Hossein Baharvand Ph.D.
Department of Stem Cells and Developmental Biology
Professor of Stem Cells and Developmental Biology
Hossein Baharvand is a distinguished Professor of Royan Institute, where he firstly joined in 1995. He received his B.Sc. in Biology from Shiraz University in 1994, and M.Sc. in Developmental Biology from Shahid Beheshti University, Tehran in 1996. He received his Ph.D. in Cell and Developmental Biology from Khwarizmi University (formerly Tarbiat Moallem University) in 2004. In 2012, he became Professor at Royan institute. He is also appointed as the head of department of Developmental Biology at University of Science and Culture (2006-jan 2018). For the first time, he generated the mouse and human embryonic stem cells (2003) and induced pluripotent stem cells (2008) in Iran. This has enabled his team to pursue many avenues of research into translational research and regenerative medicine.
He is the founder and director of Royan Institute for Stem Cell Biology and Technology, where the institute is committed to cross-disciplinary partnerships and collaborations by biology, engineering, and medical academics to improve human health and life quality. Now, the institute includes 4 main departments named as Stem Cells and Developmental Biology, Regenerative Medicine, Cell Engineering and the newly established Brain and Cognitive Sciences.
He has given numerous tutorials and invited talks in many congresses. He is the editor of four international books which were published by Springer (2010 and 2012) and John Wiley, USA (2015). He has published 322 international and 102 national peer-reviewed papers, as well as seven chapters in international books, seven books in Persian, and eight translated English text books into Persian. Eight figures of his peer-reviewed publications were selected as cover pages of international journals. As of March. 2018, Google Scholar reports over 8000 citations and h-index 45 to his work. He is currently the editorial board member of eight international journals (e.g., Journal of Biological Chemistry and Nature Scientific Reports).
He has focused his research interests on improving the translational research and regenerative medicine mainly through the understanding of Stem Cells and Developmental Biology and Biologically inspired Engineering.
Given the rapid pace of developments within the pluripotent stem cell field, it is likely that the generation of safe and effective derivatives for use in cell therapy will be achieved in the near future. These cells also provide fascinating possibilities for the study of disease models, tissue engineering, drug discovery and developmental biology.
He has been working on pluripotency mechanism and germ cell biology and differentiation into cardiomyocytes, neural cells and hepatocytes in cross-disciplinary collaborations by biology, engineering, and medical researchers. He has also been making numerous contributions to clinical trials and tissue-specific stem cell transplantation, as well as developing cell manufacturing.
In order to develop and define molecular mechanisms of pluripotency, he has already introduced the acquisition of naïve pluripotency in mice and men by modulating TGFβ signaling pathway as two sides of the same coin. They found a new chemically defined culture medium, called R2i (two inhibitors) in the presence of inhibitors of TGFβ and FGF signaling pathways exhibiting typical features of ground state pluripotency. R2i allows for efficient pluripotent stem cell generation from mouse and rat preimplantation blastocysts as well as from primordial germ cells (PGCs). R2i as same as the well-known 2i condition which include the FGF and GSK3 inhibitors could support the criteria of ground state pluripotency. High throughput transcriptome analysis indicated that in spite of the high similarity between 2i and R2i grown ESCs, BMP4 signaling pathway is highlighted in R2i cells. Our miRNome analysis indicated a distinct set of ‘‘ground-state miRNAs’’ encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Moreover, the proteome analysis revealed focal adhesion signaling pathway signiﬁcantly downregulated and glycolysis signaling pathway upregulated in ground state conditions. Their time course transcriptome analysis during ESC generation from inner cell mass in R2i regimen indicated that DNA methyltransferases and epithelial to mesenchymal transition blockage play pivotal roles in launching the ESC self-renewal program. In contrast to the mouse context, however, it seems that TGFβ signaling plays a stimulatory role in generation and maintenance of human naïve pluripotency.
B) Neural cell differentiation
He also successfully produced neual stem cells and neural cells from the pluripotent stem cells. He and his team have developed animal models to evaluate the function of produced neural cells. They showed improvement of cognitive function in Alzheimer’s, better recovery in spinal cord injury, slight restoration in retinal injury and improvement in optic nerve injury. He also provided a proteomic view of the molecular mechanisms of Multiple Sclerosis recovery after ESC-derived neural stem cell transplantation in animal model. He reported the first established long-term self-renewable and multipotent neural stem cells through direct conversion of human fibroblasts by a single zinc-finger transcription factor. In addition, his work has resulted in efficient production of human retinal pigmented epithelial cells from normal and retinal disease iPSCs.
C) Cardiomyocyte differentiation
He produced matured cardiomyocytes from ESCs by the cardiac fibroblast-derived ECM (cardiogel). Next, he described human cardiomyocyte differentiation using protein transduction by Islet1 recombinant protein or gene overexpression by Fndc5 or direct conversion of fibroblasts into cardiomyocytes. In a step towards regenerative medicine technologies, they developed a scalable and robust differentiation platform to scale up cardiomyocytes to help repair damaged heart. By integrating tissue engineering, he improved the biological function of decellularized heart valves generation and production of humanized rat heart constructs by protein tethering and three-dimensional cell seeding in a bioreactor using human ESCs-derived cardiac progenitor cells.
D) Hepatocyte differentiation
He and his team also differentiated human ESCs, to hepatocytes in two- and three-dimenstional culture systems. Their research also led to generating liver disease-specific iPSCs that were efficiently differentiated into functional hepatocyte-like cells. They also first introduced a scalable stirred-suspension bioreactor culture of functional hepatocyte-like cells. In the next step, he improved the protocol and developed a cost-effective method for producing human hepatic cells from size-controlled pluripotent stem cell aggregates. He has generated hepatocyte-like cells in an efficient method of sustained and localized delivery of growth factors using microparticles, which engineer a better three-dimensional microenvironment for cell differentiation. Using these stem cell-derived hepatocyte-like cells, their secreted molecules and/or extracellular vesicles derived from them, they improved acute or cirrhosis animal models of liver injury.
E) Germ cells
The opinion that female mammals have lost the capacity for oocyte production after birth has been challenged recently by the discovery of proliferative germ cells in adult mouse and human ovaries. However, the existence of oogonial stem cells (OSCs) in postnatal mammalian ovaries is still controversial. He and his team isolated mitotically active functional germ cells from adult mouse and human ovaries by ovarian organoids (ovaroids) formation. This innovative approach represented an efficient, yet simple and reproducible method for isolation and expansion of functional germ cells, which would have profound implications for basic research into oogenesis and translation of this work to the clinical setting. Additionally, he and his team are interested in spermatogonial stem cells isolation, expansion and charachterization and understanding of signalling pathways.
The full list of publications can be find here: https://www.ncbi.nlm.nih.gov/pubmed/?term=Hossein+Baharvand
- Sarah Rajabi, Sara Pahlavan, Mohammad Kazemi Ashtiani, Hassan Ansari, Saeed Abbasalizadeh, Forough Azam Sayahpour, Fahimeh Varzideh, Sawa Kostin, Nasser Aghdami, Thomas Braun, Hossein Baharvand*. Human embryonic stem cell-derived cardiovascular progenitor cells efficiently colonize in bFGF-tethered natural matrix to construct contracting humanized rat hearts. Biomaterials, 2018;154:99-112. This study provides a robust platform for generation of artificial humanheart by an engineering approach and resolves major bottlenecks hindering further development of this technology.
- Zeinab Heidariyan, Mohammad Hossein Ghanian, Mohsen Ashjari, Zahra Farzaneh, Mostafa Najarasl, Mehran Rezaei Larijani, Abbas Piryaei, Massoud Vosough, Hossein Baharvand*. Efficient and Cost-effective Generation of Hepatocyte-like Cells Through Microparticle-mediated Delivery of Growth Factors in a 3D Culture of Human Pluripotent Stem Cells. 2018;159:174-188. This article offers a novel approach towards scalable technologies for hepatocytic differentiation and engineering a better 3Dmicroenvironment for cells.
- Mehdi Totonchi#, Seyedeh-Nafiseh Hassani#, Ali Sharifi-Zarchi#, Natalia Tapia, Kenjiro Adachi, Julia Arand, Boris Greber, Davood Sabour, Marcos J. Araúzo-Bravo, Jörn Walter, Mohammad Pakzad, Hamid Gourabi, Hans R. Schöler, Hossein Baharvand*. Blockage of the Epithelial-to-Mesenchymal Transition Is Required for Embryonic Stem Cell Derivation. Stem Cell Reports. 2017, 2017;9(4):1275-1290. This article, for the first time provides a time course transcriptional resource highlighting the dynamics of the gene regulatory network during the Inner Cell Mass to ESC transition.
- Sharif Moradi, Ali Sharifi-Zarchi, Amirhossein Ahmadi, Sepideh Mollamohammadi, Alexander Stubenvoll, Stefan Günther, Ghasem Hosseini Salekdeh, Sassan Asgari, Thomas Braun*, Hossein Baharvand*. Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground State Pluripotency. Stem Cell Reports. 2017, ;9(6):2081-2096. Here, it is demonstrated that ground-statepluripotency is associated with a unique miRNA signature, which supports ground-state self-renewal by suppressing differentiation.
- Ebrahim Shahbazi, Sharif Moradi, Shiva Nemati, Leila Satarian, Mohsen Basiri, Hamid Gourabi, Narges Zare Mehrjardi, Patrick Günther, Angelika Lampert, Kristian Händler, Fulya Hatay, Diana Schmidt, Marek Molcanyi, Jürgen Hescheler, Joachim L. Schultze, Tomo Šarić*, Hossein Baharvand*. Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor. Stem Cell Reports. 2016,;6(4):539-551. This study reports that a singlezinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent neural stem cells, which holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases.
- Hananeh Fonoudi#, Hassan Ansari#, Saeed Abbasalizadeh, Mehran Rezaei Larijani, Sahar Kiani, Shiva Hashemizadeh, Ali Sharifi Zarchi, Alexis Bosman, Gillian M. Blue, Sara Pahlavan, Matthew Perry, Yishay Orr, Yaroslav Mayorchak, Jamie Vandenberg, Mahmoud Talkhabi, David S. Winlaw, Richard P. Harvey, Nasser Aghdami, Hossein Baharvand*. A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes from Pluripotent Stem Cells. Stem Cells Translational Medicine. 2015;4(12):1482-1494.. #: co-first author. (Top downloaded paper). This universaland robust bioprocessing platform can provide sufficient numbers of human PSC-cardiomyocytes for regenerative medicine technologies to rescue, replace, and help repair damaged heart tissues and for developing advanced biologics and drugs for regeneration of lost heart tissue using high-throughput technologies.
- Seyedeh-Nafiseh Hassani, Mehdi Totonchi, Ali Sharifi-Zarchi, Sepideh Mollamohammadi, Mohammad Pakzad, Sharif Moradi, Azam Samadian, Najmehsadat Masoudi, Shahab Mirshahvaladi, Ali Farrokhi, Boris Greber, Marcos J. Araúzo-Bravo, Davood Sabour, Mehdi Sadeghi, Ghasem Hosseini Salekdeh, Hamid Gourabi, Hans R. Schöler, Hossein Baharvand*. Inhibition of TGFß Signaling Promotes Ground State Pluripotency. Stem Cell Reviews and Reports. 2014;10(1):16-30. Here, a novel defined approach was introduced to efficiently establish the groundstate
- Shiva Akbari-Birgani, Saman Hosseinkhani*, Sepideh Mollamohammadi, Hossein Baharvand*. Delay in Apoptosome Formation Attenuates Apoptosis in Cardiac Differentiation of Mouse Embryonic Stem Cells. Journal of Biological Chemistry. 2014, 289(24):16905-16913. This study for the first time shows how ESCs could differentiate two processes of apoptosis and differentiation from each other.
- Massoud Vosough, Eskandar Omidinia, Mahdi Kadivar, Mohammad-Ali Shokrgozar, Behshad Pournasr, Nasser Aghdami, Hossein Baharvand*. Generation of Functional Hepatocyte-like Cells from Human Pluripotent Stem Cells in a Scalable Suspension Stem Cells and Development, 2013; 22: 2693-705. This amenable scaling up and outlined enrichment strategy provides a new platform for generating functionalhepatocyte-like cells which may facilitate biomedical applications of the human PSC-derived hepatocytes. The editor of journal has written a commentary on this paper.
- Azadeh Zahabi, Ebrahim Shahbazi, Hamid Ahmadieh, Seyedeh-Nafiseh Hassani,Mehdi Totonchi, Adeleh Taei, Najmehsadat Masoudi, Marzieh Ebrahimi, Nasser Aghdami, Ali Seifinejad, Faramarz Mehrnejad, Narsis Daftarian, Ghasem Hosseini Salekdeh, Hossein Baharvand*. A New Efficient Protocol for Directed Differentiation of Retinal Pigmented Epithelial Cells from Normal and Retinal Disease induced Pluripotent Stem Cells. Stem Cells and Development, 2012, 21(12):2262-72. Here, they introduced a highly efficient approach in differentiation of ESC and iPSC into retinal pigmented epithelium. Also, it has been shown that retinal disease-specific human iPSCs offer an unprecedented opportunity to recapitulate normal and pathologic formation of human retinal cells in vitro, thereby enabling pharmaceutical screening, and potentially autologous cell replacement therapies for retinal diseases.
- Arefeh Ghodsizadeh, Adeleh Taei, Mehdi Totonchi, Ali Seifinejad, Hamid Gourabi, Behshad Pournasr, Nasser Aghdami, Reza Malekzadeh, Navid Almadani, Ghasem Hosseini Salekdeh, Hossein Baharvand*. Generation of Liver Disease-Specific Induced Pluripotent Stem Cells along with Efficient Differentiation to Functional Hepatocyte-Like Cells. Stem cells reviews and Reports. 2010 6(4):622-32. Here, for the first time, the authors provide proof of principal that human liver-disease specific iPSCs present an exciting potential venue toward cell-based therapeutics, drug metabolism, and human liver development and disease models for liver failure disorders.
- Baharvand H*, Kazemi Ashtiani S, Taee A, Massumi M, Valojerdi MR, Eftekhari Yazdi P, Zarei Moradi Sh, Farrokhi A. Generation of New Human Embryonic Stem Cell Lines with Diploid and Triploid Karyotypes. Development, Growth and Differentiation, 2006, 48, 117-128. This article reports the derivation and characterization of five human ESC lineswith diploid and triploid karyotypes.
He has received 29 international and national awards including 10th (2004), 12th (2006), and 17th (2012) annual Razi research award on medical science hosted by Iran Ministry of Health and Medical Education, 26th Khwarizmi International Award (2013), hosted by Iran Ministry of Science, Research and Technology, 27th annual book of the year of the Islamic republic of Iran (2010), Academy of Medical Sciences of Iran (Dr. Hadavi’s Award in 2010, 2014), International Prof. Yalda Award for Excellence in Medical Sciences (2015), distinguished scientist in Iranian Biotechnology (2015) and Genetics (2016) national award. He is the winner of the Islamic Educational, Scientific, and Cultural Organization (ISESCO) Prize for research in the field of Biology (2010). Moreover, he was introduced as Prominent Professor in 3rd term of Allameh Tabatabaei’s Award hosted by Iran vice Presidency for Science and Technology, Presidency and National Elite Foundation (2014). He is the winner of the United Nations Educational, Scientific and Cultural Organization (UNESCO)-Equatorial Guinea international prize (2014) for research in life sciences aimed at improving the quality of human life with his stem cell research and its numerous applications in regenerative medicine. He was also selected as 20 stem cell person of the year 2017 award nominees hosted by THE NICHE site (https://ipscell.com/2017/11/20-stem-cell-person-of-the-year-2017-award-nominees/).
Moreover, as of now three companies are spinned off from the work he inititated at the Royan Intitute for Stem Cell Biology and Tehcnology including Cell Tech Pharmed as a cell factory for cell therapy, Royan Biotech for production of recombinant proteins, and Royan Stem Cell Technology for banking of cord blood stem cells.
Furthermore, he has had several efforts in publicizing the stem cell biology in Iran and in this regard he with his team established a lab entitled “Stem Cells for all” and a “mobile advanture lab” by an equipted bus. The aim of these participatory teaching and learning methods is to motivate and empower learners to acquire the knowledge, skills, attitudes and values necessary to shape a sustainable future for stem cells and their potentials in regenerative medicine. He has also established “annual international summer school” program since 2010. The participants were trained by invited speakers from abroad to incease international and national interactions and training methods in this field.
His hobbies are Karate (with Black belt grade, Dan 1), Mountaineering and study of historical stories.