Stem CellLinesFor friends and supporters of the Harvard Stem Cell Institute

Spring-Summer 2008

I N S I D E

Winter-Spring/2008 1

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Regeneration is, of course, the Holy Grail of medicine. Many diseases are chronicbecause they are a consequence of damage to organs or tissues beyond any naturalrepair mechanism. When kidneys are damaged beyond repair, the only answer

may be transplantation (severely restricted due to the scarcity of donors) or dialysis – aterrible burden on patients (over 350,000 in the U.S.) who are forever tethered to theircondition by weekly and sometimes daily visits to a machine. Harnessing the power ofthe kidney’s innate ability to regenerate could enable patients to regain their health.

“The kidney actually ranks very highly in its ability to repair itself,” said JosephBonventre, MD, PhD Professor of Medicine at Harvard Medical School, Chief of theRenal Division at Brigham and Women’s Hospital, and head of the HSCI Kidney Disease Program.

Bonventre and his team study the mechanisms by which the kidney repairs tissueafter disease, particularly the repair of nephrons, which are the key functional units ofthe kidney. The nephron consists of a filtering unit for the blood, the glomerulus, and a

The Kidney Repair Shop

c o n t i n u e d o n p a g e 2

Joseph Bonventre, MD, PhD and Benjamin Humphreys, MD, PhD are studying how the kidney repairs

tissue after disease.

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Stem CellLinesHarvard Stem Cell InstituteExecutive Director

Brock C. Reeve, MPhil, MBA Scientific Directors

Douglas A. Melton, PhDDavid T. Scadden, MD

The Harvard Stem Cell Institute (HSCI) is a scientific collaborative established in 2004 to fulfillthe promise of stem cell biology as the basis forthe cure and treatment of a wide range of chronicdiseases and medical conditions. HSCI’s uniqueeffort unites experts across the disciplines, schoolsand departments of Harvard University and all itsaffiliated research hospitals.

HSCI also sponsors public education programsconcerning scientific, legal, and ethical implicationsof stem cell research, conducts a summer researchprogram for college students, and helps educatearea high school teachers about stem cell science.HSCI depends on the vision and generosity of private individuals, and foundation and corporatedonors to carry on its work, due to current U.S.restrictions on federal funding of embryonic stemcell research.

Stem Cell Lines is published three times each year for friends and supporters of HSCI.Inquiries from the public are encouraged; e-mailbrock_reeve@harvard.edu.

Stem Cell Lines and extensive information concern-ing HSCI scientific research and programs can befound at www.hsci.harvard.edu.

To be added to or removed from the mail list, contact:

Harvard Stem Cell Institute42 Church StreetCambridge, MA 02138Tel: 617.496.4050

Managing EditorBrock C. Reeve

EditorMaureen Lyons

© 2008 President and Fellows of Harvard College

Spring-Summer 2008

Stem CellLines

WritingKatherine ChenRaymond CoderreLisa GirardMaureen HerrmannMaureen LyonsMichael Silver

DesignAndrade Design

complex tubule responsible for filtering the blood.

The small tubules collect the filtrate and process it

before passing it on to ducts leading to the bladder.

“If tubules are damaged they can be repaired but if

the damage is severe enough the nephron may be

destroyed. Unfortunately the kidney can regenerate

and recover, but the kidney cannot make new

nephrons, and in that context, its regeneration

is limited.”

What happens to the tubules is a clinically

relevant question. In kidney disease, whether the dis-

ease starts in the filters or the tubules, the tubules

ultimately become involved as they are highly suscepti-

ble to injury. A reduction in blood flow can lead to a

restriction in the supply of oxygen, which can be lethal

to the epithelial cells that form the lining of the

tubules. For acute kidney injury, the tubules are often

(but not always) capable of recovering completely. In

chronic kidney failure, the injuries are progressive and

nephrons are lost.

Many theories exist on kidney repair. Some

suggest that the kidney may recruit circulating stem

cells to migrate into and regenerate the damaged area,

others that local tissue specific stem cells may be trig-

gered to differentiate and rebuild, and still others that

the kidney may forego a direct role for stem cells alto-

gether by inducing mature cells to proliferate.How-

ever, a recent study by Bonventre, HSCI Affiliated

Faculty member Benjamin Humphreys, MD, PhD,

HSCI Executive Committee Member Andrew

McMahon, PhD, and their team went a long

way toward understanding how the tubules

repair themselves.

By tagging the mature epithelial cells that form the

tubule walls with a red fluorescent protein, the HSCI

team was able to demonstrate that the replacement

cells after injury are coming from the epithelium itself

rather than from circulating stem cells that enter the

kidney or local tissue specific stem cells in the tissue

between the tubules. These stem cells might not be sit-

ting on the sidelines, however. Other evidence suggests

that they may be offering some assistance in causing

the epithelial cells to multiply.

In over 35 years of studying the repair of damaged

kidneys, Bonventre suggests that the field may be

reaching an inflection point. “The Harvard Stem Cell

Institute basically has allowed us to look at kidney dis-

ease in a different and, in many cases, quite definitive

way,” said Bonventre. “We’re understanding the

processes much better so that we can now focus on the

cell biology related to the intrinsic capacity for the

kidney to renew itself.”

Collaboration among HSCI researchers has been

key to advancing this understanding by sharing

expertise as well as findings from model organisms

such as the mouse and the zebrafish. “Andy McMahon

is a world class investigator who has made enormous

contributions to the understanding of the way the kid-

ney matures during development,” said Bonventre. “It

has been very productive to apply this knowledge to

understanding repair in the adult organ.”

The team is also using knowledge of the kidney’s

ability to renew itself to find out how to protect it from

further damage. “We have found in mice that we can

precondition the kidney to be protected against a sub-

sequent injury simply by temporarily cutting off blood

flow to parts of the organ and coming back one to two

weeks later and finding that when we cut off blood

supply again the kidney is not damaged,” said

Bonventre. “We want to understand what causes the

protection against the second injury. Is there a

cell that goes into the kidney, or some other factor

involved?” If these protective factors can be found,

they could potentially be developed as drugs or

treatments that prevent kidney damage in high-

risk individuals.

Another use of kidney cells grown in the labor-

atory is in screens for the potential toxicity of drugs

before they are introduced into animals or humans.

There really is no good model for in vitro kidney toxici-

ty screening today, because the cells tend to lose their

differentiated state and become less “kidney-like” or

less “epithelial-like” outside the body. Bonventre and

colleagues are working on ways to control cell behavior

and maintain their state to make better predictive

screens. “We will be working with Lee Rubin’s group

at the HSCI Therapeutic Screening Center to help us

screen for molecules that will keep cells differentiated

in culture. If we can do that, we can use them for tox-

icology and for more sophisticated kidney assist

devices,” said Bonventre.

Taking that technology back inside the body, one

might even use the differentiated cells to create artifi-

cial tubules and nephrons with the help of bioengi-

neered materials - completing the regeneration that the

kidney is unable to do on its own.

Patients might not have to wait too long to see

the benefits of this research. Based on animal studies

that suggested an indirect role for stem cells in kidney

repair, clinical trials aimed at preventing or rolling

back kidney damage in cardiac patients have

already begun.

The Kidney RepairShopc o n t i n u e d f r o m c o v e r

“The Harvard Stem Cell Institute basically has allowed us to look at kidney disease in a different and, in many cases, quite definitive way.”

– Joseph Bonventre, MD, PhD

Volume 3Number 2

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For friends and supporters of the Harvard Stem Cell Institutes

c o n t i n u e d o n p a g e 8

A nyone who has owned a car or a house knows that unless you

constantly maintain it and conduct repairs, it is not going to

last very long. That’s true for our bodies as well. In fact, there is

evidence to suggest that within many of our tissues and organs live a rel-

atively small number of adult stem cells that can repair or replace tissues

and parts of organs damaged by injury or disease. These cells, which

may represent sentries remaining from our embryonic development,

also play an essential role in what is termed “homeostatic mainten-

ance” – keeping our organs

in a constant state of health

through renewal.

To scientists seeking new

treatments for disease, these

tissue-specific adult stem

cells present several oppor-

tunities. For example, it may

be possible to identify fac-

tors that stimulate the

growth and activity of these

cells so their role in the

repair of damaged tissues

can be enhanced. Another

benefit could be derived

from isolating these tissue

specific stem cells and using

them to generate cell lines that can be maintained in the laboratory, and

used for screening new drugs for toxicity or effectiveness before they are

tested in humans.

The Search is On Organ tissues can be roughly organized into three

categories: those that have many active tissue-specific stem cells, those

that have very few or declining populations, and those that have none.

The blood system has perhaps the richest source of tissue-specific

stem cells. Hematopoietic or blood-forming stem cells and mesenchymal

stem cells that form bone, cartilage, and fat, can all be found in the bone

marrow, a component of the blood system. Because of the relatively large

number and active nature of the hematopoietic stem cells, it has been

possible to use them to treat cancers and other diseases of the blood and

immune system. The skin and gut similarly, are constantly renewing at a

high rate.

In contrast to the blood system, skeletal muscle stem cells are much

more rare and lose their ability to repair muscle injuries over time, as

they decline in both number and function with age. However, identify-

ing these tissue specific stem cells and studying what controls their

capacity for regeneration could open the door for new treatments that

encourage self-repair.

At far end of the spectrum is the pancreas, which many scientists

believe has no tissue-specific stem cell. This situation presents a particu-

larly difficult challenge in developing treatments for diabetes – a disease

where pancreatic beta cells are destroyed.

Niches in Dishes How does a stem cell know when to kick into action

and repair damaged tissues and organs? That’s a question that many sci-

entists are asking, and some of the theories they are coming up with

have been borrowed from the field of ecology. In an ecosystem, the sur-

vival and behavior of each organism is dependent on interactions with its

environment or “niche.” It has been proposed that stem cells know when

and how to act by communicat-

ing with their environment,

including the surrounding cells.

The “niche” normally keeps the

stem cells in a balanced state of

self renewal, perhaps splitting off

specialized cells in regular inter-

vals by an internal ‘clock.’ But

when change occurs, the niche

can activate stem cells, causing

them to move to where they are

needed and to differentiate into

specialized cells to complete

the repair.

Researchers are now working

to reproduce stem cell niches in

the laboratory. If the factors and

conditions that control stem cell behavior can be isolated, the cells could

be developed for therapeutic use, for screening new drugs, or for the cre-

ation of biomaterials that can replace complex structures within the body

that can not be reconstructed by a simple infusion of stem cells.

The Stem Cell as Helper In some cases, stem cells do not appear to be

taking center stage in the repair and regeneration of tissue but are key

players nonetheless. In the kidney, it was found that when the tubules

used for drawing off waste fluids from the blood are damaged, it is the

mature epithelial cells, not stem cells, which step in to rebuild the tissue.

However, stem cells are thought to play a role in helping the epithelial

cells to “de-differentiate” before they multiply and transform back into

mature epithelial cells again.

Moving Forward on Multiple Fronts Because not all tissue-specific

stem cells are the same, scientists must employ different strategies

depending on the organ or disease in question. Hematopoietic stem cells

allow the blood system to constantly replenish itself throughout a per-

son’s life. Therefore these cells are not only studied with the intent of

increasing the efficiency of transplants and generating new cell-based

therapies for blood diseases, but also so that their remarkable capacity

for self-renewal can be modeled and applied to other organ systems.

In cases where there are few tissue-specific stem cells or those pres-

ent are inactive, such as in skeletal muscle, the goal is to determine what

The Seeds of Regeneration

To scientists seeking new

treatments for disease, these

tissue-specific adult stem cells

present several opportunities.

For example, it may be possible

to identify factors that stimulate the growth and

activity of these cells so their role in the repair of

damaged tissues can be enhanced.

4 Spring-Summer/2008

Stem CellLines2008 HSCI SeedGrant RecipientsAnnounced:First MilliporeFoundationFellowship awarded

For the fourth consecutive year, HSCI

awarded seed grants to scientists

throughout the Harvard community

to provide critical early funding for

stem cell research. In May, ten seed

grants totaling nearly $2 million were

awarded to investigators, selected

from a pool of 64 applicants from HSCI-affiliated institutions.

This year’s grants will support stem cell research related to a variety of

targeted disease areas such cancer, cardiovascular disease, kidney, nervous

system disorders, skeletal disease, and bioengineering.

HSCI’s Seed Grant Program provides two years of funding for projects

in areas of stem cell research that will advance HSCI’s mission. A multi-

institutional panel conducts a rigorous review process with the difficult

task of selecting a set of the most promising projects from many superbly

qualified applications. Highest priority is given to projects that are diffi-

cult to fund from other sources because they are early stage, high risk, or

are ineligible for federal support because of restrictions on human embry-

onic stem cell (hESC) research. The grants are also intended to support

junior faculty in the early stages of their independent careers but also

support senior faculty entering brand new, otherwise unfunded, areas

of research.

In 2007, the Millipore Foundation made a generous gift of $500,000

to the HSCI Seed Grant Program to support one recipient per year for the

next five years. 2008 Seed Grant recipient Sangeeta Bhatia, MD, PhD, of

Brigham and Women’s Hospital has been named HSCI’s first Millipore

Foundation Seed Grant Fellow.

2008 HSCI Seed Grant Recipients

Paola Arlotta, PhD, Massachusetts General Hospital

Sangeeta Bhatia, MD, PhD, Brigham and Women’s Hospital

Caroline Burns, PhD, Massachusetts General Hospital

Stephen Haggerty, PhD, Massachusetts General Hospital

Xue Li, PhD, Children’s Hospital Boston

Judy Lieberman, PhD, Immune Disease Institute

William Pu, MD, Children’s Hospital Boston

Zhong Wang, PhD, Massachusetts General Hospital

Rebecca Wingert, PhD, Massachusetts General Hospital

Sean Wu, MD, PhD, Massachusetts General Hospital

Stem Cells as Tools

For many people, the idea that someday incurable diseases will be

cured by regenerative medicine and cell-based therapies is what

makes stem cell research so exciting. But there is another avenue

of research being pursued that is equally promising, where stem cells

aren’t the treatment, but rather the tool that will help uncover

potential cures.

An important technology in stem cell research and drug discovery is

high throughput screening (HTS), which is done using special plates

that contains 384 small divots called wells. Cells, proteins, or other

biological material are first put into the wells, and then different small

molecules, drugs, or biologics are added. Each well is like a miniature

experiment. This powerful technology makes it possible to test thou-

sands of small molecules in a short amount of time.

At HSCI’s Therapeutic Screening Center, headed by Lee Rubin, PhD,

Director of Translational Medicine at HSCI, researchers perform screen-

ing assays against stem cells or cells grown from stem cells in order to

identify small molecules, compounds, gene products, and proteins that

could be turned into diverse therapeutics to cure diseases.

The use of stem cell lines allows for a new type of screening because

large populations of similar cells are required in order to generate useful

and accurate data. Our ability to grow both embryonic and adult stem

cells now makes it possible to achieve both the quality and quantity of

cells needed. For example, in order to run drug toxicity screens against

human cardiac or neuronal cells, stem cells could be directed to differ-

entiate into the needed cell type. This creates a large enough population

of cells to use in the screen, and does it in a reproducible way – a criti-

cal element when conducting experiments.

Another reason why stem cells are so important to HTS is that “dis-

ease-specific” cell lines can create in vitro models of diseases. These stem

cell lines are generated from patients with a given disease – either

through somatic cell nuclear transfer or reprogramming – or from an

embryo that has tested positive for a disease. Facilities such as HSCI’s

Therapeutic Screening Center can use these cell lines to study the cause

of the disease and search for possible therapeutics.

One way that screening assays use disease-specific cell lines is to

look for drugs that help to treat a given disease. For example, at the

Therapeutic Screening Center, researchers are using a screen focused on

identifying molecules or pathways that prevent degeneration of stem

cell-derived motor neurons that carry the mutation causing Spinal

Muscular Atrophy (SMA). The screen tests for molecules that can cause

more motor neurons to live and express higher levels of the protein that

is missing, or under-expressed, in the disease. Testing early in the drug

development cycle is much more effective and efficient than testing later

in humans and potentially discovering problems after significant time

and money have been committed.

Other types of screens address questions about the underlying

mechanism of disease. In the case of SMA, many questions exist about

why the motor neurons are so sensitive to the SMA mutations relative to

other cells and whether this is due to cell-specific regulatory pathways

or unique functions in motor neurons. The stem cell-based screens

done by Rubin and his team are addressing these questions on two

levels. The first asks mechanistic questions about SMA biology, in order

to determine how SMA influences motor neurons. The second explores

Sangeeta Bhatia, MD, PhD, ofBrigham and Women’s Hospitalhas been named HSCI’s firstMillipore Foundation Seed Grant Fellow.

Spring-Summer/2008 5

For friends and supporters of the Harvard Stem Cell InstitutesPublic Forum: Stem Cells and Key Diseases

HSCI researchers are exploring options to treat diabetes, nervous

system diseases, cardiovascular disease, and other degenerative dis-

eases in a variety of ways, including stimulating existing stem cells,

transplanting new cells, and targeting specific stem cell populations. At

a recent public forum on “Stem Cells and Key Diseases,” moderated by

Kevin Eggan, PhD, HSCI brought together three of its disease program

heads to discuss the state of science in both the laboratory and in the

clinic, and to identify areas of progress and potential.

Gordon Weir, MD, head of HSCI’s Diabetes Program, addressed the

progress and goals of diabetes-focused stem cell research. In order to

treat diabetes by increasing the number of insulin-producing beta cells

in the pancreas, Weir explained, researchers are actively investigating

two main strategies - how to create new cells for implantation and how

to encourage existing beta cells to multiply.

Drawing an analogy between stem cell research and the develop-

ment of heart transplantation surgery techniques, Kenneth Chien, MD,

PhD, head of the Cardiovascular Program at HSCI, said he expects

stem cell research to transform our understanding of cardiovascular

disease over the next 10 years, potentially leading to new drugs and

treatment strategies.

In discussing the complexity of the nervous system, Jeffrey

Macklis, MD, DHST, head of the HSCI’s Nervous System Diseases

Program, explained that many hundreds, if not several thousands, of

different types of neurons exist in the brain. Macklis compared this

diversity of nerve cell types to different types of vehicles, ranging from

a sedan to a fire truck, each with a specific function and capability.

Macklis stressed that researchers face the problem of determining

which kind of vehicle they want and whether it is needed for a

replacement part or for use in disease study. In discussing Amyo-

trophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease,

and other diseases of upper and lower motor neurons, Macklis profiled

ongoing research at HSCI that is attempting to make both spinal and

corticospinal motor neurons, as well as research aimed at studying

what drugs might help preserve them or enhance their growth.

how these mechanistic insights can be translated into the search for

therapeutic targets.

Screens can also be used to search for drugs or biologics that direct

stem cells into becoming a specific type of cell – a process known as

targeted differentiation. Knowing how to generate a certain type of cell

from stem cells is very important for treating conditions where cells

have been injured or died, such as in diabetes.

The challenge in diabetes is to replace pancreatic beta cells, the cells

that make insulin to regulate the body’s blood sugar, which are

destroyed in the disease process. To address this challenge, Douglas

Melton, PhD, co-Scientific Director of HSCI, and HSCI Affiliated Faculty

Richard Maas, PhD, are working with Rubin and his team to conduct

two types of screens. In the first they are looking for factors that stimu-

late beta cells to proliferate into more beta cells – knowledge that could

be used to create a self-repair type therapy. The second types of screens

are looking for ways to direct the differentiation of stem cells into pan-

creatic beta cells, which could be used in cell-replacement therapeutics.

The Therapeutic Screening Center is an important hub of collabora-

tion at HSCI, as the state-of-the-art technology is an invaluable resource

across different disease areas and model organisms. When stem cells are

used as tools, researchers are able to ask key questions about disease

mechanisms by

modeling diseases

more faithfully than

in the past. And the

answers to these

questions will even-

tually identify new

treatments for dis-

eases that have been

previously difficult

to study.

Cells are put in plates and exposed to factors (top left). Hits, includingcontrols, are shown as green squares (top right). Increased numbers ofcells express green fluorescent protein (GFP) in a hit (bottom right) relative to a control.

HSCI’s Therapeutic Screening Center, led by LeeRubin, identifies factors directing stem cell proliferation and differentiation, with the goalof using these factors to cure disease.

At HSCI's recent Public Forum, Jeffrey Macklis, MD, DHST discussedsome of his research in the area of nervous system diseases.

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Stem CellLines

T he power of an international colloquium

of pre-eminent scientists can be transfor-

mative. Nowhere was that more evident

than in the three recent HSCI Think Tanks con-

vened by Jeffrey Macklis, MD, DHST, head of

HSCI’s Nervous System Diseases Program and

Kenneth Chien, MD, PhD, head of HSCI’s

Cardiovascular Disease Program.

In June of 2006 and again in June of 2007, a

team of experts gathered for the HSCI Parkinson’s

Disease (PD) Think Tank, sponsored by the Golub

Fund for Parkinson’s Disease Research, to explore

the “Molecular Biography of the Dopaminergic

Neuron.” Each 2-day program began with a public

seminar at the Harvard Medical School followed

by intimate and animated small group discussions

at the Harvard Humanities Center.

Committed to discarding a ‘business as

usual’ approach to disease research, Macklis set a

new tone.

“What can Harvard, with its network and

resources, bring to the table that will advance

knowledge in the field?” Macklis asked. “We want

to think in a global fashion: to identify the knowl-

edge gaps and to ask how Harvard can make a

significant contribution to PD research. If we were

to dream, what would those dreams be?”

“These individuals distilled the state of the art

knowledge in Parkinson’s disease and dopaminer-

gic neuron development and freely provided the

most exciting areas of investigation for Harvard,

and indeed, the larger scientific community,” said

HSCI Affiliate Faculty U. Shivraj Sohur, MD, PhD,

after attending the both the 2006 and 2007

think tanks.

Turning Think Tank thoughts and ideas into

action and coming away with a renewed enthusi-

asm and validation of preliminary experiments

being done in the lab, Sohur proposed and was

awarded an HSCI grant to study how the

Parkinson’s disease dopaminergic neurons (SNc)

develop after they are born in the midbrain.

Sohur’s goal is to isolate purified populations

of SNc neurons at important stages in their matu-

ration, allowing study of their genetic expression

profile and determine the mechanisms of their

maturation. This knowledge could eventually

enable therapeutic strategies in Parkinson’s disease

and other related degenerative movement disor-

ders. The project includes collaboration with Dr.

Anders Björklund, MD, PhD, of the University of

Lund in Sweden, a pioneer in dopamine neuron

biology and attendee of the 2006 PD Think Tank.

In April 2007, HSCI hosted its first

Cardiovascular Think Tank, “Re-engineering of the

Cardiovascular Stem Cell Biology at Harvard.”

Renowned cardiovascular and bio-engineering

experts from across the globe gathered at the

Radcliffe Institute for Advanced Study for an

intensive, day-long exercise. The program, chaired

by Chien, focused on the identification of key car-

diovascular stem cell topic areas that would most

benefit from HSCI collaborative initiatives. Plans

are being developed to re-convene the group and

identify specific projects that will keep HSCI at

the vanguard of cardiovascular stem cell research

in collaboration with other global leaders.

Based on the success of these programs, the

HSCI is planning on expanding its Think Tank

sessions to include programs on ALS, Diabetes,

and other disease areas. The next Think Tank will

be on Motor Neuron Disorders on June 9 and 10

and will be chaired by Macklis.

A New Home for HSCI

The new building will house HSCI, SCRB,and other multi-disciplinary scienceinitiatives.

Construction of the slurry wall alongWestern Avenue is under way.

After attending HSCI’stwo Parkinson’sDisease Think Tanks, U.Shivraj Sohur, MD, PhDwas awarded an HSCIgrant to study howthe Parkinson’s dis-ease dopaminergicneurons develop afterthey are born in themidbrain.

HSCI Think Tanks: Accelerating the Process of Discovery

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For friends and supporters of the Harvard Stem Cell Institutes

C onstruction for HSCI’s new home in the First

Science building in Allston is well under

way. The new building will house both the

Harvard Stem Cell Institute, the newly-formed

Department of Stem Cell and Regenerative Biology

(SCRB) and other multi-disciplinary science initia-

tives. Located on the future Harvard campus in

Allston, the First Science building was designed

specifically to facilitate interdisciplinary and collabo-

rative research and will contain faculty laboratories,

shared core facilities, administrative offices, a confer-

ence center, and dedicated seminar and teaching

space. Building on the success of the HSCI, the

anticipated move to Allston in the summer of 2011

presents an opportunity for the institute to expand

and strengthen the already vibrant community of

stem cell scientists involved in its research and

education programs.

“It is rare to be given the opportunity to think

through a laboratory building from the ground up,”

according to David Scadden, co-director of the

Harvard Stem Cell Institute and co-chair of the

Department of Stem Cell and Regenerative Biology.

“Because faculty members have been involved in this

planning process from the beginning, we will end

up with a world-class facility that’s designed to meet

Harvard’s evolving needs in science, rather than a

building that has to be retrofitted as needs change

over time,” said Scadden.

The co-location of HSCI and the new

department in First Science will facilitate better

connections across the University, including the

numerous schools and hospitals that are

involved in interdisciplinary education and

research. Bringing together many members

of the HSCI community to work in one location

will enable them to intensify their collaborations,

and will provide new opportunities for under-

graduates, graduate students, and medical

students to receive training in stem cell biology

and regenerative medicine.

The HSCI will continue to be much broader

than the First Science building itself. “With our

60 Principal Faculty, the entire Institute couldn’t

even fit in the new building,” says Brock Reeve,

Executive Director. Some HSCI scientists will

transfer their full research programs to Allston,

others will split their labs between Allston and

their current locations, and others will continue

to be integral members of the HSCI community

but will maintain their labs where they are.

Moving from a virtual network to more of a hub-

and-spoke model will allow HSCI to maintain its

connections to the hospital labs, clinics and core

facilities across the University and affiliates while

providing a center of gravity to its efforts.

Which other faculty and initiatives will move

into the complex has not yet been finalized, but

the University is currently in discussions – with

other multi-disciplinary research groups – in-

cluding Systems Biology and Bioengineering –

about joining HSCI and SCRB in First Science.

These groups recently presented to a committee

of senior administrators and faculty some ideas

about the exciting new joint research and teach-

ing opportunities that this new building offers as

a result of having a critical mass of inter-discipli-

nary scientists in related fields working close to

one another. “This is an example of what collab-

orative, multi-disciplinary science can look like

at Harvard,” said Douglas Melton, PhD,

co-Scientific Director of HSCI.

The American Academy of Arts & Sciencesannounced the election of 190 new Fellows and 22 Foreign Honorary Members, includingLeonard Zon, MD, Chair of HSCI’s FacultyExecutive Committee.

Awards and Honors

Kenneth R. Chien, MD, PhD, the head of HSCI’sCardiovascular Disease Program, will be awardedan Honorary Doctor of Science degree by theUniversity of Edinburgh this coming July.

Mount Sinai School of Medicine recognized HSCI’sCo-Director Douglas Melton, PhD, for his visionand compassion by honoring him with the degreeof Doctor of Science.

Co-Director David Scadden, MD will be honoredwith a Doctor of Science degree by his alma materBucknell University for his leading work in thefield of stem cell research.

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Stem CellLines

Upcoming HSCI Events

For details about these and other

upcoming events, visit the HSCI

website at www.hsci.harvard.edu

or call us at 617.496.4050.

August 20 HSCI Internship Program

Symposium

Harvard University, Cambridge

September 22Third Annual HSCI Stem Cell Summit

Hynes Convention Center, Boston

November 7Fifth Annual Tony & Shelly

Malkin Symposium

Harvard Club of Boston

Fall HSCI Stem Cell Public Forum

Details about this free event for the

general public will be available

soon on the HSCI website.

factors will initiate or increase the level of their regenerative capacity. HSCI faculty are interested

in understanding how to encourage replication of these small populations not only for therapeu-

tic possibilities but also for use in screening and toxicology assays (see Stem Cells as Tools on

page 4).

When an organ, such as the pancreas, does not have a tissue-specific stem cell, research is

directed at how to stimulate replication of the mature cells, such as pancreatic beta cells, that

have not been destroyed, or how to derive new beta

cells from “unprogrammed” embryonic stem cells.

The need to identify and characterize tissue-spe-

cific stem cells applies across organs, tissue types,

and diseases. At the same time, it is important to

understand the limitations of each stem cell type.

Several HSCI faculty have engaged in many experi-

ments to understand the specificity of tissue-specific

stem cells. In other words, can a blood stem cell

contribute to cardiac repair, or a skin stem cell to

another organ? By and large, it seems that tissue-specific stem cells are in fact committed to pro-

ducing cells within a particular tissue type. In many senses, this is an advantage for using these

cells for tissue repair, as transplanted tissue-specific stem cells will already “know” which cells

they should produce. However, this also means that attempts, some of which are even in clinical

trials, to introduce cells of one type into a distinct organ system to effect repair are likely mis-

guided. A better understanding of how stem cells contribute effectively to organ repair will

depend increasingly on capable analytical tools such as in vivo cell imaging that can show where

cells go, how they engraft, how they transform, and how they survive and procreate.

Macklis emphasized that success in this field will result not only in the replacement of diseased

neurons but also in the discovery of drugs for the amelioration or prevention of neuronal death

and degeneration through the use of specialized nerve cells for disease study.

While each of the panel members agreed that the therapeutic use of stem cells is many years

away, there was also consensus that current research in the field has and will continue to result

in many useful clinical tools for disease study. Advances in stem cell research have provided

researchers with an opportunity to study the progression of disease at the cellular level, resulting

in increased knowledge about the nature of disease progression as well as the potential for

finding novel methods of treatment.

A video of the public forum is available online at: http://www.hsci.harvard.edu/node/45.

c o n t i n u e d f r o m p a g e 3The Seeds of Regeneration

c o n t i n u e d f r o m p a g e 5Public Forum: Stems Cells and Key Diseases

Our ability to grow

both embryonic and

adult stem cells now makes

it possible to achieve both

the quality and quantity of

cells needed.