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Freezers at the Royan Institute & Cell Tech Pharmed

In recent years, the regenerative medicine and cell therapy industry has witnessed significant progress in different aspects of science, technology and commercialisation. The Cell Tech Pharmed pilot site in Iran is the first authorised stem cell manufacturing centre with a 3,000 patient capacity and is the largest stem cell manufacturing site in the Middle East.

A recent documentary on Iranian TV, IRIB, showed Dr. Nasser Aghdami as he reported on the process and progress of cell therapy technology in Iran. Dr. Aghdami was the head of regenerative medicine and cell therapy in the renowned Royan institute. Several years of research there led to his use of fundamental science in clinical areas via clinical trials; the application of this science is advancing in Iran.

Dr. Aghdami is now CEO of the Cell Tech Pharmed company, established in 2014 to meet the increasing demand for stem cell therapy. The product development focus is on five major and distinct areas - systemic diseases with an underlying inflammatory and immunologic etiology which can be addressed by intravenous delivery of cell therapy for immuno-modulation; cardiac and vascular diseases where cell therapy products are being developed for both local and systemic application; orthopaedic diseases of the knee, ankle and pelvis where cell therapy products can be locally administered to potentially repair the damaged joint cartilage or generate new bone; improving outcomes of bone marrow transplantations associated with oncology or genetic conditions and lastly skin augmentation, where current methods are ineffective. Scientific support comes from co-founders of the new company, The Royan Institute and the Barakat Pharmed Company.

In the Royan Institute, research activities at the Department of Regenerative Medicine focus on similar areas with translational and clinical studies.  GMP and Quality Control for cell production, as well as isolation and culturing cells in completely sterile conditions, is of major importance in the exacting efforts to produce cells with the highest quality for cell therapy. The Royan Institute has had a number of Planer freezers over the years - and the latest, supplied by our distributor Iran Panam Company, are shown here.

For further details, please visit the following websites
Iran Panam
Cell Tech Pharmed
Royan Institute
Kryo 560



Society for Low Temperature Biology meeting

The 2017 Society for Low Temperature Biology meeting will be taking place at the Aurora, British Antarctic Survey, Cambridge, UK on the 19th and 20th September 2017.

The Society for Low Temperature Biology (SLTB) was founded in 1964 with the purpose of promoting research into the effects of low temperatures on all types of organisms and their constituent cells, tissues and organs. Such studies have applications in diverse scientific fields, from biology and medicine to engineering, conservation and environmental science.

The interests of its members are diverse, however, all share a common interest in understanding relationships between low temperatures and biological systems. The objectives of the SLTB are:

  • To advance the education of the public in the science of low temperature biology.  
  • To advance the science of low temperature biology. 
  • To promote research into the science of low temperature biology and; 
  • Disseminate the useful results to the public.

Interests range from natural mechanisms of cold tolerance, the cryopreservation of cells and tissues for medical, agricultural and conservation purposes, low temperature microscopy, through to the physics and physical chemistry of water and ice; and heat and mass transfer in all types of biological systems.

As a pioneering company within this field Planer will be attending this meeting to demonstrate our latest Cryogenic equipment.

For further information about this meeting please visit

Meta analysis on ovarian tissue freezing

On 17th July Science Daily reported on a new study published in Reproductive Sciences. Ovarian tissue freezing, a procedure where ovarian tissue is removed and frozen cryogenically for later use, has been considered experimental until now. The new study, (SAGE Publications 13 July 2017), reports that nearly four out of 10 women who underwent the procedure were able to have children later in life as a result.

Despite progress over the past two decades, "the procedure still remained in the experimental realm," say the authors Drs Pacheco and Oktay. "Given these recent data, ovarian tissue cryopreservation should be considered as a viable option for fertility preservation." Dr. Kutluk Oktay, who performed the world's first procedure of this kind in 1999, together with co-author Dr. Fernanda Pacheco examined data from 1999 to 2016. They found that 309 ovarian tissue freezing procedures resulted in 84 births and 8 pregnancies that lasted beyond the first trimester. The procedure restored reproductive functions and reversed menopause in nearly two out of three women including either a resumed menstrual cycle, ovarian follicular growth, or natural fertility and the procedure restored natural fertility in great majority of the cases: while two thirds could conceive naturally only about one third needed IVF.

"The procedure is superior to egg freezing as it can also reverse menopause and restore natural fertility," continued the senior study author Dr. Oktay. "The next frontier is to explore the procedure's potential in delaying childbearing among health women, not just cancer patients." The authors note that "In all OTTs resulting in LBs, the tissues had been frozen with the slow freezing technique".

We at Planer have been extensively involved in this new area - see the web news section of our website for details of births where our Kryo 360 has helped the process.

Further information
Science Daily:
Full article


AVA Clinic, Latvia, chooses Planer benchtop incubator

Riga, in Latvia, is one of the most beautiful cities in Europe and is the third biggest city in the Baltic region, right after St. Petersburg and Stockholm. The AVA Clinic based there, is part of a European network of infertility treatment clinics founded in 1993 and this one opened in 2005.

The experienced Riga team get high infertility treatment results, and they adhere strictly to ISO 9001:2008 which is why they chose the Planer Origio BT37 benchtop incubator. The BT37, a worldwide success story, is a high accuracy bench-top incubator for growing and maintaining gametes and embryos. The incubator will keep cells at optimal temperature, humidity and gas content by maintaining a constant and clean environment and it has extremely accurate temperature control, systems for pH stability and regulated humidity. All the technology goes to making sure that an embryo suffers little or no exposure to temperature or pH level changes.



Improve post-thaw function in cryopreserved Mesenchymal Stromal Cells

Results from a multi disciplinary study into improving post thaw function in MSCs has just been published in the journal Stem Cells and Development. Current methods for freezing mesenchymal stromal cells (MSCs) result in poor post-thaw function, which limits the clinical utility of these cells. The investigation, carried out by Pollock, Samsonraj et al with Professor Allison Hubel, (pictured here), a Mayo Clinic and University of Minnesota collaboration, developed a novel approach to preserving MSCs using combinations of sugars, sugar alcohols, and small-molecule additives. MSCs frozen using these solutions exhibit improved post-thaw attachment and a more normal alignment of the actin cytoskeleton compared to cells exposed to dimethylsulfoxide (DMSO). As a part of the protocol the team used a Planer controlled rate freezer with a six part programme starting at -20oC  with differing rates cooling down to -100oC before transferring to liquid nitrogen. The authors point out that rapid cooling and warming steps in their freezing profile correspond to a temperature spike which is included in the freezing ramps to reliably induce extracellular ice formation in the samples before they undercool substantially - which can result in undesirable intracellular ice formation when nucleation does finally occur.

Osteogenic and chondrogenic differentiation assays showed that cells retained their mesenchymal lineage properties and genomic analysis indicated that the different freezing media evaluated had  different effects on the levels of DNA hydroxymethylation, which are a principal epigenetic mark. RNA sequencing and quantitative real time-polymerase chain reaction validation demonstrated that transcripts for distinct classes of cytoprotective genes, as well as genes related to extracellular matrix structure and growth factor/receptor signaling are upregulated in experimental freezing solutions compared to DMSO. The studies validate the concept that DMSO-free solutions can improve post-thaw biological functions and are viable alternatives for freezing MSCs. These novel solutions promote expression of cytoprotective genes, modulate the CpG epigenome, and retain the differentiation ability of MSCs, suggesting that osmolyte-based freezing solutions may provide a new paradigm for therapeutic cell preservation.

For further information:-
Improved Post-Thaw Function and Epigenetic Changes in Mesenchymal Stromal Cells Cryopreserved Using Multicomponent Osmolyte Solutions

Allison Hubel, PhD Department of Mechanical Engineering University of Minnesota 
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Andre J. van Wijnen, PhD Department of Orthopedic Surgery Mayo Clinic,  
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Planer controlled rate freezer - kryo 560

40 years of Planer Incubators

Planer incubator 1980It's the tenth anniversary of our first concept for the BT37 benchtop incubator, which is now known around the world.  But it is not the only incubator we make. Or have made. While we are known for our controlled rate freezers, few people remember our first incubator - way back in 1976!

Looking through the archives we found a photo of one we used to sell 40 years ago. We collaborated with the then UK Department of Health and Social Services in the production of a new form of anaerobic incubator as an alternative to the prevailing jar system for the isolation of anaerobes from clinical material.  The machine - shown here - was built around 1980 and was tested by a team led by a Dr Berry from the Department of Microbiology at St. Thomas's Hospital Medical School London. It was distributed for a while by Gallenkamp who became part of Fisons Scientific plc.

With several thousand sold, the precision benchtop BT37, pictured here, has proved a boon to both the IVF industry and researchers in other fields. It was introduced in 2009 and is now found in labs and clinics in each continent of the world. With or without humidity control its market leading temperature control is also making it increasingly useful in transgenic and animal ART as well as the huge success it is in the human fertility market.

However we have not stopped innovating or developing new products. With bench space in labs at a premium we will be showcasing a new, unique incubator at ESHRE 2017 in Geneva. It is designed for the modern laboratory and has the capability of market leading volume of dish spaces in a unique small footprint.

A unique modular approach (patents pending) allows users to add units as space and throughput require and units will fit in most laboratory hoods helping to improve work flow whilst reducing the risk of mishap during transfer for inspection. And all this whilst maintaining the legendary temperature control accuracy throughout the chamber environment. Details of this innovative incubator will be available on our website, from July once the product is launched.

Find out more


Round-up of interesting ISBER 2017 abstracts

The International Society for Biological and Environmental Repositories (ISBER) is an international forum that addresses the technical, legal, ethical, and managerial issues relevant to repositories of biological and environmental specimens. This year's Annual Meeting took place in Toronto Canada - here is a round of abstracts that we felt might be of interest:-

The Effect of Liquid Nitrogen Storage on ctDNA Extraction from Plasma
ISBER abstract reference BRS-8 
Kenney1, J. Sosa-Baez2, E. Lin1, E. Hernandez1, P. McNeil1, C. Mariano1, L. Villafania2, J. Padilla2, A. Samoila2, E. Peerschke2, M. H. Roehrl1
1Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States,
2Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, United States

The identification of a biomarker for cancer that is procured in a safe, non-invasive, and efficient manner for the detection of disease has been made possible in recent years via the discovery of cell-free circulating tumor DNA (ctDNA). The full scope of potential for the uses of ctDNA have not yet been realized; therefore, there is a call to preserve valuable samples in the hope that these resources can be utilized with forthcoming technologies. Traditionally, either due to cost or ease of use, tissue samples are stored at −80°C where they can be kept for many years, whereas in LN2, they can potentially be preserved indefinitely without degradation of the sample for future genetic and proteomic applications. Currently, plasma samples taken for ctDNA extraction are routinely stored at −80°C for extended periods of time. The trend toward banking samples in LN2, however, presents the question of whether the quality ctDNA in plasma samples stored in LN2 will be suitable for assays in the future. It has been shown that LN2 preserves many elements of the plasma, such as antibodies/proteins; however, the ability to preserve ctDNA has not yet been tested.

Methods and Results 
ctDNA from standard plasma samples stored at room temperature, −4°C, −80°C, and in vapor phase LN2 (−180°C) over various amounts of time (days to months) was extracted in a Hamilton easyBlood robot and ctDNA yields were compared.

Storing quality control plasma standards at −80°C produces a mean concentration of ctDNA of 0.95 ng/μl. We stored aliquots of a parallel standard in LN2 for 2 weeks and were able to extract a ctDNA concentration of 1.019 ng/μl. Additional data will be presented at the meeting. Initial results indicate that plasma storage in LN2 is at least not inferior, if not superior, to storage at −80°C. Storage at temperatures higher than −80°C is not recommended and further data will be acquired to study how time-sensitive cfDNA is with respect to “needle-to-freezer” speed and handling.

 We aim to provide evidence that ctDNA extracted from plasma stored in LN2 for various amounts of time will have equal to or better yields of ctDNA than plasma stored at other temperatures. Encouraged by the results, we plan to test more samples at varying temperatures, optimal and suboptimal, for extended periods of time in order to discover the ideal long term storage conditions for plasma used for ctDNA extraction.

Impact of Room Temperature on Tissue Quality as Assessed by RNA Integrity Number (RIN)
ISBER abstract reference HSR-12 
Bhanot1, C. Lai1, M. Santin1, C. Mariano1, P. McNeil1, M. R. Weiser2, M. H. Roehrl1
1Pathology, MSKCC, New York, New York, United States
2Surgery, MSKCC, New York, New York, United States

The practice of oncology is being propelled by new emerging technologies in genomics, transcriptomics, and proteomics to help better understand molecular events that result in tumor initiation, development, and progression. However, the results of genomic, transcriptomic, and proteomic analysis can reflect true alterations only when biospecimens used are of very high quality. Therefore, the impact of pre-analytic variables on tissue quality needs to be studied, as this will help identify areas for improvement in biobanking protocols.

Due to high volume and engagement of biobank personnel in various operations in a busy cancer center, it is not always possible to transfer the tissue in to liquid nitrogen immediately upon receipt. We are studying the impact of transport/storage at room temperature on fresh tissue kept at room temperature (RT) for various time points.

Tissues aliquots from the same patient (tumor and normal) were divided and frozen immediately in vapor phase liquid nitrogen or kept at room temperature (20°C) for various amounts of time (0-24 hours) before freezing. Total RNA was extracted from tissues using RNeasy Mini Kit (Qiagen) and RNA analysis was performed on the Agilent Bioanalyzer.

Initial data show that the quality of tissue as determined by RNA integrity numbers (RIN) is best maintained when the tissue is transferred to liquid nitrogen immediately upon arrival. When the tissue is transferred to liquid nitrogen immediately on arrival, tissues yielded RIN values close to 10 (optimal). When kept at RT for short time intervals, i.e., up to 1 hour, the RIN values are relatively unchanged. However, when the transfer of tissues into liquid nitrogen was delayed and the tissue is kept at RT for longer than 2 hours, a decline in the RIN scores was observed. Interestingly, we noticed that RIN values are typically higher in tumor vs. normal tissues from the same patient.

Any modern biorepository needs to closely monitor its protocols and implement an ongoing internal as well as external quality improvement plan that will help identify areas for improvement to better maintain the integrity of banked tissues.

Assessing the Quality of RNA from Fresh Frozen Human Tumour Tissues Stored Long-Term at Cryogenic Temperatures
ISBER Abstract Reference RS-15 
Kelly1, M. de Ladurantaye2, M. Albert1, M. Moore3, S. Dokun4, J. Bartlett1,5
1Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, Ontario, Canada,
2Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada,
3Ontario Health Study, Ontario Institute for Cancer Research, Toronto, Ontario, Canada,
4Health Services Research, Ontario Institute for Cancer Research, Toronto, Ontario, Canada,
5Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada

It is widely recognized that the integrity of tissue specimens preserved at temperatures below the glass state is stable long-term. Scientific studies in literature, however, do not generally extend beyond a few years. With biobanks reaching a degree of maturity where specimens may be stored for over a decade, this assumption should be tested to provide the data to support extended long-term storage and demonstrate continued fit-for-purpose. Since its inception in 2004, the Ontario Tumour Bank (OTB) has had an ongoing commitment to quality and, in accordance with biobanking best practices, has embedded stringent quality control (QC) and quality assurance (QA) measures into its routine procedures. One such measure, triggered twice annually, includes the random selection of cryopreserved tissues to undergo external quality assessment (EXTQA) by a third party to measure the integrity of the tissue's DNA and RNA. Here, as an extension of OTB's routine EXTQA, we analyzed second aliquots of previously evaluated tissues collected between 2005 and 2014 to determine if RNA integrity is affected by extended long-term storage in liquid nitrogen vapor phase.

RNA was extracted from duplicate aliquots of 70 cryopreserved tissue samples across 11 disease sites previously analyzed in prior years during routine EXTQA and having recorded RNA integrity number (RIN) scores of 7.5 or greater. Extractions and quality determinations were performed at the Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) according to CTRNet SOPs. RNA quality was determined by the RIN assigned by the Agilent Bioanalyzer.

The results of external quality assurance 1 (EXTQA1) and external quality assurance 2 (EXTQA2) for RNA extracted from fresh frozen tissues were compared; 94% of EXTQA2 samples were Acceptable to Very Good in quality. There was no significant correlation (r = 0.10, p = 0.80) between the quality of RNA extracted in EXTQA2 and storage time. There was also no significant correlation (r = 0.04, p = 0.92) between the change in RIN score between EXTQA1 and EXTQA2 and storage time.

These data suggest that extended long-term storage of tumor tissue samples in vapor phase does not negatively affect the quality of RNA derivatives. From this, we conclude that OTB samples banked since inception continue to be viable for downstream applications and are fit to be used in high-impact cancer research studies.

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ESHRE 2017

The European Society for Reproduction and Embryology (ESHRE) will be holding their annual conference in the beautiful city of Geneva, Switzerland this year from the 2nd to the 5th July.

On Sunday 2nd July, there will be fifteen special interest group pre-congress presentations, before the main programme itself starts on Monday 3rd July.

Planer will be exhibiting once again at ESHRE, with some exciting new products. Don't forget to come and see us on stand D16 to find out more.

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