• Title/Summary/Keyword: organ regeneration

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Current status and prospects of organoid-based regenerative medicine

  • Woo Hee Choi;Dong Hyuck Bae;Jongman Yoo
    • BMB Reports
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    • v.56 no.1
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    • pp.10-14
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    • 2023
  • Organoids derived from stem cells or organ-specific progenitors are self-organizable, self-renewable, and multicellular three-dimensional (3D) structures that can mimic the function and structure of the derived tissue. Due to such characteristics, organoids are attracting attention as an excellent ex vivo model for drug screening at the stage of drug development. In addition, since the applicability of organoids as therapeutics for tissue regeneration has been embossed, the development of various organoids-based regenerative medicine has been rapidly progressing, reaching the clinical trial stage. In this review, we give a general overview of organoids and describe current status and prospects of organoid-based regenerative medicine, focusing on organoid-based regenerative therapeutics currently under development including clinical trials.

Plant Regeneration and in vitro Tuber Enlargement from Callus in Pinellia ternata(Thunb.) Breit (반하(半夏) 캘러스로부터 식물체(植物體) 재생(再生)과 기내(器內) 괴경(塊莖) 생장(生長) 유도(誘導))

  • Kim, Tai-Soo;Park, Moon-Soo;Park, Ho-Ki;Kim, Sun;Jang, Yeong-Sun
    • Korean Journal of Medicinal Crop Science
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    • v.2 no.3
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    • pp.246-250
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    • 1994
  • This study carried out to induce plant regeneration and callus formation from leaflet in MS medium with 2.4-D, NAL and IAA for in vitro growth of tuber, Kinetin and BA were used for plant regeneration. $NH_4NO_3$ and $KNO_3$ as a nitrogen source and $(NH_4)_2SO_4$, as a sulfate source were tested for in vitro growth of tuber. The resutls ars as fellows : 1. For the callus formation from leaflet and differentiation potency of organ, 2.4-D was more effective than IAA in MS medium under $26^{\circ}C$ and light condition of 8 hours a day. 2. For the plant regeneration from callus, MS medium with $2.0\;mg/{\ell}$ BA was most effective under $26^{\circ}C$ and light condition of $16{\sim}24$ hours a day. 3. For the in vitro growth of tuber, $KNO_3$ by $3.0g/{\ell}$ in MS medium was effective. This condition enhanced the growth of tuber 2.5 times compared with that in MS medium with $2.0\;mg/{\ell}$ BA.

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Postirradiation Synthesis and Degradation of DNA in Various Tissues of Rats (放射線을 照射한 흰쥐의 여러 가지 組織내의 DNA의 合成과 分解)

  • Kang, Man-Sik
    • The Korean Journal of Zoology
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    • v.14 no.4
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    • pp.199-204
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    • 1971
  • The effect of 400 R total-body X-irradiation on the rate of deoxycytidine-2-$^14 C$(CdR-2-$^14 C$) into DNA and on the degradation of DNA has been studied in the liver, spleen and thymus of the rat. The postirradiation period can be divided into a radiation reaction period followed by a regeneration period. During the period of radiation reaction, which consists of days 1-2, markdely decreased CdR-2-$^14 C$ incorporation into DNA of each organ is observed. Rate of incorporation of labeled precursor in the thymus shows the most profound decrease, whereas those in the liver and spleen show similar decrease when expressed as percent of normal. The change in the amount of DNA as percent of normal exhibits a similar pattern in all organs, but the rate of decrease is larger in the spleen and thymus compared to that in the liver. The period of regeneration as judged by the incorporation experiment appears day 4 to 5, which consists of the second phase of the regeneration period. The second phase is highlighted by a markedly increased rate of CdR-2-$^14 C$ incorporation and by a slow and continued increase in the amount of DNA in all organs. The regeneration occurs faster in the liver and spleen than in the thymus which is the most radiosensitive of the all. The findings of the present experiments are strongly suggestive of the fact that the radiation-induced loss of spleen and thymus DNA as well as the radiation-caused inhibition in the CdR incorporation into DNA of the thymus are the important factors in the elevated levels of CdR in the urine and plasma.

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Preparation and Release Behavior of Albumin-Loaded PLGA Scaffold by Ice Particle Leaching Method (얼음입자추출법을 이용한 알부민 함유 PLGA 담체의 제조 및 방출 거동)

  • Hong Keum Duck;Seo Kwang Su;Kim Soon Hee;Kim Sun Kyung;Khang Gilson;Shin Hyung Sik;Kim Moon Suk;Lee Hai Bang
    • Polymer(Korea)
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    • v.29 no.3
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    • pp.282-287
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    • 2005
  • A novel ice particle leaching method for fabrication of porous and biodegradable PLGA scaffold has been proposed for the application to tissue engineering. After uniform mixing of poly(L-lactide-co-glycolide) (PLGA) and bovine serum albumin-fluorescein isothiocyanate (FITC-BSA), the FITC-BSA loaded scaffold was fabricated by adding various ratio of ice particle. The release profiles of FITC-BSA were examined using pH 7.4 PBS for 28 days at $37^{circ}$. The release amount was determined by fluorescence intensity by using the fluorescence spectrophotometer and the morphological change of the scaffolds was observed by scanning electron microscope. The release initial burst of BSA containing scaffolds was lower than that of simple dipping scaffolds resulting in constant release aspect. Although the BSA concentration increased. the initial burst was not increased. As a result of this study, it can be suggested that ice particle leaching method for the tissue engineered scaffold miff be very useful and it is possible to impregnate with water soluble factors like cytokine. We suggest that ice particle leaching method may be useful to tissue engineered organ regeneration.

Three-Dimensional Printed 3D Structure for Tissue Engineering (3 차원 프린팅 기술로 제작된 조직공학용 3 차원 구조체)

  • Park, Jeong Hun;Jang, Jinah;Cho, Dong-Woo
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.38 no.10
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    • pp.817-829
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    • 2014
  • One of the main issues in tissue engineering has been the development of a three-dimensional (3D) structure, which is a temporary template that provides the structural support and microenvironment necessary for cell growth and differentiation into the target tissue. In tissue engineering, various biomaterials and their processing techniques have been applied for the fabrication of 3D structures. In particular, 3D printing technology enables the fabrication of a complex inner/outer architecture using a computer-aided design and manufacturing (CAD/CAM) system, and it has been widely applied to the fabrication of 3D structures for tissue engineering. Novel cell/organ printing techniques based on 3D printing have also been developed for the fabrication of a biomimetic structure with various cells and biomaterials. This paper presents a comprehensive review of the functional scaffold and cell-printed structures based on 3D printing technology and the application of this technology to various kinds of tissues regeneration.

Acute and Subchronic Inhalation Toxicity Evaluation of Methyl Formate in Rats (Methyl formate의 랫드를 이용한 급성 및 아만성 흡입독성 평가)

  • Kim, Hyeon-Yeong;Lee, Sung-Bae;Han, Jeong-Hee;Kang, Min-Gu;Yang, Jeong-Sun
    • Environmental Analysis Health and Toxicology
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    • v.25 no.2
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    • pp.131-143
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    • 2010
  • We performed the tests of acute and subchronic inhalation toxicity of methyl formate, which has limited toxicological data in spite of its widespread use and enhanced hazard consequent on its high volatility. The median lethal concentration ($LC_{50}$) was evaluated to be above 5,000ppm(12.27 mg/L). In the test with subchronic inhalation, there are no deaths, but with reduction of body weight, food intake, organ weight by exposure to 400 (0.98 mg/L) and 1,600 (3.92 mg/L) ppm, dose-dependently. There were statistical differences in some hematological and blood biochemical parameters as compared to control (e.g. neutrophile and lymphocyte in the 1,600 ppm group, calcium and A/G in 1,600 ppm group). Methyl formate under the exposure of 1,600 ppm showed the respiratory findings with nasal, it was confirmed that the chemical has respiratory hazard with 1,600 ppm inhalation exposure, induces nasal epithelial atrophy, olfactory cell degeneration/regeneration and the contraction of olfactory cells, etc. According to the notification with Ministry of Labor (No. 2009-68) for classification, labeling and MSDS of chemicals, it is suggested for methyl formate to be classified as category 4 in acute (10.0$4\leq20.0$ mg/L), category 2 (0.2$\leq$1.0 mg/L/6h, 90 days) in specific target organ-repeated exposure.

EST analysis of regenerating newt retina

  • Hisatomi, Osamu;Hasegawa, Akiyuki;Goto, Tatsushi;Yamamoto, Shintaro;Sakami, Sanae;Kobayashi, Yuko;Tokunaga, Fumio
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.267-268
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    • 2002
  • A vertebrate retina is an organ belonging to the central nerve system (CNS), and is usually difficult to regenerate except at an embryonic stage in life. However, certain species of urodele amphibians, such as newts and salamanders, possess the ability to regenerate a functional retina from retinal pigment epithelial (RPE) cells even as adults. After surgical removal of neural retinas from adult newt eyes, the remaining RPE cells lose their pigment granules, transdifferentiate into retinal progenitor cells, which further differentiate into various retinal neurons, and then finally reform a functional neural network. To understand the molecular mechanisms of CNS regeneration, we attempted to investigate the genes expressing in regenerating newt retina. mRNAs were isolated from regenerating retinas at 18-19 days after the surgical removal of the normal retina, and a cDNA library (regenerating retinal cDNA library) were constructed. Our EST analysis of 112 clones in the regenerating cDNA library revealed that about 70% clones are closely related to the genes previously identified. About 40% clones are housekeeping genes, and about 15% clones encode proteins related to the regulation of gene expression and to the proliferation of the cells. Sequences similar to neural retina- and RPE-specific genes were not detected at all. These results led us to suppose that the regenerating retinal cells are in a state considerably different from those of neither neural retina nor RPE cells.

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Characterization of human cardiac mesenchymal stromal cells and their extracellular vesicles comparing with human bone marrow derived mesenchymal stem cells

  • Kang, In Sook;Suh, Joowon;Lee, Mi-Ni;Lee, Chaeyoung;Jin, Jing;Lee, Changjin;Yang, Young Il;Jang, Yangsoo;Oh, Goo Taeg
    • BMB Reports
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    • v.53 no.2
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    • pp.118-123
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    • 2020
  • Cardiac regeneration with adult stem-cell (ASC) therapy is a promising field to address advanced cardiovascular diseases. In addition, extracellular vesicles (EVs) from ASCs have been implicated in acting as paracrine factors to improve cardiac functions in ASC therapy. In our work, we isolated human cardiac mesenchymal stromal cells (h-CMSCs) by means of three-dimensional organ culture (3D culture) during ex vivo expansion of cardiac tissue, to compare the functional efficacy with human bone-marrow derived mesenchymal stem cells (h-BM-MSCs), one of the actively studied ASCs. We characterized the h-CMSCs as CD90low, c-kitnegative, CD105positive phenotype and these cells express NANOG, SOX2, and GATA4. To identify the more effective type of EVs for angiogenesis among the different sources of ASCs, we isolated EVs which were derived from CMSCs with either normoxic or hypoxic condition and BM-MSCs. Our in vitro tube-formation results demonstrated that the angiogenic effects of EVs from hypoxia-treated CMSCs (CMSC-Hpx EVs) were greater than the well-known effects of EVs from BM-MSCs (BM-MSC EVs), and these were even comparable to human vascular endothelial growth factor (hVEGF), a potent angiogenic factor. Therefore, we present here that CD90lowc-kitnegativeCD105positive CMSCs under hypoxic conditions secrete functionally superior EVs for in vitro angiogenesis. Our findings will allow more insights on understanding myocardial repair.

Establishment of Genetic Transformation System and Introduction of MADS Box Gene in Hot Pepper (Capsicum annuum L.)

  • Lim, Hak-Tae;Zhao, Mei-Ai;Lian, Yu-Ji;Lee, Ji-Young;Eung-Jun park;Chun, Ik-Jo;Yu, Jae-Woong;Kim, Byung-Dong
    • Journal of Plant Biotechnology
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    • v.3 no.2
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    • pp.89-94
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    • 2001
  • In vitro plant regeneration of inbred breeding line of hot pepper (Capsicum annuum L.) was established using leaf and petiole segments as explants. About 28 days old plants were excised and cultured on MS medium supplemented with TDZ and NAA or in combination with Zeatin. In all of the media compositions tested, combination of TDZ 0.5 mg/L, Zeatin 0.5 mg/L, and NAA 0.1 mg/L was found to be the best medium for shoot bud initiation. Young petiole was the most appropriate explant type for the plant regeneration as well as genetic transformation in hot pepper. In this study, HpMADS1 gene isolated from hot pepper was introduced using Agrobacterium-mediated transformation system. Based on the analysis of Southern blot and RT-PCR, HpMADS1 gene was integrated in the hot pepper genome. It has been known that floral organ development is controlled by a group of regulatory factors containing the MADS domain. Morphological characteristics in these transgenic plants, especially flowering habit, however, were not significantly altered, indicating this MADS gene, HpMADS1 may be non-functional in this case.

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Cell Versus Chemokine Therapy Effects on Cell Mobilization to Chronically Dysfunctional Urinary Sphincters of Nonhuman Primates

  • Williams, J. Koudy;Mariya, Silmi;Suparto, Irma;Lankford, Shannon S.;Andersson, Karl-Erik
    • International Neurourology Journal
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    • v.22 no.4
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    • pp.260-267
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    • 2018
  • Purpose: A major question remaining in approaches to tissue engineering and organ replacement is the role of native mobilized native cells in the regeneration process of damaged tissues and organs. The goal of this study was to compare the cell mobilizing effects of the chemokine CXCL12 and cell therapy on the urinary sphincter of nonhuman primates (NHP) with chronic intrinsic urinary sphincter dysfunction. Methods: Either autologous lenti-M-cherry labeled skeletal muscle precursor cells (skMPCs) or CXCL12 were injected directly into the sphincter complex of female NHPs with or without surgery-induced chronic urinary sphincter dysfunction (n=4/treatment condition). All monkeys had partial bone marrow transplantation with autologous lenti-green fluorescent protein (GFP) bone marrow cells prior to treatment. Labeled cells were identified, characterized and quantified using computer-assisted immunohistochemistry 6 months posttreatment. Results: GFP-labeled bone marrow cells (BMCs) were identified in the bone marrow and both BMCs and skMPCs were found in the urinary sphincter at 6-month postinjection. BMCs and skMPCs were present in the striated muscle, smooth muscle, and lamina propria/urothelium of the sphincter tissue. Sphincter injury increased the sphincter content of BMCs when analyzed 6-month postinjection. CXCL12 treatment, but not skMPCs, increased the number of BMCs in all layers of the sphincter complex (P<0.05). CXCL12 only modestly (P=0.15) increased the number of skMPCs in the sphincter complex. Conclusions: This dual labeling methodology now provides us with the tools to measure the relative number of locally injected cells versus bone marrow transplanted cells. The results of this study suggest that CXCL12 promotes mobilization of cells to the sphincter, which may contribute more to sphincter regeneration than injected cells.