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Royan Newsletter Vol 3 No 2 Spring 2010 (88-12 ... - Royan Institute

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1<br />

<strong>Vol</strong>. 3, <strong>No</strong>.2, <strong>Spring</strong> <strong>2010</strong><br />

از چرخ به هر گونه همى دار اميد<br />

پس موى سياه من چرا گشت سفيد<br />

وز گردش روزگار مى لرز چو بيد<br />

گفتى كه پس از سياه رنگى نبود<br />

With fate you still hope to trade;<br />

You said no color comes after black,<br />

Passage of time should make you afraid<br />

I said my black hair to white degrade]<br />

Hafiz (1320-1389 A.D)<br />

Granulocyte-Colony Stimulation Factor (G-CSF)<br />

for Treatment of Chronic Lower Limb Ischemic<br />

Patients<br />

Autologous Transplantation of Cultivated Limbal<br />

Stem Cells on Amniotic Membrane in Limbal Stem<br />

Cell Deficiency (LSD) Patients<br />

Finished Projects<br />

Esfahan, Iran - Sep 2009<br />

An Amazing Trip<br />

“…Regarding my trip to Iran, I had a great time. The<br />

conference was thoroughly interesting as was my visit<br />

to the <strong>Royan</strong> <strong>Institute</strong> and the Regenerative Medicine<br />

Centre… Regarding the post-congress tour, it was<br />

truly amazing. Esfahan, Shiraz and Persepolis were<br />

beautiful places to visit and I remember them fondly. I<br />

am also grateful to you all at the <strong>Royan</strong> <strong>Institute</strong> for all<br />

the wonderful friends I was able to make both Iranian<br />

and the international delegates. In particular, I would<br />

like to thank you Kamal for showing us the beautiful<br />

sites of Iran. Best regards,<br />

Dr Sajjad Ahmad, PhD,<br />

<strong>No</strong>rth East England Stem Cell <strong>Institute</strong> and <strong>Institute</strong> of<br />

Human Genetics,<br />

Newcastle University, Bioscience Centre, International<br />

Centre for Life,<br />

Times Square, Newcastle upon Tyne, NE1 4EP, United<br />

Kingdom<br />

Research Projects in <strong>Royan</strong><br />

<strong>Institute</strong>:<br />

Projects on Process<br />

Autologous Transplantation of Bone Marrow<br />

Mononuclear Cell (BM-MNC) With and Without<br />

Evaluation of factors that induce differentiation<br />

of mouse embryonic stem cells to cholinergic<br />

neuron<br />

Three- dimensional & monolayer culture of<br />

chndrocytes isolated from Rat articular cartilage<br />

The effect of superovulation on blastocyst quality<br />

of NMM mouse In Vitro<br />

<strong>Royan</strong> Articles<br />

Reprod Biomed Online. 2009 <strong>No</strong>v;19(5):734-6.<br />

Appropriate timing of uterine cavity length<br />

measurement positively affects assisted<br />

reproduction cycle outcome.<br />

Madani T, Ashrafi M, Abadi AB, Kiani K.<br />

Edocrinology and Female Infertility Department,<br />

Reproductive Medicine Research Centre, <strong>Royan</strong> <strong>Institute</strong>,<br />

ACECR, Tehran, Iran. tmadani@royaninstitute.org<br />

An appropriate and easy embryo transfer has a direct<br />

impact on pregnancy rates. Proper evaluation of the<br />

uterocervical axis and uterine depth are necessary<br />

for suitable embryo transfer. The aim of this study<br />

was to assess the appropriate time for cervical axis<br />

evaluation and uterine measurement. A total of <strong>12</strong>4<br />

<strong>Royan</strong> <strong>Institute</strong><br />

Reproductive Biomedicine Stem Cell Biology<br />

& Technology Tehran, Iran<br />

P.O.Box: 19395 - 4644<br />

Tel/Fax: (+9821) 22310406<br />

E-mail: info@royaninstitute.org


patients undergoing IVF treatment were included in<br />

the study. They were divided equally into two groups.<br />

In group I (62 women), uterine cavity depth was<br />

measured and the uterocervical axis was determined<br />

on day 2 or 3 of the menstrual cycle, and in group II<br />

(62 women) at the time of oocyte retrieval. There was a<br />

statistically significant difference in clinical pregnancy<br />

rates between the two groups (P = 0.006). Thirty-four<br />

women became pregnant in group I (64.2%) versus<br />

19 women in group II (35.8%). In conclusion, uterine<br />

cavity measurement is necessary for suitable embryo<br />

transfer. It seems that the time of measurement<br />

significantly affects clinical pregnancy rate in IVF<br />

cycles. The best time for uterine measurement is on<br />

day 2 or 3 of menstruation.<br />

Biochem Biophys Res Commun. <strong>2010</strong> Jan<br />

1;391(1):329-34. Epub 2009 <strong>No</strong>v 11.<br />

Generation of human induced pluripotent stem<br />

cells from a Bombay individual: Moving towards<br />

“universal-donor” red blood cells.<br />

Seifinejad A, Taei A, Totonchi M, Vazirinasab H, Hassani<br />

SN, Aghdami N, Shahbazi E, Yazdi RS, Salekdeh GH,<br />

Baharvand H.<br />

Department of Stem Cells and Developmental Biology,<br />

<strong>Royan</strong> <strong>Institute</strong> for Stem Cell Biology and Technology,<br />

P.O. Box 19395-4644, ACECR, Tehran, Iran.<br />

Bombay phenotype is one of the rare phenotypes<br />

in the ABO blood group system that fails to express<br />

ABH antigens on red blood cells. <strong>No</strong>nsense or<br />

missense mutations in fucosyltransfrase1 (FUT1)<br />

and fucosyltransfrase2 (FUT2) genes are known to<br />

create this phenotype. This blood group is compatible<br />

with all other blood groups as a donor, as it does<br />

not express the H antigen on the red blood cells. In<br />

this study, we describe the establishment of human<br />

induced pluripotent stem cells (iPSCs) from the dermal<br />

fibroblasts of a Bombay blood-type individual by the<br />

ectopic expression of established transcription factors<br />

Klf4, Oct4, Sox2, and c-Myc. Sequence analyses of<br />

fibroblasts and iPSCs revealed a nonsense mutation<br />

826C to T (276 Gln to Ter) in the FUT1 gene and a<br />

missense mutation 739G to A (247 Gly to Ser) in the<br />

FUT2 gene in the Bombay phenotype under study.<br />

The established iPSCs resemble human embryonic<br />

stem cells in morphology, passaging, surface and<br />

pluripotency markers, normal karyotype, gene<br />

expression, DNA methylation of critical pluripotency<br />

genes, and in-vitro differentiation. The directed<br />

differentiation of the iPSCs into hematopoietic<br />

lineage cells displayed increased expression of the<br />

hematopoietic lineage markers such as CD34, CD133,<br />

RUNX1, KDR, alpha-globulin, and gamma-globulin.<br />

Such specific stem cells provide an unprecedented<br />

opportunity to produce a universal blood group donor,<br />

in-vitro, thus enabling cellular replacement therapies,<br />

once the safety issue is resolved. Copyright © 2009<br />

Elsevier Inc. All rights reserved.<br />

Int J Dev Biol. 2009 Oct 2. [Epub ahead of print]<br />

Feeder- and serum-free establishment and<br />

expansion of human induced pluripotent stem cells.<br />

Totonchi M, Taei A, Seifinejad A, Tabebordbar M,<br />

Rassouli H, Farrokhi A, Gourabi H, Aghdami N,<br />

Hosseini-Salekdeh G, Baharvand H.<br />

Department of Stem Cells and Developmental Biology,<br />

<strong>Royan</strong> <strong>Institute</strong> for Stem Cell Biology and Technology,<br />

ACECR, Tehran, Iran<br />

Although human induced pluripotent stem cells<br />

(hiPSCs) hold great promise as a source of<br />

differentiated cells for vast therapeutic implications,<br />

many obstacles still need to be surmounted before<br />

this can become a reality. One obstacle, a robust<br />

feeder- and serum-free system to generate and<br />

expand hiPSCs in culture is still unavailable. Here,<br />

for the first time, we describe a novel establishment<br />

and maintenance culture technique that uses human<br />

dermal fibroblasts to generate hiPSCs by introducing<br />

four factors, Klf4, Oct4, Sox2, and c-Myc under serumand<br />

feeder-independent conditions. We have used<br />

a serum replacement product, conditioned medium<br />

(CM), or feeder-free medium (FFM) supplemented<br />

with high elevated basic-fibroblast growth factor in the<br />

absence or presence of Matrigel. Our FFM system in<br />

the presence of Matrigel enhanced the efficiency of<br />

alkaline phosphatase-positive colonies at a frequency<br />

at least 10-fold greater than the conventional<br />

method on feeder cells. The established hiPSCs<br />

are similar to human embryonic stem cells in many<br />

aspects including morphology, passaging, surface<br />

and pluripotency markers, normal karyotype, gene<br />

expression, ultrastructure, and in vitro differentiation.<br />

Such hiPSCs could be useful particularly in the<br />

context of in vitro disease modeling, pharmaceutical<br />

screening and in cellular replacement therapies once<br />

the safety issues have been overcome.<br />

ROYAN<br />

International Twin Congress<br />

11 th Congress on Reproductive<br />

Biomedicine &<br />

6 th Congress on Stem Cells Biology<br />

&<br />

Technology<br />

Sep 15 – 17, <strong>2010</strong> - Tehran – Iran<br />

Deadline 10 May <strong>2010</strong><br />

Email: royancongress@gmail.com<br />

2


Some of our invited speakers in 11 th <strong>Royan</strong> Twin International Congress<br />

15 – 17 Sep <strong>2010</strong>, Tehran, Iran<br />

3<br />

Name From Position<br />

Prof. Rudolf Jaenisch<br />

USA<br />

Professor of Biology<br />

Whitehead <strong>Institute</strong> and Dept. of Biology, MIT,<br />

Cambridge<br />

Prof. Stuart Forbes<br />

UK<br />

Centre for Inflammation Research,<br />

Queen’s Medical Res. Ins., Edinburgh<br />

Prof. Richard A. Young<br />

USA<br />

Professor of Biology Member, Whitehead <strong>Institute</strong>,<br />

Yale University<br />

Prof. Sir Ian Wilmut<br />

UK<br />

Centre for Regenerative Medicine,<br />

University of Edinburgh,<br />

Prof. Ahmed Mansouri<br />

Germany<br />

Investigator Max-Planck <strong>Institute</strong>,<br />

Molecular Cell Biology, Gottingen,<br />

Prof. Oscar K. Lee<br />

Taipei<br />

<strong>Institute</strong> of Clinical Medicine, National Yang-Ming<br />

University and Taipei Veterans<br />

Prof. Marius Wernig<br />

U.S.A.<br />

<strong>Institute</strong> for Stem Cell Biology and Regenerative<br />

Medicine, Stanford University<br />

Prof. Gerlinde Wernig<br />

U.S.A.<br />

Pathology Dept. & <strong>Institute</strong> for Regenerative Med.<br />

& Stem Cell Res., Stanford University<br />

Prof. Tobias Cantz Germany Hanover Medical School, Hanover<br />

Prof. Alan Mackay-Sim<br />

Australia<br />

Director, National Centre for Adult Stem Cell<br />

Research, Griffith University<br />

Prof. Miodrag Stojkovic<br />

Spain<br />

Deputy Director of regenerative medicine, Prince<br />

Felipe Research Centre, Valencia,<br />

Prof. Heiner Niemann<br />

Germany<br />

Institut für Tierzucht und Tierverhalten (FAL),<br />

Mariensee,<br />

Prof. John Aplin UK The University of Manchester, Manchester<br />

Prof. Geraldine Hartshorne<br />

UK<br />

Clinical Sciences Research <strong>Institute</strong>, University of<br />

Warwick<br />

Prof. L. Frith UK University of Liverpool,<br />

Prof. Petr Svoboda<br />

Czech Republic<br />

Department of Epigenetic Regulations, <strong>Institute</strong> of<br />

Molecular Genetics , Prague<br />

Prof. Vardhman K Rakyan<br />

UK<br />

Centre for Diabetes, Barts and The London<br />

School of Medicine and Dentistry, London<br />

Prof. Jean Bernard Dubuisson Switzerland<br />

Department of Obstetrics & Gynecology, Faculty<br />

of Medicine, Geneve University,<br />

Prof. Aleksandr A. Popov<br />

Russia<br />

Chief of the Endoscopic Surgery Department,<br />

Moscow<br />

Prof. Jan. Brosens<br />

UK<br />

Imperial College London/Hammersmith Campus,<br />

London<br />

Prof. Enlan Xia Republic of China<br />

Professor and Tutor of Master’s degree at Fuxing<br />

Hospital , Beijing<br />

About IRAN<br />

Shahr-e Sūkhté (Persian: ‏,شهرسوخته meaning<br />

“Burnt City”), also spelled as Shahr-e Sukhteh and<br />

Shahr-i Shōkhta, is an archaeological site of a sizable<br />

Bronze Age urban settlement, associated with the<br />

Jiroft culture. It is located in Sistan and Baluchistan<br />

Province, the southeastern part of Iran, on the bank<br />

of the Helmand River, near the Zahedan-Zabol road.<br />

A proposal is submitted to include it in the World<br />

Heritage List of UNESCO.<br />

Site<br />

Covering an area of 151 hectares, Shahr-i Sokhta<br />

was one of the world’s largest cities at the dawn of<br />

the urban era. The settlement appeared around 3200<br />

BCE. The city had four stages of civilization and was<br />

burnt down three times before being abandoned in<br />

2100 BCE. The site was discovered in 1967 and has<br />

been continually excavated since the 1970s by Iranian<br />

and Italian archaeological teams; new discoveries are<br />

reported from time to time.


Finds<br />

In December 2006, archaeologists discovered the<br />

world’s earliest artificial eyeball. It has a hemispherical<br />

form and a diameter of just over 2.5 cm (1 inch). It<br />

consists of very light material, probably bitumen<br />

paste. The surface of the artificial eye is covered<br />

with a thin layer of gold, engraved with a central<br />

circle (representing the iris) and gold lines patterned<br />

like sun rays. The female remains found with the<br />

artificial eye was 1.82 m tall (6 feet), much taller than<br />

ordinary women of her time. On both sides of the eye<br />

are drilled tiny holes, through which a golden thread<br />

could hold the eyeball in place. Since microscopic<br />

research has shown that the eye socket showed<br />

clear imprints of the golden thread, the eyeball must<br />

have been worn during her lifetime. The woman’s<br />

skeleton has been dated to between 2900 and 2800<br />

BCE. The oldest known backgammon, dice and<br />

caraway seeds, together with numerous metallurgical<br />

finds (e.g. slag and crucible pieces), are among the<br />

finds which have been unearthed by archaeological<br />

excavations from this site. Other objects found at the<br />

site include a human skull which indicates the practice<br />

of brain surgery and an earthen goblet depicting what<br />

archeologists consider to be the first animation.<br />

The ancient courier<br />

In one of the most recent discoveries from January, a<br />

team of Iranian and British anthropologists, working<br />

on human remains in the city from the 3rd millennium<br />

BC, identified a male camel rider who they believe<br />

was a messenger in ancient times.<br />

Studies of the skeletal remains belonging to the man<br />

reveal evidence of bone trauma, suggesting that he<br />

was a professional rider who most likely spent most of<br />

his life on camel back.<br />

Indications of riding are seen on the right leg bone<br />

of the man, who died at the age of 40 to 45. The<br />

swellings show that he continuously worked as a<br />

professional rider since he was a teenager. There are<br />

blade-shaped swellings on the lower part of the leg<br />

bone which indicate that he used to gather up his right<br />

leg while riding, suggesting that he rode on a large<br />

animal like a camel or ox. Although there is evidence<br />

showing that smaller draft animals were also used<br />

in the Burnt City, the act of gathering up a leg while<br />

riding is something that one does while riding a camel<br />

over long distances. Scientists, then, believe that the<br />

man was probably a courier who traveled regularly on<br />

camelback.<br />

Women’s role<br />

Some paleoanthropologists believe that mothers in the<br />

Burnt City had social and financial prominence. 5000<br />

year-old insignias, made of river pebbles and believed<br />

to belong only to distinguished inhabitants of the city,<br />

were found in the graves of some female citizens.<br />

Some believe the female owners of the insignias<br />

used them to place their seal on valuable documents.<br />

Others believe the owners may have used the seal to<br />

indicate their lofty status in society.<br />

Craftsmanship<br />

Paleopathological studies on 40 teeth unearthed in<br />

the Burnt City’s cemetery show that the inhabitants of<br />

the city used their teeth as a tool for weaving to make<br />

baskets and other handmade products.<br />

“More than 40 teeth lesions have been identified, the<br />

most prominent of which belongs to a young woman<br />

who used her teeth as a tool for weaving baskets and<br />

similar products,” said Farzad Forouzanfar, director<br />

of the Anthropology Department of Iran’s Archeology<br />

Research Center and head of the anthropology team<br />

at the Burnt City in an interview with CHN. The use of<br />

teeth as a tool in the Burnt City is seen in both males<br />

and females of different age groups. Evidence shows<br />

that weaving was more than a hobby in the prehistoric<br />

city. It was one of the most common professions in the<br />

city which required a special skill. Residents made a<br />

variety of woven products such as carpets, baskets,<br />

and other household items.<br />

http://en.wikipedia.org/wiki/Burnt_City<br />

Science News<br />

Stem Cells Made From Developing<br />

Sperm<br />

ScienceDaily (Aug. 7, 2009) — The promise of stem<br />

cell therapy may lie in uncovering how adult cells revert<br />

back into a primordial, stem cell state, whose fate is<br />

yet to be determined. <strong>No</strong>w, cell scientists at the Johns<br />

Hopkins University School of Medicine have identified<br />

key molecular players responsible for this reversion in<br />

fruit fly sperm cells. Reporting online in Cell Stem Cell,<br />

researchers show that two proteins are responsible<br />

redirecting cells on the way to becoming sperm back<br />

to stem cells.<br />

“We knew from our previous work that cells destined<br />

to be sperm could revert back to being stem cells, but<br />

we didn’t know how,” says Erika Matunis, Ph.D., an<br />

associate professor of cell biology at the Johns Hopkins<br />

University School of Medicine. “Since, dedifferentiation<br />

is an interesting phenomenon probably occurring in<br />

a lot of different stem cell populations, we wanted to<br />

know more about the process.”<br />

Like all stem cells, each of the nine stem cells in the<br />

fly testis divides to form two daughter cells: One stays<br />

a stem cell and the other differentiates into an adult<br />

cell, in this case, a sperm cell. To figure out what<br />

might cause sperm cells to revert or dedifferentiate,<br />

Matunis’s research team genetically altered the flies<br />

so that both cells become sperm, reducing the stem<br />

cell population in the testis to nothing.<br />

About a week later, the team examined these fly testes<br />

and found that the stem cells had been repopulated.<br />

To figure out how this was happening, the researchers<br />

first suspected two proteins—Jak and STAT—known<br />

to act together to help stem cells maintain their stem<br />

cell-ness. The team genetically altered flies to reduce<br />

the activity of Jak and STAT in the testis. Counting<br />

the number of cells, they found that the loss of Jak-<br />

STAT caused fewer cells to revert to stem cells; only<br />

60 percent of testes regained stem cells compared to<br />

97 percent in normal Jak-STAT-containing testes.<br />

“We now know that in the fly testis, interfering with<br />

Jak-STAT signaling interferes with the process of<br />

dedifferentiation,” says Matunis.<br />

Next, Matunis would like to figure out how Jak and<br />

STAT control dedifferentiation. “We don’t know if a cell<br />

4


is just reversing all of the steps to go back to being<br />

a stem cell or if it is doing something totally new and<br />

different, but we’re eager to find out,” she says.<br />

Authors on the paper are X. Rebecca Sheng and<br />

Erika Matunis of Johns Hopkins and Crista Brawley,<br />

formerly of Johns Hopkins, now at the University of<br />

Chicago.<br />

http://www.sciencedaily.com/<br />

releases/2009/08/090806<strong>12</strong>1716.htm<br />

D-81369 Munich<br />

www.interplan.de<br />

Phone: +49 (0)89 / 54 82 34 73<br />

Fax: +49 (0)89 / 54 82 34 42<br />

Board of Directors: Bruno Lichtinger, Dr. Markus<br />

Preußner, Dan Rivil, Avi Rosner<br />

Commerical Register: Jurisdiction: Munich,<br />

Registration Number: HRB 134 892<br />

www.IFFS<strong>2010</strong>.com<br />

5<br />

http://www.bentham.org/open/<br />

toanatj/index.htm<br />

The Open Anatomy Journal<br />

ISSN: 1877-6094<br />

Editor-in-Chief: Eimei Sato (Japan)<br />

Associate Editor: Guido Macchiarelli (Italy)<br />

Regional Editor (Europe): Stefania A. <strong>No</strong>ttola<br />

(Italy)<br />

11th Congress of the European<br />

Society of Contraception and<br />

Reproductive Health<br />

May 19-22, <strong>2010</strong><br />

The Hague, NETHERLANDS<br />

11 th<br />

ROYAN<br />

International Research Award<br />

Sep 15 -17, <strong>2010</strong><br />

IFFS Munich <strong>2010</strong> - YES YOU CAN!!<br />

IFFS is proud that in <strong>2010</strong> we celebrate 60 years as<br />

the world´s leading organization devoted to human<br />

fertility and infertility.<br />

Made up of 59 international fertility societies IFFS<br />

standardizes and classifies fertility and infertility<br />

processes all over the world<br />

Come join us in Munich on September <strong>12</strong>-16 for our<br />

20th World<br />

Congress!<br />

IFFS is you: write your abstract now and join us in<br />

Munich.<br />

YES YOU CAN !!<br />

Professor David Healy<br />

Key <strong>No</strong>te Lecture: Safety issues in hormonal therapy<br />

Tuesday 14th September, Alfred O. Mueck, Germany<br />

Congress, Meeting & Event Management AG<br />

Albert-Rosshaupter-Strasse 65<br />

Reproductive Biomedicine<br />

& Stem Cells<br />

Biology & Technology<br />

Deadline 10 April 2008<br />

E-mail: Info@<strong>Royan</strong><strong>Institute</strong>.org

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