Akon Higuchi is Professor in WIBE as well as Eye Hospital, Wenzhou Medical University. He is a Chair Professor in National Central University (Taiwan) and a visiting professor of King Saud University (Saudi Arabia). He received his B.S. in Tokyo Institute of Technology in 1979, and his Ph.D. in Tokyo Institute of Technology in 1985. He was a Professor and a chair of postgraduate course in Department of Materials & Life Science in Seikei University (Tokyo, Japan) from 1993 to 2007. He received Sofue Memorial Award from Society of Fiber Science, Japan in 1994, and Seikei Academic Award from Seikei Alumni Association in 2003. He is a Fellow of Royal Society of Chemistry (UK), a Fellow of American Institute for Medical and Biological Engineering (AIMBE, USA), Advisory Board of Journal of Materials Chemistry B (Impact factor=4.8, RSC, UK), and Editorial Board of Laboratory Investigation (Impact factor=4.3, Nature). He is an editor of Open Physics and American Journal of Tissue Engineering and stem cell. He is interesting in the development of materials for stem cell research.
(a) Isolation of human adipose-derived stem cells from fat tissue by membrane filtration method
Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, and differentiation ability, depending on the isolation method. We developed an isolation method of hADSCs from a primary fat tissue solution using a membrane filtration method and a membrane migration method. hADSCs where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. hADSCs isolated by the membrane migration method had the highest stem cell surface marker expression and efficient differentiation into osteoblasts. The membrane filtration and migration method will open avenue for the clinical application of hADSC transplantation more easily and with high purity of stem cells.
(b) Development of cell culture materials for expansion and differentiation of human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells
Current xeno-free and chemically defined culture and differentiation methods of hPSCs (human pluripotent stem cells) are not efficient and sometimes not reproducible. Therefore, it is necessary to develop reliable and efficient culture and differentiation methods of hPSCs for future usage in clinical application. We developed a continuous culture method of hPSCs on the dishes immobilized with thermoresponsive nanosegment where a continuous culture method was the first time developed by our group (Prof. Higuchi). We also developed a coating nanosegment materials for hPSC culture in xeno-free culture conditions. Currently, we are developing optimal cell culture materials for hPSC differentiation into cardiomyocyte and retinal pigment epithelium.
(c) Development of cell sorting dishes, which can deplete or concentrate cancer stem cells from tumor
Cancer-initiating cells [cancer stem cells (CSCs)] in colon cancer cells can be selectively suppressed when they are cultured on Pluronic (nanosegment)-grafted dishes, whereas CSCs are maintained on conventional tissue culture dishes and extracellular matrix-coated dishes. CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumorigenic clones. The purification or depletion (suppression) of CSCs should be useful for analyzing CSC characteristics and for clinical application. CSCs can be selectively suppressed from human colon cancer cells containing human adipose-derived stem cells (hADSCs) on Pluronic-grafted dishes (cell sorting dishes), while hADSCs remain on the dishes. hADSCs on Pluronic-grafted dishes after the suppression of the CSCs can differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, and neuronal cells. The CSCs and hADSCs exhibited different characteristics. The selection of hADSCs is possible on Pluronic-grafted dishes that suppressed the CSCs from the fat tissues of cancer patients (i.e., cell-sorting dishes). We are also developing cell sorting dishes for isolation of CSCs.
(d) Preparation of retinal pigment epithelium differentiated from human ES and iPS cells as well as human amniotic fluid stem cells on optimal cell culture biomaterials for treatment of patients with macular degeneration
Current clinical trials that evaluate human pluripotent stem cell (hPSC)-based therapies predominantly target treating macular degeneration of the eyes because the eye is an isolated tissue and generates a low immunoreaction in nature. Retinal pigment epithelium (RPE) differentiated from hPSCs is typically used in most clinical trials for treating patients, whereas bone marrow mononuclear cells (BMNCs) or mesenchymal stem cells (MSCs) are intravitreally transplanted, undifferentiated, into patient eyes. We are now developing efficient differentiation method of hPSC-derived RPE and RPE differentiated from human amniotic fluid stem cells, which were cultured on optimal cell culture biomaterials for future cilinical application of RPE transplantation into patients having macular degeneration.
1994 Sofue Memorial Award, Society of Fiber Science, Japan
2003 Seikei Academic Award, Seikei Alumni Association, Japan
2011-present Council of Chemical Society of Japan, Division of Polymer Science
2013-present Editor in Chief of American Journal of Tissue Engineering & Stem Cell (Columbia International Publishing, USA)
2014-present Advisory Board of Journal of Materials Chemistry B (Royal Society of Chemistry, Impact factor=4.8)
2014-present Fellow, Royal Society of Chemistry (England)
2015-present Fellow, Taiwan Chemical Engineering Society (Taiwan)
2015-present Editor, Open Physics (Walter de Gruyter, German, Impact factor=0.8)
2016 Award of Royal Society of Chemistry, Symposium 2016 of The Japanese Society for Biomaterials (Fukuoka, Japan)
2017-present Editorial Board Member of Laboratory Investigation (Nature, Impact factor=4.3)
2017-present Editor in Chief, Progress in Bioscience and Bioengineering (USA)
2018-present Fellow, American Institute of Medical & Bioengineering (AIMBE, USA)
2018-present The Asia-Pacific (AP) Council of the Tissue Engineering and Regenerative Medicine International Society (TERMIS-AP)
1)A. Higuchi,*, et al., Stem Cell Therapies for Reversing Vision Los, Trends in Biotechnology, 35, Issue 11, 1102–1117 (2017).
2)A. Higuchi*, et al., Polymeric design of cell culture materials that guide the differentiation of human pluripotent stem cells, Prog. Polym. Sci., 65 (2017) 83-126.
3)Peng IC, Higuchi A,* et al., Continuous harvest of stem cells via partial detachment from thermoresponsive nanobrush surfaces, Biomaterials, 76 (2016) 76-86.
4)A. Higuchi*, et al., External stimulus-responsive biomaterials designed for the culture and differentiation of ES, iPS, and adult stem cells, Prog Polym. Sci., 39 (2014) 1585-1613.
5)D.-C. Chen, A. Higuchi*, et al., Purification of human adipose-derived stem cells from fat tissues using PLGA/silk screen hybrid membranes, Biomaterials, 35 (2014) 4278-4287.
6)A. Higuchi*, et al., Design of polymeric materials for culturing human pluripotent stem cells: Progress toward feeder-free and xeno-free culturing, Prog. Polym. Sci., 39(7) (2014) 1348-1374.
7)A. Higuchi*, et al., Physical cues of biomaterials guide stem cell differentiation fate, Chemical Reviews, 113 (2013) 3297-3328.
52.6> Highly Cited Paper
8)A. Higuchi*, et al., Biomimetic Cell Culture Proteins as Extracellular Matrices for Stem Cell Differentiation, Chemical Reviews, 112 (2012) 4507-4540.
9)A. Higuchi*, et al., Biomaterials for the feeder-free culture of human embryonic stem cells and induced pluripotent stem cells, Chemical Reviews, 111 (2011) 3021-3034.
Patents (5-6 items)
1. A. Higuchi, T. Kao, Cell culture article and methods for manufacturing thereof, USP 9,902,941 (February 27, 2018)
2. A. Higuchi, T. Kao, Cell culture article and methods for manufacturing thereof, Japan Patent JP 5944931 (June 3, 2016)
3. A. Higuchi, et al., Methods and systems for isolating, ex vivo expanding and harvesting hematopoietic stem cells, JP 5431786 (December 13, 2013)
4. Akon Higuchi, Nucleotide-transition metal complex catalyst, Japan Patent, JP 5256026 (2013, April 26)
5. A. Higuchi, et al., Methods and systems for isolating, ex vivo expanding and harvesting hematopoietic stem cells, Taiwan patent I 372180 (September 11, 2012)
6. Y. Chang, A. Higuchi, et al., Low biofouling filtration membranes and their forming method, USP 8,062,751 B2 (Nov 22, 2011)