Shafiq, M.,Jung, Y.,Kim, S.H. IPC Science and Technology Press 2016 Biomaterials Vol.90 No.-

<P>Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transplanted cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. Therefore, in order to maximize the clinical utility of stem/progenitor cells, strategies must be employed to increase their adhesion, retention, and engraftment in vivo. Here, we reviewed key strategies that are being adopted to enhance the survival, retention, and engraftment of transplanted stem cells through the manipulation of both the stem cells and the surrounding environment. We describe how preconditioning of cells or cell manipulations strategies can enhance stem cell survival and engraftment after transplantation. We also discuss how biomaterials can enhance the function of stem cells for effective tissue regeneration. Biomaterials can incorporate or mimic extracellular function (ECM) function and enhance survival or differentiation of transplanted cells in vivo. Biomaterials can also promote angiogenesis, enhance engraftment and differentiation, and accelerate electromechanical integration of transplanted stem cells. Insight gained from this review may direct the development of future investigations and clinical trials. (C) 2016 Elsevier Ltd. All rights reserved.</P>

CD43 Expression Regulated by IL-12 Signaling Is Associated with Survival of CD8 T Cells

Lee, Jee-Boong,Chang, Jun The Korean Association of Immunobiologists 2010 Immune Network Vol.10 No.5

Background: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. Methods: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified $CD43^{lo}$ and $CD43^{hi}$ cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. Results: Compared to $CD43^{hi}$ effector cells, $CD43^{lo}$ effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. $CD43^{lo}$ effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of $CD43^{lo}$ CD8 T cells was also partly associated with CD62L expression. Conclusion: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.

CD43 Expression Regulated by IL-12 Signaling Is Associated with Survival of CD8 T Cells

장준,이지붕 대한면역학회 2010 Immune Network Vol.10 No.5

In addition to TCR and costimulatory signals,cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. Methods: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified CD43lo and CD43hi cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. Results: Compared to CD43hi effector cells, CD43lo effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. CD43lo effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of CD43lo CD8 T cells was also partly associated with CD62L expression. Conclusion: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.

지방유래 줄기세포의 생존능 향상을 위한 CEACAM 6의 생물학적기능에 대한 연구

고은영,유지은,정세화,김평환 대한임상검사과학회 2019 대한임상검사과학회지(KJCLS) Vol.51 No.4

세포기반 치료제에 사용되는 줄기세포는 재생능력과 다양한세포로의 분화능력으로 인해 재생 의학 분야에서 광범위하게 관심을 끌었으며, 많은 불치병에 적용된다. 하지만, 이러한 줄기세포는 여전히 치료 전 세포증식 및 질병 투여부위에서의 낮은 생존률로 인해 충분한 치료효과가 나타나지 않는 단점이 있다. 이것을 해결하고자, 우리는 세포부착능과 항세포자살 기능을 가지고 있는 carcinoembryonic antigen (CEA) gene family 의 하나인 CEACAM 6를 사용하였다. 이것을 줄기세포에 적용전, 먼저 세포별로 이 단백질이 발현되는지를 확인하였고, 이 유전자가 발현되는 벡터를 줄기세포에 삽입시키기 위한 최적 조건을 선정하였다. 그 후, 도입된 CEACAM 6발현벡터로부터 줄기세포에서 이 유전자가 발현되는지를 확인하였다. 그리고 인체투여 시 발생되는 산화적 스트레스와 유사한 조건에서의 이 유전자의 기능을 평가하기 위해 과산화수소(H2O2)를 처리하였다. 산화적 스트레스 조건하에서 CEACAM 6가 발현되는 줄기세포는 그렇지 않은 세포에 비해 세포의 생존률이 현저히 증가하는것을 확인하였다. 이를 통해, 이 CEACAM 6는 줄기세포의 치료효능과 세포증식을 강화시킬 수 있는 다른 선택지로서의 가능성이 있음을 확인하였다. The use of stem cells in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it has been applied to numerous incurable diseases due to the inherent abilities of self-renewal and differentiation. However, there still exist some severe obstacles, such as requirement of cell expansion before the treatment, and low survival at the treated site. To overcome these disadvantages of stem cells, we used the carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM 6) gene, which functions to increase cell-cell interaction as well as anti-apoptosis. We first confirmed whether CEACAM 6 is expressed in various cell lines at the protein level (including in stem cells), followed by evaluating and selecting the optimal transfection conditions into stem cells. The CEACAM 6 gene was transfected into stem cells to prolong cell survival and preserve from damage by oxidative stress. After confirming the CEACAM 6 expression in transfected stem cells, the cell survival was assessed under oxidative condition by exposing to hydrogen peroxide (H2O2) to mimic the chronic environment-induced cellular damage. CEACAM 6 expressing stem cells show increased cell viability compared to the non-CEACAM 6 expressing cells. We propose that the application of the CEACAM 6 gene is a potential option, capable of expanding and enhancing the therapeutic effects of stem cells.

Season of Diagnosis and Survival of Advanced Lung Cancer Cases - Any Correlation?

Oguz, Arzu,Unal, Dilek,Kurtul, Neslihan,Aykas, Fatma,Mutlu, Hasan,Karagoz, Hatice,Cetinkaya, Ali Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Introduction: The influence of season at diagnosis on cancer survival has been an intriguing issue for many years. Most studies have shown a possible correlation in between the seasonality and some cancer type survival. With short expected survival, lung cancer is an arena that still is in need of new prognostic factors and models. We aimed to investigate the effect of season of diagnosis on 3 months, 1 and 2 years survival rates and overall survival of non small cell lung cancer patients. Materials and Methods: The files of non small cell lung cancer patients that were stages IIIB and IV at diagnosis were reviewed retrospectively. According to diagnosis date, the patients were grouped into 4 season groups, autumn, winter, spring and summer. Results: A total of 279 advanced non small cell lung cancer patients' files were reviewed. Median overall survival was 15 months in the entire population. Overall 3 months, 1 and 2 years survival rates were 91.0%, 58.2% and 31.2% respectively. The season of diagnosis was significantly correlated with 3 months survival rates, being diagnosed in spring being associated with better survival. Also the season was significantly correlated with T stage of the disease. For 1 and 2 years survival rates and overall survival, the season of diagnosis was not significantly correlated. There was no correlation detected between season and overall survivals according to histological subtypes of non small cell lung cancer. Conclusion: As a new finding in advanced non small cell lung cancer patients, it can be concluded that being diagnosed in spring can be a favorable prognostic factor for short term survival.

P097 : Secondary cutaneous lymphoma: a comparative clinical features and survival outcome analysis of 106 cases according to cell lineage of lymphoma

( Sang Hyung Lee ),( Woo Jin Lee ),( Kwang Hee Won ),( Chong Hyun Won ),( Sung Eun Chang ),( Jee Ho Choi ),( Kee Chan Moon ),( Mi Woo Lee ),( Chan Sik Park ),( Joor Yung Huh ),( Cheol Won Suh ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: The relative frequency, clinical features, and survival outcomes of secondary cutaneous lymphoma remain poorly understood. Objectives: To determine the clinical characteristics and survival outcomes of secondary cutaneous lymphoma. Methods: The present retrospective cohort study included all 106 patients who presented with secondary cutaneous lymphoma. Patient medical records were reviewed to determine the clinical features, survival outcomes, and prognostic factors. Results: Secondary cutaneous lymphomas consisted of mature T-/NK-cell lymphomas (56%), mature B-cell lymphomas (35%), immature hematopoietic malignancies (8%), and Hodgkin lymphoma (1%). The lymphoma cell lineage did not significantly influence survival, even though T-/NK-cell lymphoma skin lesions were more extensive than B-cell lymphoma skin lesions. Prognostic factors that associated with poor survival were elevated lactate dehydrogenase at the time of initial staging, extranodal lymphoma, disseminated skin lesions, and an early (<6 months) development of skin lesions after the initial diagnosis. The two lymphoma cell lineages differed in terms of prognostic factors that influenced survival. Conclusion: Skin lesion characteristics such as time point of appearance and extent affect the survival outcomes of secondary cutaneous lymphoma. Cell lineage did not influence survival outcomes but the two lineages associated with different prognostic factors.

산화철 나노입자의 U373MG 세포 독성평가 및 방사선 세포생존 곡선에 미치는 영향에 대한 연구

강성희(Seonghee Kang),김정환(Jeonghwan Kim),김도경(Dokyung Kim),강보선(Bosun Kang) 한국방사선학회 2012 한국방사선학회 논문지 Vol.6 No.6

본 연구는 초상자성 산화철 나노입자 (SPIONs)의 세포독성평가 및 SPIONs를 uptake한 뇌신경교종 (glioblastoma multiforme, GBM) 세포의 방사선 세포생존곡선을 구하기 위해 수행되었으며, 본 연구의 결과는 양성자선과 SPIONs 이용한 GBM의 양성자선 치료선량 정보 등 양성자선 치료효과를 개선하기 위한 기초자료로 활용될 수 있을 것이다. SPIONs의 세포독성을 평가는 in vitro 실험 후 MTT 분석법을 이용하여 수행하였다. 독성평가 결과 1~100㎍/ml의 농도에서는 세포생존율의 유의한 차이가 나타나지 않았다. 하지만 200㎍/ml의 농도에서는 세포생존율이 74.2%로 감소 하며 세포독성을 나타냈다. SPIONs가 uptake 된 U373MG세포와 uptake 되지 않은 U373MG세포에 0~5 Gy의 양성자선을 조사하여 각각에 대한 세포생존곡선을 측정한 결과를 분석하여 SPIONs가 uptake된 U373MG세포의 세포생존율이 더 급격히 감소함을 알 수 있었다. 결론적으로 SPIONs가 uptake 된 세포에서는 보다 적은 선량으로도 세포사멸을 유도할 수 있음을 알 수 있었다. 따라서 GBM에 SPIONs를 타겟팅하면 양성자선을 이용한 뇌신경교종 치료효과를 개선할 수 있음을 보였다. This research was performed to evaluate the superparamagnetic iron oxide nanoparticles’(SPIONs) cell toxicity and to measure the radiation cell survival curve changes of SPIONs-uptake glioblastoma multiforme cells. The results could be practically used as the fundamental data to ameliorate proton beam cancer therapy, for example, providing necessary GBM treatment dose in the proton beam therapy when the therapy takes advantage of SPIONs. The assessment of the toxicological evaluation of synthesized SPIONs was accomplished by MTT assay as an in vitro experiment. The results showed no meaningful differences in the cell survival rate at the 1-100㎍/ml SPIONs concentrations, but the cell toxicity was shown as the cell survival rate decreased up to 74.2% at the 200㎍/ml SPIONs concentration. Then, we measured each radiation cell survival curve for U373MG cells and SPIONs-uptake U373MG cells with 0~5 Gy of proton beam irradiations. It is learned from the analysis of the experimental results that the SPION-uptake cells’ radiation survival rate was more rapidly decreased as the irradiation dose increased. In conclusion we confirmed that SPIONs-uptake in U373MG cells induces cell death at the much less dose than the lethal dose of SPION-non-uptake cell. This research shows that the therapeutic efficacy of glioblastoma multiforme treatment in proton beam therapy can be improved by SPIONs targeting to the GBM cells.