The Future of Transplantation

Toward the future of organ transplantation and
regeneration medicine using bioengineered medical-grade porcine organs.

Our mission

Our goal is to provide transplantable organs, tissues, and cells to patients
with organ failure or intractable diseases.

What is a medical-grade pig?

We generated designated pathogen-free (DPF) pigs with enhanced functions
using cutting-edge bioengineering technologies, including somatic cell cloning.

About us

PorMedTec Co. Ltd. was established in February 2017 based on research outcomes of the Meiji University International Institute for Bio-Resource Research (MUIIBR) led by Professor Hiroshi Nagashima. MUIIBR is a globally leading group in animal bioengineering, including the production of cloned pigs, generation of pig models for human genetic diseases, organ regeneration using blastocyst complementation, and cryopreservation of embryos and organoids.

In 2021, we established our new mission: to provide transplantable organs, tissues, and cells for the treatment of patients with organ failure or intractable diseases, thereby contributing to global medical care and human health. To achieve this goal in the fastest way, we explored an innovative business using bioengineered medical-grade pigs as hosts to manufacture cost-competitive products with a reliable and stable supply.

Unmet medical needs to be addressed

Only 2% of patients on the waiting list with end-stage organ failure can undergo transplantation therapy in Japan due to the lack of organ donors. Organ shortage is also a serious issue in the United States; 17 people die every day while waiting for a transplant.

Current treatments, such as dialysis, burden patients and their families and generally result in a decreased quality of life (QOL). Furthermore, the medical costs are enormous: in Japan, 2 trillion yen is spent annually on renal dialysis, constituting 4% of the total medical expenditure of the country.

2

%

Organ transplantation performed / Patients on the waiting list

17

People/Day

Number of deaths per day among waiting patients

4

%

Economic burden of dialysis on the national medical expenditure in Japan

Patients on the waiting list vs. Transplants Performed
(2020)

Source: Organdonor.gov　

PorMedTec’s unique core technologies will provide patients with innovative new therapies that are urgently needed.

Core Competencies

Leading bioengineering technologies for genetic engineering and cloning of pigs
High-quality manufacturing of transplantable organs/tissues/cells using medical-grade designated pathogen-free (DPF) pigs produced by an original low-cost U-iR system
Production of humanized organs using the DPF pigs and human pluripotent stem cells
Core Business

We are developing human-compatible organs, tissues, and cells using our platform technologies by genetically engineering pigs. Our unique production system for medical-grade DPF pigs facilitates domestic and global business development in a cost-competitive manner.

Mission Statement

Our mission is to fulfill the increasing demand for transplantable organs, improve the quality of life for patients and their families, and reduce the economic burden associated with transplantation medicine.

Platform Technology
#1

Generation of genetically engineered pigs

PorMedTec's genetic bioengineering platform includes genetic modifications of porcine somatic and embryonic cells. We also make full use of our sophisticated artificial reproductive technologies, including somatic cell cloning, in vitro oocyte maturation and fertilization, ICSI-mediated gene transfer, embryo cryopreservation, blastocyst complementation, and fetal surgery, to create and propagate pigs with improved traits for medical use.

Platform Technology

#2

Medical-grade designated pathogen-free (DPF) pigs

We developed a unique U-iR (Uterectomy isolated rearing) system to produce DPF pigs that satisfies the hygienic standards for xenotransplantation.

In 2021, we started a five-year project on the development of a DPF pig production/ application facility with the support of the Japan Agency for Medical Research and Development.

Platform Technology

#3

Development of humanized organs

Using the conceptus organ niche complementation method in pigs, we created genetically engineered porcine organ composed of human induced pluripotent stem (iPS) cells and porcine fetal anlagens. The pig-derived cells in the hybrid anlagen are genetically engineered to be eliminated after transplantation into human patients; the graft then grows in the patient as a humanized organ.

Publications

PorMedTec was established as a spin-off venture at the Meiji University International Institute for Bio-Resource Research (MUIIBR). The comprehensive partnership agreement between PorMedTec and Meiji University allows us to utilize all the research outcomes of the MUIIBR.

Please refer to the following URL to access the publications of MUIIBR

Diabetes model pig

Umeyama K, Watanabe M, Saito H, Kurome M, Tohi S, Matsunari H, Miki H, Nagashima H: Dominant t-negative mutant hepatocyte nuclear factor 1alpha induces diabetes in transgenic-cloned pigs. Transgenic Research, 18(5): 697-706, 2009.

Umeyama K, Nakajima M, Yokoo T, Nagaya M, Nagashima H: Diabetic phenotype of transgenic pigs introduced by dominant-negative mutant hepatocyte nuclear factor 1α. Journal of Diabetes and its Complications, 31(5):796-803, 2017.

Immunodeficient pig

Watanabe M, Nakano K, Matsunari H, Matsuda T, Maehara M, Kanai T, Kobayashi M, Matsumura Y, Sakai R, Kuramoto M, Hayashida G, Asano Y, Takayanagi S, Arai Y, Umeyama K, Nagaya M, Hanazono Y, Nagashima H: Generation of interleukin-2 receptor gamma gene knockout pigs from somatic cells genetically modified by zinc finger nuclease-encoding mRNA. PLOS ONE 8:e76478, 2013.

Pancreatogenesis-disabled pig

Matsunari H, Nagashima H, Watanabe M, Umeyama K, Nakano K, Nagaya M, Kobayashi T, Yamaguchi T, Sumazaki R, Herzenberg L.A., Nakauchi H. Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs. Proc Natl Acad Sci USA, 110:4557-4562, 2013.

Renal agenesis pig

Matsunari H, Watanabe M, Hasegawa K, Uchikura A, Nakano K, Umeyama K, Masaki H, Hamanaka S, Yamaguchi T, Nagaya M, Nishinakamura R, Nakauchi H, Nagashima H: Compensation of disabled organogeneses in genetically modified pig fetuses by blastocyst complementation. Stem Cell Reports:14:21-33, 2020.

Hepatogenesis-disabled pig

Matsunari H, Watanabe M, Hasegawa K, Uchikura A, Nakano K, Umeyama K, Masaki H, Hamanaka S, Yamaguchi T, Nagaya M, Nishinakamura R, Nakauchi H, Nagashima H: Compensation of disabled organogeneses in genetically modified pig fetuses by blastocyst complementation. Stem Cell Reports:14:21-33, 2020.

Pigs Lacking Pancreatic β-cells

Nagaya M, Hasegawa K, Watanabe M, Nakano K, Okamoto K, Yamada T, Uchikura A, Osafune K, Yokota H, Nagaoka T, Matsunari H, Umeyama K, Kobayashi E, Nakauchi H, Nagashima H: Genetically engineered pigs manifesting pancreatic agenesis with severe diabetes. BMJ Open Diabetes Research & Care, 8:e001792, 2020.

Marfan syndrome model pig

Umeyama K, Watanabe K, Watanabe M, Horiuchi K, Nakano K, Kitashiro M, Matsunari H, Kimura T, Arima Y, Sampetrean O, Nagaya M, Saito M, Saya H, Kosaki K, Nagashima H, Matsumoto M: Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts. Scientific Reports, 6:24413, 2016.

Dilated cardiomyopathy model pig

Matsunari H, Honda M, Watanabe M, Fukushima S, Suzuki K, Miyagawa S, Nakano K, Umeyama K, Uchikura A, Okamoto K, Nagaya M, Toyooka T, Sawa Y, Nagashima H: Pigs with δ-sarcoglycan deficiency exhibit traits of genetic cardiomyopathy. Laboratory Investigation, 100:887-899, 2020.

Compensation of lethal traits by blastocyst complementation

Matsunari H, Watanabe M, Nakano K, Enosawa S, Umeyama K, Uchikura A, Yashima S, Fukuda T, Klymiuk N, Kurome M, Kessler B, Wuensch A, Zakhartchenko V, Wolf E, Hanazono Y, Nagaya M, Umezawa A, Nakauchi H, Nagashima H: Modeling lethal X-linked genetic disorders in pigs with ensured fertility. Proc of Natl Acad Sci USA, 115:708-713, 2018.

R&D pipelines

R&D pipelines

Islet xenotransplantation

First-generation islet xenotransplantation

The target of first-generation islet xenotransplantation is to prevent severe hypoglycemia in hypoglycemia-unaware patients. We supply first-generation xeno-islet products prepared from the pancreas of wild-type DPF pigs. The islets are encapsulated in alginate microcapsules to protect against immune rejection. These are transplanted subcutaneously using an implantable device.

Next-generation islet xenotransplantation

We are currently developing genetically engineered pigs with improved insulin secretion and anti-apoptotic abilities. We are working to deliver a higher QOL to patients, including relief from insulin dependence and consequently, the elimination of daily insulin injections.

R&D pipelines

Transplantation therapy with humanized kidneys

Curing patients with end-stage renal failure is one of our goals. We are developing humanized kidneys composed of genetically engineered porcine kidney anlagens and human iPS cell-derived renal progenitor cells.

R&D pipelines
Xenotransplantation

The first successful human heart transplantation from a genetically engineered pig occurred on January 7, 2022. This will encourage the clinical application of xenotransplantation for various organs. Kidney xenotransplantation is expected to serve as a cure for numerous patients waiting for kidney transplantation. We are developing DPF pigs with multiple genetic modifications that allow for kidney xenotransplantation.

BBC News
Technical consulting service

Cryopreservation technology

Based on our extensive knowledge on and experience in embryo vitrification, we have developed a unique vitrification technique applicable for the cryopreservation of a variety of subjects, including fetal anlagens, pancreatic islets, organoids, and artificial tissues such as cell sheets. We can provide an optimized cryopreservation protocol for the specific materials of interest.

Pancreatic Islets

Nagaya M, Matsunari H, Kanai T, Maehara M, Nakano K, Umeki I, Katsumata Y, Kasai Y, Sakai R, Kobayashi M, Honda K, Abe N, Watanabe M, Umeyama K, Nagashima H: An effective new cryopreservation procedure for pancreatic islets using hollow fiber vitrification. Hormone and Metabolic Research, 48(8):540-549, 2016.

Pig Embryonic Kidneys

Matsumoto K, Yokoo T, Matsunari H, Iwai S, Yokote S, Teratani T, Gheisari Y, Tsuji O, Okano H, Utsunomiya Y, Hosoya T, Okano H.J, Nagashima H, Kobayashi E. Xenotransplanted embryonic kidney provides a niche for endogenous mesenchymal stem cell differentiation into erythropoietin-producing tissue. Stem Cells, 30:1228-35, 2012.

Cell Sheets

Maehara M, Sato M, Watanabe M, Matsunari H, Kokubo M, Kanai T, Sato M, Matsumura K, Hyon SH, Yokoyama M, Mochida J, Nagashima H: Development of a novel vitrification method for chondrocyte sheets. BMC Biotechnology, 13:58, 2013.

Technical consulting service

Made-to-order production of genetically engineered pigs

Genetically engineered pigs have been utilized for several purposes, including organ regeneration research (ref 1-3) and validation of a new drug/therapy using model pigs (ref 4). We provide a service that creates genetically engineered and cloned pigs to meet the specific requirements of our clients.

1

T. Rashid, T. Kobayashi, H. Nakauchi: Revisiting the flight of Icarus: making human organs from PSCs with large animal chimeras

2

Cell Stem Cell, 15 (2014), pp. 406-409. Matsunari H, Nagashima H, Watanabe M, Umeyama K, Nakano K, Nagaya M, Kobayashi T, Yamaguchi T, Sumazaki R, Herzenberg L.A., Nakauchi H. Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs. Proc Natl Acad SciUSA, 110:4557-62. 2013.

3

Yokote S, Matsunari H, Iwai S, Yamanaka S, Uchikura A, Fujimoto E, Matsumoto K, Nagashima H, Kobayashi E, Yokoo T: Urine excretion strategy for stem cell-generated embryonic kidneys. Proc Natl Acad Sci USA, 112: 12980-12985, 2015.

4

McGonigle P, Ruggeri B: Animal models of human disease: Challenges in enabling translation. Biochemical Pharmacology, 87: 162-171, 2014.

Corporate
Profile

Address
Meiji University Center of Collaborative Innovation and Incubation, T201
2-3227 Mita, Tama, Kawasaki 214-0034, Japan
Company Background
PorMedTec was founded in February 2017 with the aim of practical implementation of the research outcomes of the Meiji University International Institute for Bio-Resource Research (MUIIBR).
Business Description
Production and sales of:
  • Pancreatic islets for xenotransplantation using genetically engineered pigs
  • Humanized organs for transplantation using genetically engineered pigs
  • Genetically engineered pig organs for xenotransplantation
    • Made-to-order production of genetically engineered pigs
    Technical consulting service for the cryopreservation of biomaterials
    Shareholders
    Eight Roads Ventures & F-Prime Capital (Global VC backed by Fidelity)
    Management Team
    Employees
    As of December 2021, ProMedTec currently employs 10 board directors.

    Management Team

    Hiroshi Nagashima, Ph.D.

    Founder, Chief Scientist

    Professor, Laboratory of Medical Bioengineering, Department of Life Sciences, School of Agriculture, Meiji University
    Director, Meiji University International Institute for Bio-Resource Research

    Prof. Hiroshi Nagashima was awarded a Ph.D. from the University of Tokyo in 1984. He started his career working on the embryology of large domestic animals, mainly pigs and cattle, at the Research Center of Nisshin Flour Milling Co., Ltd., Japan. In 1991 he moved to Australia to work as a visiting research fellow at the Department of Obstetrics and Gynecology, Medical School, University of Adelaide, Australia. After this he accepted a position as a senior research scientist at BresaGen Ltd., Australia, where he engaged in a xenotransplantation project. He returned to Japan in 1997, working for two years at the Division of Organ Transplantation, Biomedical Research Center, Osaka University Medical School, before becoming an associate professor at Meiji University in 1999. His current research focus includes the production of genetically modified pigs as potential organ donors for xenotransplantation, in vivo organ regeneration using genetically engineered pigs, creation of disease models using genome editing and somatic cell cloning technology, and cryopreservation of embryos and artificial tissues.

    Genjiro Miwa, MBA

    Founder, CEO, Board Director

    Founder & Chairman of Megakaryon Corporation, a producer of iPS platelets

    Co-founder and CEO of iCELL, a regenerative medicine patent broker

    Co-founder & director of Ardito Asset Management Co., Ltd., an investment firm

    After working at Bain & Company, he co-founded BioSurface Technology (currently part of Sanofi) which developed cultured skin substitutes.

    Graduated from the University of Tokyo Faculty of Economics
    Graduated from Harvard Business School (MBA with Distinction)

    Council Member of the World Economic Forum (The Davos Agenda)

    Kazu Umeda, M.S.

    Board Director

    Co-founder and Represent Director, SIIF Impact Capital Inc., a JV with SIIF, the leading ecosystem builder of impact investing in Japan.

    Prior Experience
:
    M3 Inc. (TYO: 2413)

    Venture Investment Partner,Business development group
    Co-founder & Representative Director, M3i Inc.

    INCJ Inc.(Japanese Government Fund)
    Vice President

    Japan Asia Investment Co., Ltd. (TYO: 8518)

    Head of CEO’s office, HeadQuarter, Tokyo Japan
    President, JAIC Asia Holdings Pte Ltd, Singapore
    President, PT JAIC Indonesia, Jakarta
    President, JAIC Thailand Co., Ltd, Bangkok
    Investment Manager, JAIC America, Inc., Palo Alto, California, USA

    Membership in professional committee :
    Evaluation committee member of Ministry of Education, Culture, Sports, Science and Technology
    Evaluation committee member of Japan Agency for Medical Research and Development (AMED)

    M.S., Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    B.S., Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    Shin-ichiro Komoto

    Board Director

    Investment & Development Manager for the healthcare sector at Eight Roads, a Japanese VC that manages funds from Fidelity, a major US financial firm.

    At Mitsui & Co., Ltd., where he worked for 18 years, he helped to start new businesses in the IT and healthcare sector and worked on M&A and business management. He lived and worked abroad in the US, Singapore, and Vietnam for nine years.

    Tokyo Metropolitan University (Electric Engineering)
    
INSEAD (Executive Educational Program)

    Hirotada Nagai, M.S.

    Board Director

    Director, Kyoya Corporation (chemical industry pharmaceutical trading company)

    Held various positions within the Ministry of Health, Labour and Welfare, such as the Compliance and Narcotics Division (GMP Advisor) of the Pharmaceutical and Food Safety Bureau, as well as positions in the Research and Development Division (Technical Head Deputy Director) of the Health Policy Bureau.

    Experience gained through secondment to the Office of Medical Devices I of the Pharmaceuticals and Medical Devices Agency (PMDA), and the Health and Medical Team in the Strategic Investment Group of the Innovation Network Corporation of Japan (INCJ).

    Earned Master of Pharmacy from the Gifu Pharmaceutical University Graduate School of Pharmacy.

    Iichiro Amano

    Board Director

    After joining Daiwa Securities, he was engaged in equity sales trading in the Institutional Sales Department. After retiring from Daiwa Securities, he worked as a fund manager and CTO of a investment company, and later worked in corporate management and venture support.

    Graduated from Waseda University, School of Commerce.

    Masahiko Hirata

    Statutory Auditor

    Examiner at Bank Examination Department, Senior Examiner at Financial System and Bank Examination Department, and Kumamoto Branch Manager of the Bank of Japan; Executive Director at Deposit Insurance Corporation of Japan; Senior Director at Sumitomo Mitsui Trust Bank, Limited; Advisor at Mitsui Life Insurance Company, Limited.

    Senior Advisor, YAMADA Consulting Group Co.Ltd. (to present), Senior Advisor, Grant Thornton Taiyo LLC (to present)

    Graduated from Waseda University

    Hidetaka Hara, M.D., Ph.D.

    Scientific Advisor

    Dr. Hara is currently a Professor at the College of Veterinary Medicine, Yunnan Agricultural University, Kunming, Yunnan, China, where he is working in the xenotransplantation program. He is a fully-trained surgeon, including transplantation surgery, and has a Ph.D. in transplant immunology. Dr. Hara worked in the field of xenotransplantation research with Dr. Cooper for more than 17 years, initially at the University of Pittsburgh. He has extensive experience working with large animal models (e.g., pigs and nonhuman primates). He has participated in pig-to-baboon or monkey heart, liver, kidney, islet, and corneal transplantation, as well as in various pig allotransplantation models. In addition, he has extensive experience with immune assays including immune monitoring of the recipient after xenotransplantation and in vitro assays. He has contributed to illuminating how genetic modifications in pigs can protect their organs from human immune responses.

    1995

    Graduated from Kawasaki Medical School, Okayama, Japan (M.D.)

    1996

    Matsuyama Red Cross Hospital (Surgery), Ehime, Japan

    1998

    National Hiroshima Hospital (Surgery), Hiroshima, Japan

    2004

    Graduated from Graduate School of Medical Sciences, Hiroshima University, Hiroshima, Japan (Ph.D.)

    2004

    Postdoctoral research fellow at the Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania, USA

    2007

    Research Instructor of Surgery at the Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania, USA

    2011

    Research Assistant Professor of Surgery at the Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pennsylvania, USA

    2016

    Assistant Professor of Surgery at the University of Alabama at Birmingham, Alabama, USA

    2017

    Associate Professor of Surgery at the University of Alabama at Birmingham, Alabama, USA

    2022

    Associate Professor at the College of Veterinary Medicine, Yunnan Agricultural University, Yunnan, China

    2022

    Professor at the College of Veterinary Medicine, Yunnan Agricultural University, Yunnan, China

    Contact

    For further details on our services or products, please make an inquiry via the contact form.

    Meiji University Center of Collaborative Innovation and Incubation T201, 2-3227 Mita, Tama, Kawasaki 214-0034, Japan

    Contact Form