• BMB Reports
• /
• 제54권7호
• /
• pp.356-367
• /
• 2021

Cell-based therapy is a promising approach in the field of regenerative medicine. As cells are formed into spheroids, their survival, functions, and engraftment in the transplanted site are significantly improved compared to single cell transplantation. To improve the therapeutic effect of cell spheroids even further, various biomaterials (e.g., nano- or microparticles, fibers, and hydrogels) have been developed for spheroid engineering. These biomaterials not only can control the overall spheroid formation (e.g., size, shape, aggregation speed, and degree of compaction), but also can regulate cell-to-cell and cell-to-matrix interactions in spheroids. Therefore, cell spheroids in synergy with biomaterials have recently emerged for cell-based regenerative therapy. Biomaterials-assisted spheroid engineering has been extensively studied for regeneration of bone or/and cartilage defects, critical limb ischemia, and myocardial infarction. Furthermore, it has been expanded to pancreas islets and hair follicle transplantation. This paper comprehensively reviews biomaterials-assisted spheroid engineering for regenerative therapy.

• Toxicological Research
• /
• 제22권3호
• /
• pp.301-306
• /
• 2006

Microcystin-LR(MC-LR), a cyanobacterial toxin produced by Microcystis aeruginosa, causes severe hepatotoxicity. Here we investigated the morphologic changes of rat hepatocyte spheroid induced by exposure of MC-LR($10^{-6}M$) in vitro. In addition, to determine the effects of such toxin in the process of hepatocyte spheroid formation, primarily isolated hepatocytes were incubated with MC-LR and the process of spheroid formation was observed. In both hepatocyte spheroid and suspension culture systems, the morphologic changes caused by MC-LR were noticible at 5 min post exposure and were characterized by the loss of microvilli, cytoplasmic vacuolation, the accumulation of lipid droplets, and blob formation. Especially, the size and numbers of blob on the cell surface were increased as the incubation time prolonged and the appearance of electron dense bodies were observed in the cytoplasm of hepatocyte at 20 min post exposure. Furthermore, bile canaliculi-like structures in the hepatocyte spheroids were slightly widened and the process of spheroids formation was inhibited in the isolated hepatocytes incubated with MC-LR. These results indicate that morphologic changes in. the hepatocyte membrane and organelles seem to be typical events in showing the MC-LR induced hepatotoxic effects and the spheroid culture method might be a useful experimental tool to evaluate hepatoxicity since it reflects the in vivo status of hepatocytes.

• 천문학논총
• /
• 제7권1호
• /
• pp.231-253
• /
• 1992

A model for the distribution of stars in the disk and the spheroid of our Galaxy is reexamined from an edge-on view of the Galaxy obtained by selecting infrared sources from the IRAS Point Source Catalog. The sources are counted as a function of galactic latitude. longitude and $12{\mu}m$ apparent magnitude. The source counts are reasonably separated into the disk component and the spheroid component contributions and each of the contributions is further interpreted as a convolution of a spatial density distribution and a luminosity function based on the least-square fit method. The spatial density of the disk component has an exponential radial scale length of $h_R{\sim}2.6\;kpc$ and the vertical distribution follows a canonical $sech^2$ law with a scale height $h_z{\sim}240\;pc$. The distribution of the spheroid component can be represented by an oblate spheriod with an axis ratio $k{\sim}0.61$ and a de Vaucouleurs' $r^{1/4}$ law with an effective radius of $R_e{\sim}120\;pc$. The steep density gradient of the spheroid component is consistent with that of late M giants in the central bulge. The luminosity functions of the disk and the spheroid component stars resemble respectively those of the K luminosity function of disk M giants (Garwood and Jones 1986) and the bolometric luminosity function of M giants in bulge fields (Frogel et al, 1990).

• KSBB Journal
• /
• 제7권4호
• /
• pp.278-283
• /
• 1992

쥐 간세포를 분리하고 여러가지 물질로 표면이 처리된 용기를 이용하여 배양하였다. 표면처리를 하지 않았을 경우와 collagen으로 처리하였을 경우 간세포는 monolayer형태를 이루며 자랐고, heparin과 hyaluronic acid의 경우에는 multilayer, 그리고 proteoglycan, dermatan sulfate(D. S.), BSA의 경우에는 hemispheroid, 그리고 표면처리를 하지 않은 Primaria는 spheroid형태를 형성하였다. 세포 생존도 면에서는 monolayer가 우수하였고, 간세포의 중요한 대사능이라고 볼 수 있는 암모니아의 제거능이나 albumin생산성 면에서는 hemispheroid 혹은 spheroid가 우수하였다.

• BMB Reports
• /
• 제50권2호
• /
• pp.79-84
• /
• 2017

Emphysema, a pathologic component of the chronic obstructive pulmonary disease, causes irreversible destruction of lung. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in mice with elastase-induced emphysema. ASCs were administered via an intrapleural route. Mice injected with spheroid ASCs showed improved regeneration of lung tissues, increased expression of growth factors such as fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF), and a reduction in proteases with an induction of protease inhibitors when compared with mice injected with dissociated ASCs. Our findings indicate that spheroid ASCs show better regeneration of lung tissues than dissociated ACSs in mice with elastase-induced emphysema.

• BMB Reports
• /
• 제56권4호
• /
• pp.225-233
• /
• 2023

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

• 대한의생명과학회지
• /
• 제12권3호
• /
• pp.153-160
• /
• 2006

Human colon cancer is the second most fatal disease among a variety of cancers to cause cancer death in U.S.A. and its incidence rate is currently increased in Korea. Recently, many studies have been being progressed on the efficacy of diverse combination treatments. But results of these studies in vitro were not similar those in vivo. This study compared the anticancer reactions between each use of arsenic trioxide and taxol against human colon cancer HT-29 cell line and combined use of two drugs. And these results compared with the results of HT-29 spheroid cells having similar characteristics to the solid tumor in vivo. The spheroid of HT-29 cells was formed by using a multicellular spheroid system and the result was observed through electron microscopy. In vitro cytotoxicity of each use of arsenic trioxide and taxol was evaluated in HT-29 monolayer cells. The $IC_{50}$ value for arsenic trioxide was to be $33{\mu}M$ and taxol was to be 18nM. The result treated with the combination of taxol and arsenic trioxide decreased the cytotoxicity on the HT-29 monolayer cells. The spheroid cells represented higher resistance against drugs than the monolayer cells. I demonstrated DNA fragmentation after incubation with concentrations more than $10{\mu}M$ arsenic trioxide and 100nM taxol for 48h, on the monolayer cells. But the results of HT-29 cell line treated with the combination of taxol and arsenic trioxide was the same as the outcome of control samples that were not treated with any drug. And I don't demonstrated DNA fragmentation on the spheroid cells. These results suggest that apoptosis was not induced in the use of the combination can be thought as that arsenic trioxide might work as an antagonist to inhibit a taxol mechanism to induce apoptosis. And the spheroid cells represented higher resistance against drugs than the monolayer cells.

• Radiation Oncology Journal
• /
• 제7권2호
• /
• pp.149-156
• /
• 1989

HeLa 세포의 spheroid를 배 양시켜 cis-platinum과 carboplatin으로 처리한 후 그 반응을 세포의 생존분획으로 분석하였다. 체외실험 model인 spheroid를 사용하여 platinum유사체의 약효와 방사선 감수성을 평가하고 약제에 대한 단층 세포와 spheroid의 감수성 차이를 세포-생존곡선에서 규명하기 위하여 본 실험을 시행하였다. Cis-platinum 농도-곡선에서 spheroid의 $Cq=3.4{\mu}M$이고 $Co=1.2{\mu}M$이었다. 이 것은 단층세포에 비하여 Co는 큰 변화가 없으나 Cq가 증가되어 cis-platinum이 저산소층 세포보다 활동적으로 분화하는 표면세포에 주로 작용하였으며, 반대로 carboplatin의 효과는 spheroid에 대한 $(Co=15.0{\mu}M)$ 감수성이 단층세포$(Co=32.5{\mu}M)$에 비하여 크게 증가되어, spheroid의 심층 세포에 주로 작용하였다. 방사선과 carboplation의 병용효과를 세포 생존분획이 0.01 수준에서 isobologram으로 분석한 결과 상호작용으로 supra-additive 효과를 나타내었다. 따라서, carboplatin은 cis-platinum에 비하여 신장과 위장에 대한 독성작용이 적고, 방사선과 병용함으로써 향후 더욱 효과적 인 종양 치료에 중요한 역할을 할 것으로 기대한다.

• Biomolecules & Therapeutics
• /
• 제24권3호
• /
• pp.260-267
• /
• 2016

Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.

• 한국고분자학회:학술대회논문집
• /
• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
• /
• pp.266-266
• /
• 2006

The cell spheroid (multicellular mass) is enhanced cell functions because of the cell-cell interaction compared with the individual cell. The objective of this study is synthesis, characterization and evaluation of novel crosslinkers to form spheroid in a short time. Our approach to bridge cells is based on the crosslinking of the cell membrane via the hydrophobic interaction. The crosslinker was prepared by the reaction between ethylenediamine and poly(ethylene glycol) (PEG) derivative with oleyl group as hydrophobic group at the terminal group. The product was characterized with gel permeation chromatography (GPC) and FT-IR. Furthermore, cell culture experiment was also performed to confirm spheroid formation. The function of prepared spheroids was evaluated.