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Agenda

Full-day Events with Awesome Speakers

Webinar Schedule

Day 1 full schedule

November 11, 2021 @ 10:00 - 16:25

Retinal cell replacement in macular degeneration: A pluripotent stem cell-based approach

Rajarshi Pal

Rajarshi Pal

Chief Scientist

Centre for Cellular and Molecular Platforms (C-CAMP), NCBS-TIFR Campus

Eyestem Research, India

ABSTRACT

Dysfunction or death of retinal pigment epithelial (RPE) cells is involved in age-related macular degeneration (AMD) and some forms of Retinitis Pigmentosa. Since there is no cure for most patients affected by these diseases, transplantation of RPE cells derived from human induced pluripotent stem cells (hiPSCs) represents an attractive therapeutic alternative. First attempts to transplant hiPSC-RPE cells in AMD and Stargardt patients demonstrated the safety and suggested the potential efficacy of this strategy. At Eyestem, we have successfully generated retinal pigment epithelial (RPE) cells from clinical grade hiPSCs employing a novel cGMP compliant protocol and performed in depth characterization of the differentiated cells with respect to identity, purity and potency. We then tested the safety and efficacy in RNU immune suppressed rats and RCS rat model of retinal degeneration post sub-retinal transplantation of Eyecyte-RPE. I will present these data sets and share our experience on this unique journey of taking a pluripotent stem cell-based product from the bench to the clinic.

Characterization and ageing study of sequentially passaged Wharton’s jelly derived Mesenchymal stem cells (WJ-MSCs)

Urvi Panwar

Urvi Panwar

PhD research Scholar

Amity University of Rajasthan

India

ABSTRACT

In recent scenario, mesenchymal stem cells (MSCs) are regarded as a highly prospective tool in regenerative medicine due to their properties of self-renewal, multi-lineage differentiation, immunoregulation and immunomodulation. Before using for clinical purpose, their characterization and validation is essential. Moreover, the satisfactory quantity of MSCs for clinical requirement demands ex-vivo expansion of MSCs. The in-vitro multiplication leads them to replicative senescence which may alter their genetic stability. Hence, the present study has focused on characterization and ageing study of Wharton’s jelly derived MSCs primarily extracted from human umbilical cord tissues. The WJ-MSCs were sequentially passaged up to 14th passage (P14) and the cells were evaluated at interval of P2, P6, P10 and P14. WJ-MSCs were evaluated for their morphology, surface markers, stemness markers, tumorigenicity, ageing, DNA damage, chromosomal aberration and telomere length. For the examination, five full term (n=5) delivered human umbilical cord samples were processed to obtain WJ-MSCs. At initial passages, morphological appearance of MSCs was small; fine spindle shaped which were transformed into flat, long and broader cells at later passages. The cell proliferation rate was gradually decreased after 10th Passage. WJ-MSCs have expressed stemness markers such as OCT-4 and NANOG genes; while they showed high expression of MSC surface markers CD90 and CD105; and lower expression of CD34 and CD45. WJ-MSCs were observed non- tumorigenic having slow cellular aging process during subsequent replication. Also, no chromosomal abnormality was monitored up to 14th passage while measured increase in comet score and decrease in telomere length was observed in later passages. Consequently, the study suggests that the early and middle passaged (i.e. less than P10) WJ-MSCs are of good quality applicants for clinical administration for treatment.

Lung Stem Cell Research to drug discovery

Manash K. Paul

Manash K. Paul

Assistant Project

University of California, USA

USA

ABSTRACT

Lung diseases are among the leading causes of morbidity and mortality worldwide, and in India according to the World Health Organization. Lung studies remain an unmet and urgent medical need and a critical area of research, especially in India. The tracheobronchial epithelium serves as the first line of defense of the airway and is constantly exposed to environmental hazards and oxidative stress-mediated injury. Thus, a tightly controlled mechanism of repair by resident airway basal stem cells (ABSC) is required to maintain airway health. Defects in the repair process result in debilitating lung diseases. Harnessing this reparative ability to avoid or cure the debilitating effects of pathologic lung remodeling is one potential technique for lung disease management. I will discuss my study on the cellular and molecular mechanisms that control lung stem/progenitor cell populations during injury repair and lung pathogenesis. In an exciting study, we investigated the dynamic interactions between airway basal stem cells and their signaling niches regulating homeostasis, injury, and aging. This study also led to discovering a novel phosphorylation of β[1]catenin protein at tyrosine 489 and its strong association with ABSC proliferation. To identify small molecules that could potentially restore dysregulated homeostasis, we discovered a Wnt/β[1]catenin inhibitor WIC1 through high-throughput drug screening. WIC1 may serve as a tool compound in regenerative medicine studies with implications for restoring normal airway homeostasis after injury. Further, we were the first to employ stem cells to create a three[1]dimensional (3D) lung-in-a-dish. It will be feasible to examine the biological underpinnings of lung disorders, construct human-specific disease modeling, drug screening, toxicity studies, and future therapeutics using our 3D organoid technology.

Pluripotency Stem Cells (iPSCs): The Future Possible Strategies Use For Overcoming Difficulties in Cancer Therapies

Neelotpala Dash

Neelotpala Dash

Student

KIIT University

India

ABSTRACT

Stem Cell and Regenerative Medicine is one of the most emerging branches of Medical Sciences deals with therestoration oftissueororgans for patients suffering from chronic diseases. Stemcells can be categorized as Embryonic Stem Cells and Adult Stem Cells. In 2006, Takahashi & Yamanaka reprogrammed somatic cells to form embryonic-like stem cells which have similar properties to Embryonic Stem Cells. They designated these cells as Induced Pluripotency Stem Cells (iPSCs). In 2012, this work was awarded the Nobel Prize to John Gurdon, USA and Shinya Yamanaka from Japan. iPSCs are capable of theoretically generating cells from any origin i.e. endodermal, mesodermal and ectodermal. Since their discovery, they have contributed to the study and treatment of various diseases such as Huntington's disease, Parkinson's disease, down-syndrome and several others including cancer which is one of these rare diseases that needs more attention. Today’s talk mainly involves the use of iPSCs cells in the application of various strategies for curing cancer. There are two possible major strategies where iPSCs can be used to replace or repair tissue of cancer patients which are damaged due to radiation or chemotherapies. iPSCs derived from other healthy tissue of the same patients could be used to regenerate those tissues damaged by the tumour themselves or subsequent treatment. The second area in which patients specific iPSCs may offer a distinct advantage for cancer immunotherapy is by using functional active T-cells generated by using patients iPSCs cells. With recent development in Nobel prize-winning genome editing technology such as CRISPR-cas9, it becomes easier for scientists to develop iPSCs cells more easily for this future program in cancer therapeutics. Overall it shows that iPSCs may be useful in overcoming difficulties in future therapies of cancer will be discussed in this talk.

Organoids: A Revolutionary New Tool for Drug Screening

Rekha Pal

Rekha Pal

Director Scientific Engagement

Director Scientific Engagement Crown Bioscience Inc, USA

Engagement, Crown Bioscience Inc. , USA

ABSTRACT

“The poor translatability of early-stage preclinical models is a major setback in oncology drug development. Immortalized cell lines, that are extensively used in drug screens, undergo genetic drift over time due to adapting to in vitro growth, thus showing limited relevance to the human disease. Interpatient tumor heterogeneity is also a major hurdle with standard in vitro models failing to recapitulate this variability. Patient-derived xenografts are the gold standard preclinical models for their proven translatability to the human disease but can be costly and time consuming to generate and maintain. The Hubrecht Organoid Technology (HUB) has pioneered the development of tumor organoids, a revolutionary patient-derived 3D in vitro system that recapitulates the genomic, morphological, and pathophysiological characteristics of their parental tumor. HUB organoids provide highly clinically relevant 3D in vitro models for oncology drug development. To overcome the limitation imposed by sourcing patient material for organoid preclinical development PDX can be used as a source of human tumor tissue leading to a patient-relevant matched in vitro/in vivo platform for oncology drug screening.” 

Learning bullets:

  • Discover organoids as a more physiologically relevant 3D in vitro model
  • Find out why HUB organoids are considered best in class systems
  • Understand how organoids are revolutionizing oncology drug development
  • Learn about how patient-derived xenografts (PDX) can be leveraged to develop the largest organoid library for oncology drug discovery

Cancer Stem Cells : Major Cell Type Responsible for Promotion, Progression and Development of Drug Resistant in Metastatic Cancer

 Pravin D. Potdar

Pravin D. Potdar

Former Head

Jaslok Hospital & Research Centre

Jaslok Hospital & Research Centre, India

ABSTRACT

Even though there are many strategies and innovations are developed  in cancer therapeutics, the latest  updated Globocan 2020 has reported  new estimates on the global cancer burden which has risen to 19.3 million cases with 10 million cancer deaths in 2020.The main reasons for the failure of cancer treatment are metastasis, recurrence, heterogeneity, resistance to chemotherapy and radiotherapy. All these failures can be explained by studying the involvement of Cancer Stem Cells (CSCs) which are responsible for developing multidrug resistant to cancer therapy causing cancer metastasis and relapse. Therefore, it is mandatory to study the  CSCs and their phenotypes to get the most promising targeted therapy for cancer. Cancer Stem Cells were first identified from Acute Myeloid  Leukaemia by Lapidot team and  published  in Nature  journal in 1994.  CSCs  have shown to express different surface markers which are responsible for promotion, progression & malignant transformation in nonsolid and solid tumour. Lapidot has clearly  shown that  the injection of these initiated Cancer Stem Cells  into animal  developed tumours  which clearly indicates the malignant phenotypes of these cells. Cancer Stem Cells have self-renewal and differentiation properties and give rise to multiple cellular subtypes. The activities of CSCs are controlled by many intracellular and extracellular signalling pathways which are the major drug targets for cancer therapy and need more attention. My lab has also identified initiated Cancer Stem Cells from non-metastatic breast cancer patient and characterised for the molecular profiling for various genes involved in pluripotency, progression and promotion of metastatic potential of breast cancer. This study clearly indicates the heterogeneity of breast cancer stem cells responsible for metastasis and relapse of this disease even after specific targeted therapy. Therefore to understand the exact nature of CSCs,  several scientists are working in view to study the molecular characteristics and regulation of these Cancer Stem Cells to find out  the solution to target these cells for cancer therapy both in basic research as well as in clinical studies. My talk will mainly emphasise on the importance of Targeting  Cancer  Stem Cells and their signalling pathways for getting  better targeted therapy to cure cancer without relapse.

Cartilage specific Bioink for 3D printing of human ear pinna

Meghnad G Joshi

Meghnad G Joshi

Associate Professor

Department of Stem cells and Regenerative medicine, D.Y. Patil University

India

ABSTRACT

Auricular deformities (Microtia) can cause physical, social as well as psychological impacts on a patient’s wellbeing. Currently available surgical techniques and transplantation methods have many limitations that can be overcome with the help of 3D bioprinting technology. Printable bioink enriched with cartilage-specific extracellular matrix (ECM) synthesis was done by digesting xenogeneic pinna cartilage and polymerized by adding polymers. Viscosity and Fourier-transform infrared spectroscopy were used for the characterization of bioink to get desired viscosity and polymerization. Human ear pinna was 3D printed using extrusion technique and CAD, STL software which facilitated the automated printing in relatively less time without continuous monitoring. Thermal degradation of pinna was checked by thermal gravimetric analysis. Biodegradability and swelling of ear pinna were observed for understanding the nature of pinna and the impact of external factors. 3D printed pinna biocompatibility was proved by in ovo and in vivo studies. In vivo biocompatibility of the 3D printed pinna showed demonstrable recellularization. Ultrasound sonography as well as Computerized tomography (CT) of 3D printed pinna given the normal thickness after transplantation in rat. Histology and SEM analysis revealed the recellularization of cartilage-specific cells and the development of ECM in 3D printed ear pinna after transplantation. 3D printed ear pinna provided ideal results for tensile properties such as elasticity. Chondrocyte specific progenitor cells express CD 90+ which highlighted newly developed chondrocytes in both the grafts which indicated that the xenograft was accepted by the rat. Transplantation of 3D ear pinna was successful in an animal model and can be utilized as tissue engineered ear bank.

Stem cell & Regenerative Medicine in Gynaecological Disorders

Prabhu Chandra Mishra

Prabhu Chandra Mishra

President

International Association of Stem Cell and Regenerative Medicine

India

ABSTRACT

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Stem Cell: A Journey into Innovative Frontiers

Laila M. Montaser

Laila M. Montaser

Professor

University of Menoufia

Egypt

ABSTRACT

In recent years we have witnessed major breakthroughs in stem cell research at all levels. Stem cells are characterized by a unique ability to self-renew and differentiate and have revolutionized modern biological sciences and medical research with unique approaches for understanding developmental processes and disease modeling. Stem cells can be used for regenerative medicine and as treatments for disease. The application of tissue engineering related transplantation, stem cells, and local changes in the microenvironment is expected to solve major medical problems. Recent advances in regenerative medicine have confirmed the potential to manufacture viable and effective tissue engineering 3D constructs comprising living cells for tissue repair and augmentation. 3D bioprinting has emerged as a promising new approach for fabricating complex biological constructs. Cell printing aims to deliver living cells in a 3D fashion to recapitulate stem cell niches and pathological tissue morphologies for drug screening, or to mimic human tissue complexity working as biologically relevant substitutes. Flexible 3D tissue engineering technology enables stem cells generated from an individual’s own body to divide after printing and differentiate in a way to form and replace any tissue type of the body. With recent advances in 3D cell culture technology, stem cells are allowed to reside in culture environments emancipating their intrinsic self-organizing properties and form into organoids  resembling structural as well as functional characteristics of organs, serving as an ideal platform for studying pathological states and performing drug screens. The recent development of 3D printing technology empowers the opportunities of developing bio functional complex tissue substitutes via layer-by-layer fabrication of cell(s), biomaterial(s), and bioactive compound(s) in precision and the concept of in situ 3D bioprinting in the lab to cut out the middle step of in vitro growing cells and just implanting cells directly into the body for growth.

 

Role of Adipose Tissue-Derived Stem Cells versus Differentiated Schwann-like cells Transplantation on the Regeneration of Crushed Sciatic Nerve in Rats. A Histological Study

Sahar M.M.Omar

Sahar M.M.Omar

Professor

Ain Shams University and Armed Forces College of Medicine

Egypt

ABSTRACT

Background & objectives: Despite surgical advances, recovery of peripheral nerve injuries has often been poor, leading to irreversible impairment. This study aimed to differentiate adipose-derived stem cells (ASCs) into Schwann-like cells (SCs) in vitro and assess their role versus the undifferentiated ASCs in the regeneration of crushed sciatic nerves in adult male albino rats.

Materials & Methods: We performed a simple and less costly method to differentiate ASCs into SCs. Forty rats, weighing 200-250 g, were randomly divided to 4 equal groups. Group I (control) subjected to sham operation. Group II subjected to crush injury of the sciatic nerve. Group III subjected to crush injury with local transplantation of ASCs. Group IV subjected to crush injury with local transplantation of differentiated Schwann-like cells. The rats were sacrificed 4 weeks later. We studied the nerves using H&E and Masson’s Trichrome stain. Immuno-histochemical studies using S-100 and neurofilament-H (NF-H), together with morphometric and statistical studies were done.

Results: Differentiated Schwann-like cells adopted a spindle-like morphology and 87.9% of the cells became GFAP positive and 90.4% were positive to S-100. Group II showed thin discontinuous nerve fibers with proliferation of SCs. Significant increase in collagen area percentage, and significant decrease in S-100 & NF-H immune reaction was noted as well. Group IV revealed better regeneration of axons, and higher intensity of immune reaction by S-100& NF-H, than Group III. Meanwhile, both Groups III & IV showed thicker, more packed nerve fibers with significant decrease in collagen area percentage compared to Group II.

Conclusion: Our results suggested that differentiated Schwann-like cells might have a more beneficial role than ASCs, for treatment of peripheral nerve injuries.