Future Pharmaceutical Sciences and
Recent Advancement of Medical Sciences
Kunio KAWAMURA, Ph.D.
Otsuka Pharmaceutical Co. Ltd.

Outline of this speech-1
Following two topics will be presented as representatives
Co.
(1) Application of iPS : iPS cells are engineered by introducing specific genes into cells derived from the skin, blood and other body tissues. They have the potential capacity to develop into cells of various parts of the body. The first clinical study has just started to treat age-related macular degeneration, an intractable disease of the eye. iPS cells turn into pigment epithelial cells, and thereafter, are cultivated to multiple applicable sheets for transplants to many patients. The cultivated cell sheets will be a kind of medical device.
The application is now expanding to various medical sciences.

Outline of this speech-2
(2 ) Clinical trials using therapeutic porcine cell implants have already been at the final stage.
Microspheres containing live pig’s islet cells are
implanted into a patient's abdomen. Once implanted, the encapsulated islet cells work by self-regulating and efficiently secreting insulin and glucagon in response to the patient's changing glucose levels. The capsules containing islet cells are protected from the body's immune response by the semi-permeable membrane, and also permit the bidirectional diffusion of molecules essential for cell metabolism and the outward diffusion of waste products.
This technology is now being extended to treat other diseases. Those encapsulated cells will be categorized as combination products

Human Organs/Cells Transplantation
1 ． Shortage of Donors
2 ． Utilization of iPS Cells
1) Use of Human Cells (ex. Conversion from
Human skin cells)
2) Generation of Human Organ in Animal by
Animal-Human Chimeric Embryo Technology
(ex. Human Blood in sheep. Human Heart and/or , spleen in Pig)
3. Make use of Animal Organ by an New Invention to
Eliminate Rejection Reaction ．
Clinical trials are now progressing for 2-1) and 3 . These have need for new concept of pharmaceutical sciences.

Human-Human Heart Transplantation in Japan
Waiting
Transplanted

1. Generation of Human Organ, Tissue and/or Cells from iPS Cells
2. Generation of Human Organ, Tissue and/or Cells in Animal by Elimination
Rejection
3. Making Use of Animal Tissue or Cell, as it is, by Elimination Rejection

Mechanisms of Rejection Reaction
Lymphocytes/Immune cells attack the Transplanted Organ
Lymphocytes/
Immune Cells
Transplanted Organ

In order to Reduce Rejection reactions
There are two methods.
1) One is to use the same kind of biological products. ex. Human – Human transplantation.
2) The second is to make change the differences to harmonize, by make use of genetic technology.
ex. using iPS cells.
3) The third is to protect cells from the rejection reactions by artificial barriers. ex. Protecting cells by blocking higher molecular barrier.

Examples of New Type of
Pharmaceuticals and Medical devices
・Generation Retina sheet for multi-patients,
(under clinical trial)
・Generation of Blood/Blood cells in animals formultipatients,
・Encapsulated Insulin Secreting Pig cells
( under clinical trial)
Pharmaceutical science should cooperate and contribute the completion of these technology, and have to care how to deliver, storage and use.

ES Cell and iPS Cells
Embryonic stem cells are able to develop into any type of cell .
Embryonic stem cells ( ES cells ) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage embryo . Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the embryoblasto or inner cell mass (ICM) results in destruction of the fertilized human embryo, which raises ethical issues.
Induced pluripotent stem cells, abbreviated as iPS cells are a type of pluripotent stem cell artificially derived from a non-pluripotent cell – typically an adult somatic cell – by inducing a "forced" expression of specific genes. Induced pluripotent stem cells are similar to natural pluripotent stem cells, such as embryonic stem (ES) cells, in many aspects. Induced pluripotent cells have been made from adult stomach, liver, skin cells and blood cells.

How to manufacture iPS Cells
Four kinds of genes Skin Cells
Reset
CELLS
Cells
Muscle cells
Nervous Cells
Skin Cells
White Blood Cells Red Blood Cells

Application of iPS Cell Technology to Medical science
The first case of iPS Cell thechnology to medical sciences.
“ Age-Related Macular Degeneration ： iPS Cells-Derived Retinal Pigment Epithelium
Cell”

Medical Treatment of Age-Related
Macular Degeneration for Eye
Patients of Age-Related Macular Degeneration for Eye
Cells
10 months
Skin Cells
Genes into Cell iPS Cells
Macula Cell sheet
Trans Plantation

Age-Related Macular Degeneration
ー iPS Cells-Derived Retinal Pigment Epithelium Cell
Sheey （シートを将来市販する：医療機器） iPS Cells
Cultured
Rtinal Pigment
Epithelium Cell cells are
Transplanted to Retina
Cultured to
Cell sheet
Retinal
Pigment
Epithelium
Cell
Eye lens

Embryo Animal Embryo
Human Cells

Use of Animal Organ –
Xeno-trans-plantation-
1 ． How to Overcome Rejection/
Immune
2 ． Ethics of Life

Human Organ (Pancreas) cultivated in Pig
Human iPS cells
Birth of animal with human pancreas
Fertilized egg
Genetically manipulated Embryo
Injection to animal womb and incubate

Insulin
Nutrition, Oxygen
Anti-Body
Pig Islet Cells
Semi-permeable
Membrane

Cell Encapsulation

Animal Organ from Pig cells to be Transplanted
Get animation: Processing pig cells for transplants

Islets isolated from neonatal porcine pancreas in alginatepolyornithine

Capsules for sale ( Before Use)

Diabetes Treatment Utilizing Implanted
Encapsulated, Insulin-Producing Cells
Would Replace Existing Type 1 Diabetic
Drugs

Kunio KAWAMURA