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BioTime Demonstrates Efficient Method for the Manufacture of Cartilage-Producing Cells from Human Embryonic Stem Cells



  BioTime Demonstrates Efficient Method for the Manufacture of
  Cartilage-Producing Cells from Human Embryonic Stem Cells

 - First demonstration of a scalable source of highly purified and identified
 progenitor cells capable of making definitive (non-hypertrophic) cartilage -

Business Wire

ALAMEDA, Calif. -- April 23, 2012

BioTime, Inc. (NYSE Amex: BTX) and its wholly owned subsidiary OrthoCyte
Corporation reported today a means of manufacturing cartilage from human
embryonic stem cells that is suited for industrial scale-up of a product for
the treatment of osteoarthritis. The paper, published online (ahead of print)
in the peer-reviewed journal Regenerative Medicine, characterizes a progenitor
cell line produced from human embryonic stem (hES) cells using proprietary
ACTCellerate™ technology. The study reports that the cells are capable of
regenerating cartilage with long sought-after identification markers. The
study also shows that the cells can be directly expanded on a scale needed for
industrial manufacture, which will be necessary in order to make
transplantable cells available in commercial quantities.

In today’s publication, BioTime scientists reported on one ACTCellerate™ line
designated 4D20.8. This proprietary cell line is the cellular component of
OrthoCyte’s product in development, OTX-CP07. The scientific publication
demonstrates that 4D20.8 cells possess site-specific markers of craniofacial
mesenchyme, in particular, markers of proximal mandibular mesenchyme. This
tissue is of significance in that it naturally produces one of the strongest
joint cartilages of the body. The study documented conditions in which the
cells can be propagated on a large scale, conditions in which the cells can be
differentiated into cartilage in the laboratory, and evidence that the cells
could repair damage to knee joints in rat models.

Another significant finding reported in the study is that the OrthoCyte 4D20.8
cells lacked certain mesenchymal stem cell (MSC) markers. MSCs have the
ability to proliferate in response to fractures to generate a transient type
of cartilage called “hypertrophic cartilage” that functions as a temporary
repair of the fracture. Over time, that hypertrophic cartilage is transformed
into bone. Therefore, due to their propensity to hypertrophy, MSCs have not
served as an effective source of definitive cartilage for joint repair. When
compared to MSCs in studies published in the current paper, 4D20.8 cells
displayed markers consistent with definitive cartilage progenitors and showed
a marked decrease in the expression of hypertrophic chondrocyte markers.

“We see osteoarthritis as one of the low-hanging fruits in regenerative
medicine,” said Michael D. West, Ph.D., BioTime’s Chief Executive Officer.
“The rapid rise of this market due to the aging of the baby boom population,
the current lack of a cure for the disease, and the ease of scaling our
product have led to our prioritizing this product for development.”

Arnold Caplan, Ph.D., OrthoCyte’s Chief Scientific Officer and Director of the
Skeletal Research Center at Case Western Reserve University, commented, “The
long-stated goal in orthopedic research has been to isolate the progenitors to
specific and diverse types of cartilage in the body, such as those of the ear,
nose, trachea, sternum, and weight-bearing joints. Cloning progenitors derived
from hES cells is a novel method of obtaining these cells, which will be of
great interest to those in the research community and those seeking to cure
the debilitating disease of osteoarthritis.”

A discussion of OrthoCyte’s product development strategy delivered by Dr.
Caplan and comments on the implications of BioTime’s scientific advances are
available online at www.biotimeinc.com and www.orthocyte.com.

Background

The emerging field of regenerative medicine is based on new discoveries in
stem cell biology that, for the first time in medicine, may lead to
technologies with the capacity to manufacture all of the cell types in the
human body. In an era when age-related degenerative disease is the largest
category of unmet medical needs, there is great interest in the potential for
stem cell therapies to lead to treatments. The most common complaint of an
aging population is the degenerative disease known as osteoarthritis. This
painful condition is caused by the degeneration of the cartilage lining the
ends of the bones in the joint. Because human cartilage has no innate
regenerative capacity, and there currently is no cure for the disease, much
attention has been directed at finding a means of introducing
cartilage-forming cells into the aged joint to repair the tissue. An estimated
27 million Americans suffer from the disease, and this number is rapidly
growing with the aging of our population. A safe and effective means of
regenerating functional cartilage cells in human patients could therefore
address a significant market.

Human embryonic stem and induced pluripotent stem (iPS) cells have attracted
attention due to their capacity to generate all body cell types, a
characteristic called “pluripotency.” The adult human body also contains stem
cells called “adult stem cells” that reside in some tissues and can contribute
to the repair of that tissue in the case of injury or disease. Adult stem
cells include the MSCs found in bone; MSCs possess the ability to proliferate
in response to fractures, generating a transient type of hypertrophic
cartilage that functions as temporary fracture repair. However, because
hypertrophic cartilage eventually transforms into bone, MSCs have not served
as an effective source of definitive cartilage for joint repair.

ACTCellerate™ technology is a proprietary method of isolating and expanding
cell lines from hES or iPS cells into human progenitor cell lines in a
purified and primitive state. These human progenitor cell lines, or simply
“ACTCellerate™ lines”, may solve certain technological issues associated with
the manufacture of products from hES or iPS cells, in particular, methods for
the generation of large quantities of highly identified and purified cell
types. This is critical in the case of cell replacement therapies. Human
therapeutic products require a high degree of purity to meet the hurdles of
regulatory approval and acceptance in medical practice. BioTime scientists
have identified embryonic progenitors to diverse types of human cartilage that
show a high degree of purity, known identity, and scalability. The 4D20.8 cell
line provide for the first time a means of manufacturing cells that
subsequently generate numerous types of other cells, which will potentially
address large unmet needs in orthopedic medicine and be useful in multiple
applications that have not to date been addressed through the use of
adult-derived stem cells.

About OrthoCyte Corporation

OrthoCyte Corporation (OrthoCyte), www.orthocyte.com, a subsidiary of BioTime,
Inc., is a biotechnology company developing cell-based therapies for
orthopedic disease. The company’s lead product is OTX-CP07, monoclonal human
embryonic progenitor cells lines for the repair of osteoarthritis. In
addition, OrthoCyte has proprietary hES-derived progenitors to skeletal
muscle, tendon, and bone, all in the preclinical phases of development.

About BioTime, Inc.

BioTime, headquartered in Alameda, California, is a biotechnology company
focused on regenerative medicine and blood plasma volume expanders. Its broad
platform of stem cell technologies is developed through subsidiaries focused
on specific fields of applications. BioTime develops and markets research
products in the field of stem cells and regenerative medicine, including a
wide array of proprietary ACTCellerate™ cell lines, culture media, and
differentiation kits. BioTime's wholly owned subsidiary ES Cell International
Pte. Ltd. has produced clinical-grade human embryonic stem cell lines that
were derived following principles of Good Manufacturing Practice and currently
offers them for use in research. BioTime's therapeutic product development
strategy is pursued through subsidiaries that focus on specific organ systems
and related diseases for which there is a high unmet medical need. BioTime's
majority owned subsidiary Cell Cure Neurosciences, Ltd. is developing
therapeutic products derived from stem cells for the treatment of retinal and
neural degenerative diseases. Cell Cure's minority shareholder Teva
Pharmaceutical Industries has an option to clinically develop and
commercialize Cell Cure's OpRegen™ retinal cell product for use in the
treatment of age-related macular degeneration. BioTime's subsidiary OrthoCyte
Corporation is developing therapeutic applications of stem cells to treat
orthopedic diseases and injuries. Another subsidiary, OncoCyte Corporation,
focuses on the diagnostic and therapeutic applications of stem cell technology
in cancer, including the diagnostic product PanC-Dx^TM currently being
developed for the detection of cancer in blood samples, and therapeutic
strategies using vascular progenitor cells engineered to destroy malignant
tumors. ReCyte Therapeutics, Inc. is developing applications of BioTime's
proprietary induced pluripotent stem cell technology to reverse the
developmental aging of human cells to treat cardiovascular and blood cell
diseases. BioTime's newest subsidiary, LifeMap Sciences, Inc., is developing
an online database of the complex cell lineages arising from stem cells to
guide basic research and to market BioTime's research products. In addition to
its stem cell products, BioTime develops blood plasma volume expanders, blood
replacement solutions for hypothermic (low-temperature) surgery, and
technology for use in surgery, emergency trauma treatment and other
applications. BioTime's lead product, Hextend®, is a blood plasma volume
expander manufactured and distributed in the U.S. by Hospira, Inc. and in
South Korea by CJ CheilJedang Corp. under exclusive licensing agreements.
Additional information about BioTime, ReCyte Therapeutics, Cell Cure,
OrthoCyte, OncoCyte, BioTime Asia, LifeMap Sciences, and ESI can be found on
the web at www.biotimeinc.com.

Forward-Looking Statements

Statements pertaining to future financial and/or operating results, future
growth in research, technology, clinical development, and potential
opportunities for BioTime and its subsidiaries, along with other statements
about the future expectations, beliefs, goals, plans, or prospects expressed
by management constitute forward-looking statements. Any statements that are
not historical fact (including, but not limited to statements that contain
words such as "will," "believes," "plans," "anticipates," "expects,"
"estimates") should also be considered to be forward-looking statements.
Forward-looking statements involve risks and uncertainties, including, without
limitation, risks inherent in the development and/or commercialization of
potential products, uncertainty in the results of clinical trials or
regulatory approvals, need and ability to obtain future capital, and
maintenance of intellectual property rights. Actual results may differ
materially from the results anticipated in these forward-looking statements
and as such should be evaluated together with the many uncertainties that
affect the business of BioTime and its subsidiaries, particularly those
mentioned in the cautionary statements found in BioTime's Securities and
Exchange Commission filings. BioTime disclaims any intent or obligation to
update these forward-looking statements.

To receive ongoing BioTime corporate communications, please click on the
following link to join our email alert list:
http://phx.corporate-ir.net/phoenix.zhtml?c=83805&p=irol-alerts

Contact:

BioTime, Inc.
Peter Garcia, 510-521-3390, ext 367
Chief Financial Officer
pgarcia@biotimemail.com
or
Judith Segall, 510-521-3390, ext 301
jsegall@biotimemail.com
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