Mebiol® Gel Thermoreversible Hydrogel
for 3D Cell Culture, Stem Cell Expansion, And Other Applications

PNIPAAm-PEG; a block co-polymer of poly(N-isopropylacrylamide)
and poly(ethylene glycol)

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Instructions for use with multiwell plates (pdf)
 
 
 

Muco-Epidermoid Carcinoma
Spheroid formed in Mebiol Gel
 
 
 
 

Use Membiol Gel In flasks or multiwell plates.

Hydrogels are a diverse class of polymeric materials characterized by their network-like structure and high water content. Hydrogels of many kinds have found a wide variety of applications in medicine and life science research weighted towards, but not at all limited to three-dimensional cell culture, tissue engineering, and drug delivery. Properties highly favorable to cell culture and tissue engineering applications prompted the commercialization of Mebiol Gel, a copolymer of poly(N-isopropylacrylamide) and poly(ethylene glycol) (PNIPAAm-PEG) for research purposes in the early 2000's.

Mebiol Gel's defining feature, in contrast to other commercially available hydrogels, is its temperature reversible sol-gel transition. When cooled, Mebiol Gel is a sol (handles like a liquid) but becomes a rigid hydrogel at higher temperatures. In practice, this means extremely easy cell handling. Cultures are seeded into cooled Mebiol Gel and recovered conveniently by cooling the culture vessel and centrifugation.

In the gel state, the highly lipophylic environment of the Mebiol Gel presents an efficient niche for cell proliferation, cell communication, gas and mass exchange, and protection of cells and tissue from shear forces.

Mebiol Gel Features
A liquid (sol) when cooled. A gel at culture temperature.
Easy cell and tissue recovery.
Non-toxic, biocompatible
100% synthetic, pathogen free
High transparency for cell observation
Proven performance

Mebiol Gel published applications include:
Stem cell and pluripotent stem cell culture, expansion, and differentiation
Spheroid culture
Cell implantation
Organ and Tissue Regeneration
Drug Delivery
Non-cell culture application

NEW CITATION - Human Gliobastoma Tumor Initiating Cell Expansion
Li Q, Lin H, Wang O, Qiu X, Kidambi S, Deleyrolle LP, Reynolds BA, Lei Y., Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels.
Sci Rep. 2016 Aug 23;6:31915. doi: 10.1038/srep31915., PMID: 27549983


NEW CITATION - Human Embryonic Stem Cell (hESC) Expansion
Lei Y, Schaffer DV., A fully defined and scalable 3D culture system for human pluripotent stem cell expansion and differentiation. Proc Natl Acad Sci U S A. (2013) Dec 24;110(52):E5039-48.

NEW APPLICATION - Protein Crystallization
see Sugiyama, et al., Cryst. Growth Des., 2013, 13 (5), pp 1899–1904

See the list of Mebiol Gel literature citations that we are aware of below. If you know others that belong on this list, we'd be grateful if you'd forward them along).

     
picture
A gel at 37° C.   A sol at 15° C.

Mebiol Gel comes packaged as a dry powder in in sterile cluture flasks.
Great Matrix for you Matrix Needs   Recover cells and tissue
easily by cold centrifugation
     

Mebiol® Gel Application Examples
1) Culture of primary cancer cells in Mebiol Gel
Selective growth of only primary cancer cells from human cancerous tissue in Mebiol Gel (courtesy Dr. S. Kubota, Dept. of General Surgery, St. Marianna University School of Medicine). This technology enables the characterization of patient-derived primary cancer cells and therefore enabling the evaluation of primary cells for chemosensitivity, malignancy, metastasis activity and other parameters that might influence patient therapy.
   
Human colon cancerous tissue was cultured in Mebiol Gel for 10 days.Only primary cancer cells proliferate from the tissue in Mebiol Gel. Fibroblasts growth in Mebiol Gel is suppresed whereas In collagen and many other 3D gel culture matrices, fibroblasts overgrow and prevent proliferation of primary cancer cells.
   

 

2) Stem Cell Culture

   
3D culture of undifferentiated mouse and Macaca ES cells cultured without LIF or feeder layer cells performed in collaboration with with Dr. K. Hishikawa, Dept. of Clinical Renal Regeneration, University of Tokyo

2D culture on feeder cells

3D culture in Mebiol Gel (day 7)

 
The strong positive alkaline phosphatase staining of Macaca (primate) ES cells cultured in Mebiol Gel suggests undifferentiation.

2D culture on feeder cells

3D Culture in Mebiol Gel (without LIF, day 5)

 
The strong positive alkaline phosphatase staining of Mouse ES cells cultured in Mebiol Gel suggests undifferentiation.
   

 

Mebiol® Gel Ordering Information      
  Product Name Qty Catalog Number
(click for pdf datasheet))
USA Price
($ USD)
  Mebiol®  Gel 1 x 10 ml MBG-PMW20-1001 $331
  Mebiol® Gel 5 x 10 ml MBG-PMW20-1005 $1104
  Mebiol® Gel 10 x 10 ml MBG-PMW20-1010 $2205
  Mebiol® Gel 20 x 10 ml MBG-PMW20-1020 $3307
  Mebiol® Gel 30 x 10 ml MBG-PMW20-1030 $4883
  Mebiol® Gel 40 x 10 ml MBG-PMW20-1040 $6427
  Mebiol® Gel 50 x 10 ml MBG-PMW20-1050 $7903
  Mebiol® Gel 1 x 50 ml MBG-PMW20-5001 discontinued
  Mebiol® Gel 5 x 50 ml MBG-PMW20-5005 discontinued
Mebiol® Gel 20 x 50 ml MBG-PMW20-5020 discontinued

 

Mebiol® Gel Literature Citations and References

Cell Culture and Tissue Regeneration

Stem Cells (human pluipotent stem cell (hPSC) line expansion and differentiation)
A fully defined and scalable 3D culture system for human pluripotent stem cell expansion and differentiation.
Lei Y, Schaffer DV.
Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):E5039-48. doi: 10.1073/pnas.1309408110. Epub 2013 Nov 18.PMID: 24248365

Stem Cells (corneal limbal), review
Towards the use of hydrogels in the treatment of limbal stem cell deficiency
Bernice Wright, Shengli Mi, Che J. Connon
Drug Discovery Today, Volume 18, Issues 1–2, January 2013, Pages 79-86 a
PMID: 22846850

Cell Culture (kidney cyst formation)
Mxi1 influences cyst formation in three-dimensional cell culture.
YJ Yook, KH Yoo, SA Song, MJ Seo, JY Ko, BH Kim, EJ Lee, E Chang, YM Woo, and JH Park
BMB Rep, Mar 2012; 45(3): 189-93.
PMID: 22449707

ROS Cell-Based Assay
Determination of Chronic Inflammatory States in Cancer Patients Using Assay of Reactive Oxygen Species Production by Neutrophils
Yoko Suzuki, Satoshi Ohno, Ryuji Okuyama, Atsushi Aruga, Masakazu Yamamoto, Shigeki Miura, Hiroshi Yoshioka, Yuichi Mori, And Katsuhiko Suzuki
Anticancer Res, Feb 2012; 32: 565 - 570.
PMID: 22287746

ROS Cell-Based Assay
Effect of Green Tea Extract on Reactive Oxygen Species Produced by Neutrophils from Cancer Patients
Katsuhiko Suzuki, Satoshi Ohno, Yoko Suzuki, Yumiko Ohno, Ryuji Okuyama, Atsushi Aruga, Masakazu Yamamoto, Ken-O Ishihara, Tsutomu Nozaki, Shigeki Miura, Hiroshi Yoshioka, And Yuichi Mori
Anticancer Res, Jun 2012; 32: 2369 - 2375.
PMID- 22641677

Stem Cell Culture, Regenerative Medicine
Application of a Thermo-Reversible Gelation Polymer, Mebiol Gel, for Stem Cell Culture and Regenerative Medicine
Kataoka K and Huh N*
2010 Vol. 6 (1): p10-14 (2010)
full text online
http://www.pubstemcell.com/monthly/006010200003.htm

Organ Culture
FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation.
Hiramatsu R, Harikae K, Tsunekawa N, Kurohmaru M, Matsuo I, Kanai Y.
Development. 2010 Jan;137(2):303-12. doi: 10.1242/dev.040519.
PMID: 20040496

Stem Cells (corneal limbal)
Ex vivo cultivation of corneal limbal epithelial cells in a thermoreversible polymer (Mebiol Gel) and their transplantation in rabbits: an animal model.
G Sitalakshmi, B Sudha, HN Madhavan, S Vinay, S Krishnakumar, Y Mori, H Yoshioka, and S Abraham
Tissue Eng Part A, Feb 2009; 15(2): 407-15.
PMID: 18724830

Stem Cell (corneal limbal)
Limbal Stem Cells: Application in Ocular Biomedicine Review Article
Geeta K. Vemuganti, Anees Fatima, Soundarya Lakshmi Madhira, Surendra Basti, Virender S. Sangwan
International Review of Cell and Molecular Biology, Volume 275, 2009, Pages 133-181
PMID: 19491055

Virus infection/replication system
3D cultured immortalized human hepatocytes useful to develop drugs for blood-borne HCV
Hussein Hassan Aly, Kunitada Shimotohno, Makoto Hijikata
Biochemical and Biophysical Research Communications, Volume 379, Issue 2, 6 February 2009, Pages 330-334
PMID: 19103167

Embryo Explant Culture
Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo.
Yamamoto M, Beppu H, Takaoka K, Meno C, Li E, Miyazono K, Hamada H.
J Cell Biol. 2009 Jan 26;184(2):323-34. doi: 10.1083/jcb.200808044. Epub 2009 Jan 19.
PMID:19153222

Hepatocyte Transplantation
Intraperitoneal Transplantation Of Hepatocytes Embedded In Thermoreversible Gelation Polymer (Mebiol Gel) In Acute Liver Failure Rat Model
N. Parveen, A.A. Khan, S. Baskar, M.A. Habeeb, P. Ravindra Babu, A. Samuel, Y. Hiroshi, M. Yuichi, C.M. Habibullah
Journal of Hepatology, Volume 48, Supplement 2, 2008, Page S71
http://hepatmon.com/?page=article&article_id=529

Stem Cells (mesenchymal)
Chrondrogenic differentiation of human mesenchymal stem cells from umbilical cord blood in chemicially synthesized thermoreversible polymer.
Kao, I, et al.
Chinese J. Physiology, 51(4), 252-258 (2008)

Hepatocyte Culture
Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes
Hussein H. Aly, Koichi Watashi, Makoto Hijikata, Hiroyasu Kaneko, Yasutugu Takada, Hiroto Egawa, Shinji Uemoto, Kunitada Shimotohno
Journal of Hepatology, Volume 46, Issue 1, January 2007, Pages 26-36
PMID: 17112629

Stem Cell (Corneal Limbal)
Cultivation of human corneal limbal stem cells in Mebiol gel--A thermo-reversible gelation polymer.
B Sudha, HN Madhavan, G Sitalakshmi, J Malathi, S Krishnakumar, Y Mori, H Yoshioka, and S Abraham
Indian J Med Res, Dec 2006; 124(6): 655-64.
PMID: 17287553

Tissue Engineering (Bone)
In vitro culture of chondrocytes in a novel thermoreversible gelation polymer scaffold containing growth factors.
Yasuda A, Kojima K, Tinsley KW, Yoshioka H, Mori Y, Vacanti CA.
Tissue Eng. 2006 May;12(5):1237-45.
PMID: 16771637

Stem Cells (epithelial)
Isolation of epithelial stem cells from dermis by a three-dimensional culture system.
Medina RJ, Kataoka K, Takaishi M, Miyazaki M, Huh NH.
J Cell Biochem. 2006 May 1;98(1):174-84.
PMID: 16408300

Stem Cells (Corneal Limbal)
Comparative Study on Growth Characteristics of Cadaveric Human Corneal Limbal Stem Cells in Mebiol Gel (a Synthetic Polymer) and on Human Amniotic Membrane. H.N. Madhavan, B. Sudha1, G. Sitalakshmi, S. KrishnaKumar, Y. Mori, H. Yoshioka and S. Abraham.
Invest Ophthalmol Vis Sci 2006;47: E-Abstract 3033. 3033—B186

Tissue Regeneration (Liver)
Thermoreversible gelation polym
er induces the emergence of hepatic stem cells in the partially injured rat liver.
Nagaya M, Kubota S, Suzuki N, Akashi K, Mitaka T.
Hepatology. 2006 May;43(5):1053-62.
PMID: 16628635

Virus Reproduction and Drug Screening
Production of infectious hepatitis C virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral RNA of genotype 1b.
Murakami K, Ishii K, Ishihara Y, Yoshizaki S, Tanaka K, Gotoh Y, Aizaki H, Kohara M, Yoshioka H, Mori Y, Manabe N, Shoji I, Sata T, Bartenschlager R, Matsuura Y, Miyamura T, Suzuki T.
Virology. 2006 Aug 1;351(2):381-92. Epub 2006 May 6.
PMID: 16678876

Embryo Culture
Canonical Wnt Signaling and Its Antagonist Regulate Anterior-Posterior Axis Polarization by Guiding Cell Migration in Mouse Visceral Endoderm.
Chiharu Kimura-Yoshida, Hiroshi Nakano, Daiji Okamura, Kazuki Nakao, Shigenobu Yonemura, Jose A. Belo, Shinichi Aizawa, Yasuhisa Matsui, Isao Matsuo
Developmental Cell, Volume 9, Issue 5, November 2005, Pages 639-650
PMID: 16256739

Evalulation of Cell Line Growth in Mebiol Gel
H.N. Madhavan, J. Malathi, Patricia Rinku Joseph, Mori Yuichi, Samuel JK Abraham and Hiroshi Yoshioka. A study on the growth of continuous culture cell lines embedded in Mebiol Gel., Current Science, 87(9), 1275~77(2004). pdf

Stem Cell Culture and Differentiation
Gene expression profile of human mesenchymal stem cells during osteogenesis in three-dimensional thermoreversible gelation polymer.
Hishikawa K, Miura S, Marumo T, Yoshioka H, Mori Y, Takato T, Fujita T.
Biochem Biophys Res Commun. 2004 May 14;317(4):1103-7.
PMID: 15094382

Liver Regeneration
Evaluation of Thermoreversible gelation polymer for Regeneration of Focal Liver Injury.
M. Nagaya, S. Kubota, N. Suzuki, M. Tadakoro, K. Akashi.
Eur Surg Res, 36:95-103 (2004).
PMID: 15007262

Spheroid Culture (Cancer)
S. Tsukikawa, H. Matsuoka, Y. Kurahashi, Y. Konno, K. Satoh, R. Satoh, A. Isogai, K. Kimura, Y. Watanabe, S. Nakano, J. Hayashi, and S. Kubota.
A new method to prepare multicellular spheroids in cancer cell lines using a thermo-reversible gelation polymer, Artifcial Organs, 27(7), 598 -604(2003).
PMID: 12823414

Wound healing
Wound Dressing of Newly Developed Thermo gelling Thermo reversible Hydro gel.
H. Yoshioka, Y. Mori, S. Kubota ,
Jpn J Artif Organs, 27(2), 503 -506 (1998).
(Japanese Publication- Abstract in English) pdf

Islet Transplantation
In Vitro Studies on a New Method for Islet Micro encapsulation Using a Thermo reversible Gelation Polymer, N-Isopropylacrylamide-Based Copolymer.
S. Shimizu, M. Yamazaki, S. Kubota, T. Ozasa, H. Moriya, K. Kobayashi, M. Mikami, Y. Mori and S. Yamaguchi.
Artif Organs, Vol. 20, No.11 (1996).
PMID: 8908335


Mebiol® Gel Non-Cell Culture Applications

Protein Crystallization Scaffold
see Sugiyama, et al., Cryst. Growth Des., 2013, 13 (5), pp 1899–1904

Scaffold for DNA Electrophoresis and Recovery
Separation and recovery of DNA fragments by electrophoresis through a thermoreversible hydrogel composed of poly(ethylene oxide) and poly(propylene oxide).
Yoshioka H, Mori Y, Shimizu M.
Anal Biochem. 2003 Dec 15;323(2):218-23.
PMID: 14656528

Cell sorting switch
On-Chip Cell Sorting System Using Laser-Induced Heating of a Thermoreversible Gelation Polymer to Control Flow
Y. Shirasaki, J. Tanaka, H. Makazu, K. Tashiro, S. Shoji, S. Tsukita, T. Funatsu.
Anal. Chem., 78, 695-701 (2006)
PMID: 16448041

Cell sorting switch
On-chip cell sorting system using laser-induced heating of a thermoreversible gelation polymer to control flow.
Anal Chem. 2006 Feb 1;78(3):695-701.
Shirasaki Y, Tanaka J, Makazu H, Tashiro K, Shoji S, Tsukita S, Funatsu T.
PMID: 16448041

Cell sorting switch
Microfluidic cell sorter with flow switching triggered by a sol–gel transition of a thermo-reversible gelation polymer.
Kazuto Ozaki, Hirokazu Sugino, Yoshitaka Shirasaki, Tokihiko Aoki, Takahiro Arakawa, Takashi Funatsu, Shuichi Shoji
Sensors and Actuators B: Chemical, Volume 150, Issue 1, 21 September 2010, Pages 449-455
http://www.sciencedirect.com/science/article/pii/S0925400510006143

DNA molecular Sorting
Microfluidic active sorting of DNA molecules labeled with single quantum dots using flow switching by a hydrogel sol–gel transition
Mai Haneoka, Yoshitaka Shirasaki, Hirokazu Sugino, Tokihiko Aoki, Takahiro Arakawa, Kazuto Ozaki, Dong Hyun Yoon, Noriyuki Ishii, Ryo Iizuka, Shuichi Shoji, Takashi Funatsu
Sensors and Actuators B: Chemical, Volume 159, Issue 1, 28 November 2011, Pages 314-320
http://www.sciencedirect.com/science/article/pii/S0925400511005521

Drug delivery
J Neurooncol. 2006 Mar;77(1):9-15.
Novel drug delivery system using thermoreversible gelation polymer for malignant glioma.
Arai T, Joki T, Akiyama M, Agawa M, Mori Y, Yoshioka H, Abe T.
J Neurooncol. 2006 Mar;77(1):9-15.
PMID: 16292493

Drug delivery
Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes.
Arai T, Benny O, Joki T, Menon LG, Machluf M, Abe T, Carroll RS, Black PM.
Anticancer Res. 2010 Apr;30(4):1057-64.
PMID: 20530409

Cell Culture for drug screening
Alternatives to Animal Testing and Experimentation
Wakui et al. in vitro Thermoreversible Gel Disc Quantitative Assay of Rat Angiogenesis.
AATEX 16(2), 59-65, 2011
https://www.jstage.jst.go.jp/article/aatex/16/2/16_2_59/_pdf

Mebiol® Gel Physical Properties

Physical Properties
A synthetic hydrogel with thermoreversible gelation. II. : Effect of added salts.
H. Yoshioka, M. Mikami, Y. Mori, and E. Tsuchida.
J. Macromol. Sci., A31(1), 121-125 (1994).
http://www.tandfonline.com/doi/abs/10.1080/10601329409349723#.UvFzqtKE1NQ

Physical Properties
Thermoreversible gelation on heating and on cooling of an aqueous gelatin-poly(N-isopropylacrylamide) conjugate. ,
H. Yoshioka, Y. Mori, S. Tsukikawa, and S. Kubota,
Polym. Adv. Tech., 9, 155-158 (1998).
http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-1581(199802)9:2%3C155::AID-PAT750%3E3.0.CO;2-G/abstract

Physical Properties
A Synthetic hydrogel with thermoreversible gelation. I. Preparation and rheological properties , H. Yoshioka, M. Mikami and Y. Mori.
J.M.S- Pure Appl. Chem., A31(1), pp. 113-120 (1994).
http://www.tandfonline.com/doi/abs/10.1080/10601329409349722#.UvFK1dKE1NQ

Physical Properties
Preparation of Poly (N-Isopropylacrylamide)-b-Poly(Ethylene Glycol) and Calorimetric Analysis of its Aqueous Solution ,
H. Yoshioka, M. Mikami and Y. Mori,
J.M.S- Pure Appl. Chem., A31(1), pp. 109-112 (1994).
http://www.tandfonline.com/doi/abs/10.1080/10601329409349721#.UvFLB9KE1NQ

Physical Properties
A synthetic hydrogel with thermoreversible gelation. III. : An NMR study of the Sol-Gel transition.
H. Yoshioka, Y. Mori and James A. Cushman.
Polym. Adv. Tech., 5, pp. 122-127 (1994).
http://onlinelibrary.wiley.com/doi/10.1002/pat.1994.220050207/abstract


 

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