We have developed a new technique for direct isolation of human placenta stromal cells from tissues of fetal origin (fPSC) by a unique process which allows the direct migration of the desired cells from tissue fragments to culture dishes for further expansion. The resultant selected placental stromal cell population was found to indirectly enhance the regeneration of failing bone marrow and to mitigate of acute radiation syndrome (ARS) following total body irradiation. IM treatment by fPSC showed that these stromal cells were more immunocompetent and could reside longer in the injected muscle with no apparent adverse effects associated with IV delivery of MSC of different origin. In studies on mitigation of radiation effects these cells enabled to repopulate the failing bone marrow lineages with subsequent regeneration of the peripheral blood cells. This saved the treated animals from the lethal effects of ARS with dramatic significant raise of the survival in ~8Gy irradiated mice from less than a third to almost 100% with a fast recovery of the bone marrow and the peripheral blood cell lineages. Detailed cytokines analyses showed that the injected xenogeneic cells respond to the stress of the high dose irradiation by the secretion of a wide range of related pro-regenerative cytokines and growth factors including GM-CSF, GCSF, IL-6, GRO, MCP-1, all associated with the regeneration of the hematopoietic systems and other regenerative processes. The IM based fPSC treatments have also been investigated as cell therapy for bone marrow failure due to different other causes. Other indications are tested for the PSC treatment, to help the regeneration of various tissues and organs affected by autoimmune diseases. These include inflammatory bowel disease (IBD) and autoimmune inflammatory processes in the brain, such as an EAE model of multiple sclerosis. Further detailed studies are in progress to better understand the indirect mechanism of action of the PSC by stress induced activation of relevant family of genes.
Prof. Raphael Gorodetsky is the head of the Laboratory of Biotechnology and Radiobiology at the Sharett Institute of Oncology, Hadassah - Hebrew University Medical Center in Jerusalem, where he is employed as a faculty m ember since 1989) affiliated to the Hebrew University Medical School in Jerusalem). He received his M.Sc. and PH.D from the Hebrew University in 1985 and had his Post Doc at UCLA Medical Center (1985-1988). Among other subjects he was involved in cancer research and studies in radiobiology associated with regenerative medicine. Earlier studies were associated with trace elements physiology in health and disease. Later directions of his research focused mainly on the invention of fibrin based biomaterials used for tissue regeneration and cell therapies and on different aspects of cancer research and radiation biology. Among the new ventures he co-founded was Hapto Biotech in 2000, where he served as the chief scientist (later merged with Ortec to form Forticel International, NY, in 2007). In this area he designed fibrin based matrices for tissue regeneration, specifically of bone and cartilage In recent years Prof. Gorodetsky was mainly involved in the development of cell based treatment for regenerative medicine and tumor control purposes, including the mitigation of radiation effects. Some of these findings were already applied clinically by Pluristem Therapeutics for clinical use. In parallel Prof. Gorodetsky is involved in the development of new anticancer immunotherapies. Besides authoring more than 100 peer reviewed scientific publications and chapters, he edited and authored the book “Stem cells and Tissue Repair” in 2010 (by the Royal Society of Chemistry RSC, Cambridge, UK). He served as secretary of Israel Stem Cells Society (2014-2017) and has been a member in a number of related national and international societies. The laboratory is collaboration with a number of Research Centers in Israel and abroad, including UCLA - Los Angeles, NIH - Bethesda, Cherite - Berlin, Pluristem - Haifa.
Mesenchymal stem cells (MSCs) are a major stem cells source for cellular therapy, used in clinical applications for almost a decade. The “gold rush” to use MSCs in clinical trials is because they possess self-renewal ability, multilineage differentiation, immunomodulaory properties; easy isolation, ex-vivo expansion in-vitro1. Miniaturized incubator for transportation of sample biopsy would promote in maintaining cellular viability. Adult sources of MSCs: stroma of bone-marrow, adipose /dental tissue and peripheral blood. Currently, there are more than 400 registered clinical trials aimed at evaluating potential of MSC-based cell therapy. Extensive ex-vivo expansion of MSCs are prone to lose their therapeutic potential because of changes in cellular organization. Bone-marrow MSCs exert strong therapeutic effect in treating bone disorders, neurological disorders viz., Multiple Sclerosis, Encephalomyelitis, Amyotrophic Lateral Sclerosis, Motor Neuron diseases, Progressive Supranuclear Palsy, Parkinsons, Spinal Injury 2,3,4,5. Dental matrix, pulp and follicle tissue derived MSCs have osteoconductive, osteoinductive potential in pulp regeneration. Intravenous injection of MSCs has shown to effectively suppress induction of peripheral immunomodulation1.
Dr. Basan Gowda S Kurkalli, Professor at Nitte University Center for Stem Cell Research and Regenerative Medicine (NUCSReM), India. Stem cell expert member for Institutional Committee for Stem Cell Research for NUCSReM, Yenopoya University and Innov4sight. Thirty years of basic and applied clinical research experience globally, as Senior Scientist at GIOSTAR, India; Investigator in-charge at Cognate Bioservices Ltd. Israel and Clinical Assistant Professor at Amrita Center for Nanoscience and Molecular Medicine. Postdoctoral fellow and Doctoral student from Hadassah-Hebrew University, Israel. Published 13 research articles, one book chapter, five international issued patents and guided two M.tech students and one Ph.D
Skeletal (also known as stromal or mesenchymal stem cells (MSCs) are undifferentiated cells that have the capability of self‐renewal and multilineage differentiation including osteoblasts and adipocytes. MSCs has been an attractive candidate to be used in regenerative medicine protocols for tissue regeneration. However, the cellular heterogeneity of MSCs with respect to their differentiation potential considered as a challenge for their use in regenerative medicine. Moreover, the absence of specific surface marker such as Cluster of Differentiation (CD) for these cells cannot distinguish stem cell populations from other progenitor cells or possible contaminating cells in culture. Thus, the current work is subjected to study the possible use of CD markers identified by quantitative proteomic analysis to isolate and characterize homogenous populations of either human MSCs or their descendent progeny based on flow cytometryic (FACS) analysis and cell sorting. To achieve this goals, it has been important to develop cell dissociation methods to obtain single cell suspsions at different time points of MSCs culture and to ensure that the dissociated cells maintained their biological functions. So that, a number of cell dissociation techniques were tested including enzymatic methods such as trypsin/EDTA and non-enzymatic methods like cell dissociation buffer beside the use of phosphate buffered saline without calcium or magnesium (PBS-/-). Time of incubation need to achieve single cell suspension, cell viability based on the trypan blue dye exclusion test and flow cytometry were used to evaluate the results of the different methods in this comparative study. The results showed that using PBS-/- and trypsin/EDTA is the optimal method to dissociate the cells during differentiation without significant loss of surface markers expression.
Dr. Asma AL-Shammary has completed her PhD from Clinical Institute at Odene University Hospital-University of Southern Denmark, Denmark in the field of Regenerative Medicine and Stem Cells Biology. She is working as assistant proffessor at the University of Hail. Moreover, she has published one article in the area of stem cells CD markers in reputed journal and book chapter in Recent advances in stem cells, from basic research to clinical applicaion
Stem cells can self-renew and produce different cell types, thus providing new strategies to Repair, Regenerate and Restore (3R’s) missing tissues through regenerative dentistry. Adult mesenchymal stem cells have been identiﬁed in several oral and maxillofacial tissues suggesting that oral tissues are a rich source of stem cells, of which Dental Pulp Stem Cells (DPSCs) derived from neural crest cells and neuroectodermal in origin. DPSCs are positive for markers such as CD29, CD44, CD73, CD90 Stro 1 and CD105, and are negative for CD34 and CD45. They also express the transcription factors, such as OCT-4 and NANOG, which are implicated in the maintenance of pluripotency. There are several studies which are being done using DPSCs to study the biologic properties like proliferation rate, population doubling time and differentiation potential. Human teeth is made of enamel, dentin, and cementum, and a highly mineralized extracellular matrix. Tooth enamel made of 96% inorganic material and 4% organic material, and dentine is made of 70% inorganic material. The organic matrix of tooth consists of collagen, non-collagenous proteins, and lipids, of which 85–90% of the total protein consists of type I collagen, growth factors like BMPs belonging to TGF beta family. In our study we are evaluating the combination of demineralized and/or mineralized teeth matrix obtained from the discarded teeth with DPSC’s following tissue engineering strategy towards osteoconduction /induction of hematopoietic microenvironment, potentiating towards osteogenic/odontogenic differentiation resulting in repair, regenerate and restoration of craniofacial tissues following extraction of tooth for orthodontic indications
Mr. Chethan Kumar obtained my Master’s degree in Biotechnology, from Mangaluru University, Karnataka, India. Currently pursuing my Doctoral Degree under the guidance of Dr. Basan Gowda S. Kurkalli, Nitte University Center for Stem Cell Research & Regenerative Medicine (NUCSReM), K.S. Hegde Medical Academy (KSHEMA), Mangaluru, Karnataka 575018, India.I Did a short term project/dissertation entitled “protein targeted therapy for human glioblastoma cells” at Yenepoya University, Mangaluru, India.I worked on urinary tract infection in children and pregnant woman against E. coli and S. Aureus. I have extensive experience in Cell Culture, Immunology, Microbiology Techniques, Genetic Engineering and Molecular Biology assays
Fecal continence is primarily maintained by the internal anal sphincter (IAS). Loss of IAS integrity or functionality leads to passive fecal incontinence.Our previous studies have shown restoration of fecal continence in rabbits following implantation of engineered autologous IAS Biosphincters for up to 3 months.Objective:Here, we studied a longerfollow up (12 months)of restoration of fecal continenceusing IAS Biosphincters. Methods:Fecal incontinence was induced in rabbits as described before. Rabbits were assigned to 3 groups: (i) non-treated group (n=4), (ii) treated group (n=7) that received implantation of Biosphincters and (iii) sham group (n=5). Anorectal manometry (resting pressure and RectoAnal Inhibitory Reflex, RAIR) was followed regularly for up to 12 months. Histological and pathological analyses were performed. Results:Incontinence in rabbits was evident by their lack of fecal hygiene and by significant reduction in resting pressure and RAIR (26±7 mmHg and 19±6%) compared to baseline (38±2 mmHg and 62±5%). Resting pressures and RAIR were restored and maintainedin the treated group (32±3 mmHg and 63±6%)and were significantly higher than those in the non-treated group at 12 months. Resting pressures and RAIR were not significantly different between non-treated and sham groups. Conclusion: This study provides a promising tissue engineering and regenerative medicine approach to treat passive fecal incontinence using engineered Biosphincters. Our long term follow up study (12 months) indicated the sustainedlong-term effect of Biosphincters implantation on restoration of continence.
Khalil N Bitar PhD, AGAF Professor of Regenerative Medicine, Gastroenterology and Physiology & Pharmacology Professor, Core Faculty Member, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences Director of Gastroenterology Programs Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine Richard H. Dean Biomedical Research Building, Room 257 391 Technology Way
In cell therapy, tissue regeneration ability of stem cells relies on the paracrine effects between stem cells and recipient cells. Our recent studies demonstrated that, in tissue engineering, bioactive silicates could stimulate paracrine effects between stem cells and recipient cells, which enhanced tissue generation. Therefore, we proposed that, in cell therapy, it may be an effective method to improve tissue regeneration ability of stem cells through activating the paracrine effects between stem cells and recipient cells with bioactive silicates. As urine-derived stem cells (USCs) have been injected for wound healing and bioglass (BG) have shown bioactivity for various types of stem cells, in this study, we activated USCs with effective BG ionic products. Then, the conditioned medium of BG-activated USCs were used to culture endothelial cells and fibroblasts as well as co-cultures of endothelial cells and fibroblasts. Results showed that growth factor expression in BG-activated USCs was upregulated. In addition, paracrine effects between USCs and recipient cells in wound healing were stimulated, which resulted in enhanced capillary-like network formation of endothelial cells and matrix protein production as well as myofibroblast differentiation of fibroblasts. Finally, the BG-activated USCs were applied on fullthickness excisional wounds. Results confirmed that BG-activated USCs had better wound healing ability through improving angiogenesis and collagen deposition in wound sites as compared to USCs without any treatment. Taken together, BG can be used to promote wound healing ability of USCs by enhancing paracrine effects between USCs and recipient cells.
Haiyan Li has completed her PhD at the age of 28 years from Chinese Academy of Science and postdoctoral studies from Monash University in Australia and INSERM U1026 in Frnace. She is now an assocaite professor in School of Biomedical Engineering, Shanghai Jiao Tong University, a top 3 University in China. She has published more than 60 papers in reputed journals and 2 book chapters.
In Alzheimer disease (AD) patients, amyloid β (Aβ) peptide-mediated degeneration of cholinergic system utilizing acetylcholine (ACh) for memory acquisition is observed. Since AD therapy using acetylcholinesterase (AChE) inhibitors are only palliative for memory deficits without reversing disease progress, there is a need for effective therapies, and cell-based therapeutic approaches should fulfill this requirement. In order to recover cognitive function and to eliminate the causative Aβ peptide, we established F3.ChAT human neural stem cells (NSCs) encoding choline acetyltransferase (ChAT) gene (an ACh-synthesizing enzyme) as well as HMO6.NEP human microglial cells encoding neprilysin (NEP) gene (an Aβ-degrading enzyme) and HMO6.SRA cells encoding scavenger receptor (SRA) gene (an Aβ-uptaking enzyme). The cells (2 ⅹ105 cells) were transplanted intracerebroventrocularly to mice showing memory loss induced by challenge with cholinotoxin AF64A, and brain Aβ accumulation, ACh concentration, and cognitive function were analyzed. Transplanted NSCs (F3.ChAT) and microglial cells (HMO6.NEP and HMO6.SRA) were found to survive up to 4 weeks in the mouse brain and expressed their functional genes. The NSCs and microglial cells encoding each functional gene restored the learning and memory function of AF64A-challenged mice by eliminating Aβ deposit and recovering ACh level, in which the effectswere further enhanced by combinational treatment with F3.ChAT and HMO6.NEP or HMO6.SRA cells. The cell therapy also attenuated inflammatory astrocytic (glial fibrillary acidic protein) response by reducing Aβ accumulation. Taken together, it is expected that NSCs and microglial cells over-expressing ChAT, NEP or SRA genes could be candidates for replacement cell therapy of Alzheimer disease.
Prof. Yun-Bae Kim has completed his PhD at the age of 33 years from Seoul National University, Korea, and has studied as a visiting professor at University of British Columbia, Canada. He is a professor of College of Veterinary Medicine, Chungbuk National University, Korea. He has published more than 300 papers in reputed journals and has been serving as an Editor-in-Chief of Laboratory Animal Research.
Dental implants are considered to be the best aesthetic treatment option (Gold Standard) since few decades. Methods of accelerating osseointegration are being considered by surface modifications ofTi implant surface. Titanium (Ti) metal as such being an inert bio-material just favors for cell attachment. On surface modifications/coating/acid etching the process of interaction between the implant surface and cells surrounding the bone will be improved. Apart from chemical modifications, with the use of tissue engineering technology biologically modified surfaces are being introduced, which include surface coating of Ti implants with stem cells before implant placement, or by wrapping the stem cell sheet on to the implant before placement. But Adult Stem cell therapy is very limited owing to the complexity of the tissue isolation procedure. In order to overcome this limitation, we are trying to utilize the dental stem cells isolated from the discarded tooth, for surface coating of the Ti implants. Particularly in this study we intend to validate and compare the osteogenic potential, dental stem cells derived from pulp and follicular tissues from discarded tooth and their in vitro interaction on surface modified titanium implant surface. This study thereby will help to identify the more potent dental stem cells with respect to the osteogenic potential, proliferation rate and adherent properties. These investigations will help topotentiate the use of allogenic dental stem cells at the implant site in future.
Dr. Sushmita V P obtained my Bachelor’sdegree, from Sri Ramakrishna Dental College, Coimbatore. Currently pursuing my Master’s degree under the guidance of Prof. Dr. Chethan Hegde at A.B.Shetty Memorial Institute of Dental Sciences Mangalore. Currently doing a basic implantolgy Course in the same institution. And also perusingmy dissertation titled “Comparison of Interaction Dental Pulp and Dental Follicular Stem Cells in Bone Regeneration on Titanium Implants” Co guided by Prof. (Dr.) Basan Gowda S. Kurkalli.And I have Presented Paper and posters in several national and state conferences.
Familial hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease affecting at least 1 in 500 people worldwide causing sudden cardiac death and heart failure. A leading cause of the HCM is mutations within sarcomeric genes, with myosin binding protein-C (MYBPC3) being the most common. Specifically, a mutation in MYBPC3 (termed MYBPC3ΔInt32) has been reported to affect almost 4% of South Asians. MYBPC3ΔInt32 variant results in the loss of 25bp within intron 32, leading to skipping of exon 33 at the transcriptional level and a truncated C-terminus of the protein at the translational level. MYBPC3ΔInt32 are known to be associated with HCM causing contractile dysfunction as demonstrated by the expression of cMyBP-CC10mut protein on cultured adult rat cardiomyocytes. Despite the high prevalence of this variant, the exact mechanisms in its potential for cardiac pathophysiology are still unknown. In this study, we investigate on studying the MYBPC3ΔInt32 variant from human subjects by exploiting the use of hiPSC cardiomyocytes (CM), an efficient tool being used to model HCM. Urine and peripheral blood samples were collected from human subjects with or without MYBPC3ΔInt32 and were processed to obtain the urinary progenitor cells and peripheral blood mononuclear cells. These cells were efficiently reprogrammed into iPSC using the nonintegrating viral approach and differentiated into contracting cardiomyocytes. Patient-specific iPSC-CM were able to recapitulate the hypertrophy phenotype at the cellular level by analyzing the cell size at the single-cell level. However, the predicted exon skipping mechanism wasn’t seen in patient-specific iPSC-CMs as demonstrated using human endocardial biopsies in earlier studies. Future studies will focus on maturing these iPSC-CMs to understand the exact molecular mechanisms of MYBPC3ΔInt32 at transcriptional level and at functional level by observing for the effect of contractile dysfunction via bio-physiological experiments. The results obtained from this study may deliver a substantial platform for personalized medicine and drug discovery to prevent the development of heart failure occurring worldwide.
The regeneration of articular cartilage is a great challenge. Stem cell-derived exosomes (SC-Exos) are nano-sized extracellular vesicles that contain various types of nucleic acids and proteins. Many researches have shown that SC-Exos showed similar therapeutic effect as their parent stem cells to promote tissue regeneration. However, cartilage regeneration often takes a relatively long time, and there is currently no effective method to durably retain exosomes at cartilage defect. In this study, SC-Exos was encapsulated into a photo-induced imine crosslinking (PIC) hydrogel glue which presents excellent operation ability, biocompatibility, and cartilage-integration to construct an acellular hydrogel tissue patch (EHG) for cartilage regeneration. Methods：Exosomes were extracted from iPS derived MSC by differential centrifugation. The EHG hydrogel tissue patch was prepared by mixing exosomes with hydrogel precursor solution following by 365 nm light irradiation. The dynamic rheology of EHG tissue patch under light irradiation was performed on HAAKE MARS III rheometer. In vitro release of exosomes from EHG tissue patch was tested using q-Nano particle analyzer. The full-thickness cartilage defects with diameter of 4 mm were made on the both hind legs of rabbits. And the defects were treated with in situ formed EHG hydrogel tissue patch. 12 weeks later, the regeneration of cartilage defects were evaluated by histological analysis. Results: Our results showed that EHG hydrogel tissue patch could be formed conveniently in 1 minute under 365 nm light irradiation. In vitro experiments showed that more than 90% exosomes were retained in hydrogel after 14 days. The results of in vivo experiments demonstrated that EHG hydrogel tissue patch could seamlessly and tightly attach to cartilage defect, and promote cell migration and proliferation in situ. The results of histological analysis showed that the cartilage defects site treated by EHG hydrogel tissue patch were filled with newly formed hyaline cartilage which integrated well with native cartilage. However, similar to the sham control group, the cartilage defects treated by one-time-injection of equal amount exosomes remained unhealed. Conclusion:We have developed an in situ formed acellular hydrogel tissue patch EHG through combining SC-Exos with PIC hydrogel glue for cartilage defect repair. It is found that the EHG hydrogel tissue patch can seamlessly attach with native cartilage and effectively retain exosomes at cartilage defect site, which finally led to integrative hyaline cartilage regeneration. Our SC-Exos encapsulating hydrogel glue tissue patch provides a novel cell-free material with great practical value for the extensive repair of tissues and organs.
The nanotechnology has concentrated to study by researchers around the world to synthesize novelty nanoparticles which will be used in wide range of applications from industry to medicine.In the recent years, one of the most common nanomaterial in the world is nanoparticles. In addition, Multifunctional nanoparticles has been growing by scientists around the world. The various metallic, ceramic and polymeric compounds like Iron Oxides, Zinc Oxides, Iron-Cobalt, Nickel- Cobalt, Titanium Dioxide, Ag doped gold, Copper alloys, PEG, PPA, PMMA, Chitosan, Hydroxyapatite and sort of that, will be produced by chemists, physicians or materialist in the laboratory. There are various method to synthesize the nanoparticles like precipitation, chemical and physical vapor deposition, thermal and plasma spray, laser deposition, mechanical alloying and so on. Because of an impressive and unique chemical, physical and an antimicrobial properties of nanoparticlesalong with their biocompatibility; makes these materials find specific applications in various industries. Thus, nanoparticles have lots of applicationsin manufacturing, agriculture, environment, energy, electronics, and medicine. These use as an industrial coatings, lubricant oils, catalysts,gas sensors, magnetic separators,antioxidant, break down oil, breakdown volatile organic air pollutants,fuel cell electrodes, storage materials, lithium ion batteries, semiconductor (photovoltaic cells), solar steam device, storing and packaging of agricultural produces, nutrientsabsorber, food flavoring, perfumes, scratch resistance eyeglasses, fluorescent biological labels, contrast imaging, bone growth, drug and gene delivery, immunoassay, bio detection of pathogens, separation and purification of biological molecules and cells, cancer diagnosis and treatment, tumors destruction via heat therapy (hyperthermia), tissue engineering and etc. So, propose of this paper is detecting the intelligent multifunctional materialsand evaluating wonderful characteristics which is be synthesized by various methods.
AmirsadeghRezazadehNochehdehi, I'm an Iranian Researcher. I'm visiting researcher atDepartment of Chemistry, Faculty of Science, agriculture, University of Zululand, KwaZulu-Natal, South Africa now. Besides, I'll be fellow researcher of Gdansk University of Technology, Gdansk, Poland, too. Once, I've fully worked on newest subject in the field of Materials, Advanced Materials, Biomaterials, Nano-Materials, Nano-Bio-Materials and Nanomedicine specially
Cancer is a complex disorder involving the perturbation of several different pathways that regulate cell proliferation, cell differentiation, cell survival and Autophagy. Autophagy is a key regulator in maintaining cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via degradation of damaged organelles and aggregated proteins. Recent studies have nailed the role of Autophagy in inducing cancer drug resistance through Cancer Stem Cells. However, persistent activation of Autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to apoptosis in Cancer Stem Cells. Therefore, inducing cell death through Autophagic induction could be an alternative therapeutical approach for cancer treatment. Recently, we have identified, Rottlerin, derived from a medicinal plant (Mallotus philippinensis) as a novel Autophagic inducer. Rottlerin induces Autophagy in Cancer Stem Cells through the formation of autophagosomes as measured by Electron Microscopy and GFP-LC3 puncta formation. The Molecular Docking analysis showed direct interaction between Rottlerin and Protein kinase-C delta, Beclin-1, and Autophagy related proteins. The biochemical analysis of Cancer Stem Cells treated with Rottlerin showed increase in Autophagy induction through the activation of the kinase-AMP. In addition, Rottlerin treatment also induced apoptosis through the suppression of phosphorylated Akt and mTOR, upregulation of phosphorylated kinase-AMP, downregulation of Bcl-2, Bcl-XL, XIAP, and cIAP-1. These results provide a detailed understanding of the mechanism of action of Rottlerin, as a novel Autophagic inducer by targeting multiple sites, which leads to the apoptosis in Cancer Stem Cells. In conclusion, Autophagy modulation which leads to the apoptosis in Cancer Stem Cells can be used as a potential therapeutic option for cancer.
Image guided focused and unfocused ultrasound (US) has been used as a noninvasive technique to enhance delivery of drugs or genes while inducing only minor and transient morphological changes within the treated region. However, the cellular and molecular biological effects of non-thermal focused US (FUS) beyond the structural changes that result in vascular leakage have received limited attention. The mechanotransductive effects induced by pulsed FUS results rapid molecular and cellular changes within tissues providing an opportunity to utilize this approach for novel cellular therapies. In this presentation, I will present how the mechanical effects of pFUS alters tissue microenvironments and can enhance homing permeability and retention (EHPR) of stem cells in targeted tissues. I will present the temporal proteomic changes in muscle, kidney and brain following pFUS exposures and how the alterations in cytokines, chemokines and trophic factors can be modulated by treatment with anti-inflammatory agents and calcium channel blockers will be presented. Examples of how pFUS exposure can be used to precondition tissues to enhance mesenchymal stromal cell tropism along with cell potency by increasing production IL10 and VEGF from infused resulting in improvement in clinical outcomes in disease models and how this approach came potentially be used in regenerative medicine.
Dr. Joseph A. Frank earned his medical degree graduated Stony Brook University and is board certified in Internal Medicine and Medical Oncology. He is a tenured senior investigator in the Clinical Center and Chief of the Frank Laboratory in the Radiology and Imaging Sciences Department, Clinical Center and adjunct senior investigator in the National Institutes of Biomedical Imaging and Bioengineering. He received an undergraduate and Masters degree in Chemistry and his advisor from 1973-1978 was Dr. Paul Lauterbur, the 2003 Nobel Laureate for Physiology and Medicine. HIs lab exploring the effects of ultrasound on the molecular changes in tissue microenvironment to enhance homing permeability and retention of stem cells to targeted tissue as part of a cell therapy strategy for regenerative medicine. Dr. Frank has published over 320 publications and 20 book chapters. Dr. Frank is a Fellow of the International Society of Magnetic Resonance in Medicine and a Fellow of the American College of Physicians.
Cell-based therapy to treat Type I Diabetes Mellitus has been studied and several methods are practically introduced to clinics, and transplantation of healthy allogeneic beta-cells has played reliable results, while consistency of maintaining blood-glucose level, escaping immunological problems, and oncogenesis are generally concerned topics after delivering therapeutic cells into patients. It has been recognized that applying autologous cells are ideal to avoid immunologically oriented problems. Viable multupotent mesenchymal cells are proven to be differentiated toward beta-cells releasing insulin molecules if appropriate niche was provided, while it requires delayed period to reveal biological functions until the delivered cells are properly adapted to the new niche. To reduce the manifesting time, transfecting preproinsulin gene into mesenchymal cell has been studied, but possibility of oncogenesis after transplantation is an unsolved intrinsic problem by using growth factors which also propel differentiation of the mutated cells. To resolve this problem, preparation of mesenchymal cells to release insulin in a culture media by providing controlled niche without using growth factors, and compared them with preproinsulin gene transfected cells in vitro and in vivo.
Hwal (Matthew) SUHhas completed his DDS and MSD from Yonsei University in Seoul, Korea, PhD from Osaka University in Japan. He is a professor of Yonsei University College of Medicine majoring Tissue Regenerative Medicine, and chair of WG on Cell and Stem Cell Engineering of International Federation of Medical and Biological Engineering affiliated to UN and WHO.
Regenerative Medicine offers the promise of an unlimited amount of tissue and organ repair and replacement. Great progress has been made in preclinical studies and many applications are now in the clinical stage. Regenerative Medicine is beginning to explore the potential effects of efficacy in different patient populations. The risk urinary incontinence in women is age and obesity related, and is a chronic disease influenced by the sex hormone milieu. It is well known that aging and diabetes reduce the ability of tissue to regenerate.It also stands to reason that these changes may also influence the efficacy of regenerative medicine approaches to urinary incontinence. In fact, this may explain, in part, why cell therapies for urinary incontinence are so successful in preclinical studies (which historically use younger health animals with acute UI). In contrast, the results of clinical studies in older women with varying body weights, sex hormone status and chronicity of disease. This presentation will first review select studies identifying the effects of age, gender and hormone status on the ability of cells to stimulate regeneration of tissues. The majority of this presentation will introduce a female nonhuman primate (NHP) model of induce intrinsic urinary sphincter deficiency (ISD) and then present results of several studies describing the effects of skeletal muscle precursor cell (skMPC) treatment in acute vs. chronic fibrotic ISD; older and younger NHPs and in NHPs with stress-induced dysmenorrhea. The presentation will close with the results of recent studies identifying the use of chemokines on sphincter regeneration in this animal model.
Dr. Williams is a DVM with over 35 years’ experience performing translational research using different animal models of human disease. He has published over 120 full length manuscripts and 20 chapters and reviews. His focus is on women’s health and recently on regenerative medicine approaches to restoration of the urinary sphincter for women with urinary incontinence. This presentation is a review of determinates of cell therapy efficacy on urinary incontinence
Increase in life expectancy in the developed world often comes with a great cost of diseases and organ failure during later years in life, reducing the quality of life of the elderly. Regenerative medicine and tissue engineering aim at repairing and/or replacing human tissues and organs in order to restore normal functions. Liver disease is a significant contributor to impaired quality of life, and possibly death, Liver transplantation is presently the best therapy able to extend survival for end-stage liver disease; however, it is severely limited by the availability of donor organs. We established a novel approach for whole organ engineering using decellularization of animal and human organs to create organ-specific extracellular matrix (ECM) scaffolds, subsequently recellularized with human liver stem cells (hLSCs). The engineered livers performed many synthetic and metabolic functions and were successfully transplanted in rats. To advance this technology to clinical translation, we have initiated a 3 pronged approach: 1) Determining conditions for optimal liver tissue reorganization inside the liver ECM scaffolds; 2) Identifying conditions to differentiate the human liver stem cells into hepatocytic and biliary lineages; and 3) Scaling up the decellularization/recellularization technology to livers with clinically appropriate size. These results demonstrate efficient generation of bioengineered human livers that recapitulates stepwise development of hepatocyte and bile duct formation. The bioengineered livers demonstrated self-organization of human liver tissue inside the liver ECM scaffolds. The use of porcine livers as scaffold donors represents a feasible approach for bioengineering livers for clinical use.
Dr. Soker received his Ph.D. from the Technion-Israel Institute for Technology and was postdoctoral trainee and an Assistant Professor at the Harvard Medical School. Hethen moved to the Wake Forest School of Medicine to build the Wake Forest Institute for Regenerative Medicine and he is currently a tenured Professor of Regenerative Medicine, Biomedical Engineering, Cancer Biology and Surgical Sciences. Dr. Soker’s research focuses on identification of new sources of cells and scaffolds for tissue engineering, tissue neovascularization, and real-time imaging. Among his contributions are the integration of molecular and cellular biology principles in regenerative medicine applications.
Human adipose stem cells (hASCs) have been usually cultivated in fetal bovine serum (FBS)-based medium. Recently, clinical use of hASCs urges us to switch FBS to human serum (HS)for regulatory purpose. However, it is not fully understood how HS affects the characteristicsand activity of hASCs. This study investigated the functional comparability between HS- andFBS-based culture medium in terms of characteristics, proliferation and differentiation ofhASCs. hASCs were isolated from the abdominal or gluteal tissues (SA-1, 55; SG-1, 53)from surgical operations at Inha University Hospital. Then, hASCs were cultured either in acommercial growth medium supplemented with 10% FBS and 5ng/ml bFGF or in α-MEMsupplemented with HS. hASCs were expanded until 9 passages, during which the doublingtime (DT) of cells were calculated to assess their proliferation ability. hASCs were alsoexamined for the expression of MSCs markers of CD105, CD90 and CD73 by FACS, selfrenewalby CFU-F assay, and multi-differentiation potential to adipogenic and osteogeniclineages. In the results, hASCs cultured in HS-based medium showed similar levels of CFU-Fand multi-differentiation potential to those cultured in FBS-based medium. In contrast, theaverage DT of hASCs was shorter in the HS-based medium than in the FBS-based medium.Therefore, the HS-based medium showed better performance than the FBS-based medium inthe hASCs cultivation in vitro without compromising their stem cell properties.