Clinical Applications & Clinical Translation of Tissue Engineering Agenda

Coffee Break, Networking, Exhibit and Poster Viewing

Using Microfluidics to Grow Perfusable Vascular Networks
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

For years, one of the major hurdles in the creation of engineered tissues was the unmet need for a microvascular network.  Recently, several groups have reported the development of microfluidic systems incorporating 3D co-culture of endothelial cells and fibroblasts to produce perfusable networks of microvessels, paving the way for more complex systems with other cell types for specific organ or tissue functions.  These in vitro systems can be maintained long-term, raising the prospect of generating complete tissues in vitro for various purposes including organs for implantation or non-medical applications.  Several challenges yet need to be addressed, including the control of network morphology and stabilization of the networks once established. Both the current state-of-the-art and the directions of future research will be addressed.

Microfluidic Microvasculature for Tissue Engineering
Rong Fan, Harold Hodgkinson Professor of Biomedical Engineering, Yale University, United States of America

A major challenge in tissue engineered organ transplantation is revascularization. How to fabricate a perfusable microvascular network in neotissue to support the tissue growth in vivo is crucial. We are working to address this problem by developing a two-step approach for synthesizing neotissues with perfusable microvasculature. First we use a microfluidic system to create a large-scale endothelialized microvessels that can be retrieved to form a free-standing microvascular network. Second, this microvascular network is used as a template to seed perivascular and tissue specific cells to grow neotissues. This modular approach is generic and versatile for the potential application to a range of functional tissues including liver, bone, and pancreatic tissues.

Bottom-up Engineering of Bio-artificial 3D-Tissues on Microfluidic Chip for Organ Regeneration
Sang Hoon Lee, Professor, Korea University, Korea South

In this presentation, we present bottom-up assembly of 3D micro tissues and their application to liver, pancreas, and brain: 1) we have fabricated rat hepatocyte spheroid and hetero-spheroid including hepatocyte and hepatic stellate cell, even with vascular structure, and proved its application of ready-to-use xenogenic bioartificial liver by encapsulating with hydrogel. Human hepatocyte spheroid co-cultured with human adipose stem cells were engineered to enhance the spheroid aggregation and hepatocyte function, 2) we have engineered islet spheroid and performed in situ encapsulation for glucose control of mouse, and 3) we have also created neuronal spheroid networked each other for brain study including amyloid-beta effect on 3D neurons. We expect that these well-defined 3D tissues will be used as in vivo mimicking drug screening and disease model. If the proposed technology is combined to the 3D assembling technology such as bioprinting, more functionalized tissues could be constructed and, we expect that they could be used broadly for the regeneration of damaged organ.

Applications Development with 3D Human Tissues created via Additive Manufacturing Approaches
Sharon Presnell, Executive Vice President, R&D , Organovo, Inc., United States of America

Additive manufacturing is emerging as a compelling means to generate three-dimensional structures comprising living cells for use in in vitro and in vivo applications, with an exceptional degree of architectural control. The value of tissues produced using these methodologies will be determined, ultimately, by their functional performance in in vitro and in vivo applications. Phenotypic and functional attributes of 3D-bioprinted human tissues, such as liver, will be discussed.

Networking Reception: Enjoy Premium Beers, California Wines, and Appetizers with Your Colleagues with a Beautiful View of Boston and The Charles River

Close of Day 1 of the Conference

Morning Coffee and Breakfast Pastries

Novel, Cellular Biomarkers Indicating Tissue-specific, Regenerative Potential
Eric Darling, Associate Professor of Medical Science, Engineering, and Orthopaedics, Brown University, United States of America

Mesenchymal stem/stromal cells (MSCs) have garnered intense interest for their application in tissue engineering and regenerative medicine therapies. Unfortunately, the heterogeneity inherent in these cell populations complicates their use. Traditional, surface marker-based approaches have had limited success purifying autologous MSCs at sufficient cell yields such that ex vivo expansion is not required. Recently, our group has shown that both single-cell mechanical properties and live-cell gene expression signals can be used to predict the differentiation potential of MSCs. These approaches target all cells in stem/stromal populations that are capable of producing lineage-specific metabolites, encompassing a broader swathe of cell types and differentiation states than traditional techniques. In mechanical property-based experiments, we have shown that less compliant MSCs are more likely to deposit large amounts of calcified matrix compared to more compliant MSCs following osteogenic induction. Conversely, more compliant MSCs showed a propensity to produce large amounts of intracellular lipids following adipogenic induction. In gene expression-based experiments, we have shown that MSCs can be sorted using a fluorescent marker that binds to early osteogenic mRNA molecules, resulting in cell populations that deposited larger amounts of calcified matrix deposition over unsorted controls. Cell yields were also significantly higher than standard, cell enrichment approaches. While osteogenesis has been the primary target of investigation, continuing work is applying these techniques to other cell types and tissues.

The Use Of PRP and Stem Cell injections in an Office Setting
Joseph Purita, Medical Director of Stem Cell Centers of America, Institute Of Regenerative and Molecular Orthopedics, United States of America

This presentation concerns PRP and Stem Cell (both bone marrow and adipose) injections for musculoskeletal conditions in an office setting.  Indications are given as to which type of cell and technique to use to accomplish repair.  Stem cells, both bone marrow derived (BMAC) and adipose, are used for the more difficult problems..  PRP injections are utilized for the less severe tendon problems.  Discussed are the indications of when to use Stem Cells verses PRP and when to use both.  The newest concepts in stem cell science are presented. These concepts include the clinical use of MUSE cells, exosomes, and Blastomere like stem cells.  Basic science of both PRP and stem cells are discussed.  This presentation defines what constitutes an effective PRP preparation.  Myths concerning stem cells are dispelled.  One myth is that mesenchymal stem cells are the most important stem cell.  This was the initial interpretation of Dr.  Arnold Caplan the father of mesenchymal stem cell science.  Dr. Caplan now feels that MSCs have an immunomodulation capacity which may have a more profound and immediate effect on joint chemistry and biology.  We learn that the hematopoietic stem cells are the drivers of tissue regeneration.  Also discussed are adjuncts used which enhance the results. Therapies include supplements, LED therapy, laser, electrical stimulation, and cytokine therapy.  The scientific rationale is presented for each of these entities as to how they have a direct on stem cells.

Sports Medicine and Stem Cells: A Clinical Transformation
Dennis Lox, Physician, Florida Spine and Sports Medicine Center, United States of America

Athletic endeavor has always intertwined with pursuing optimal physical performance. This, coupled with the inherent risk of traumatic injury has placed sports medicine at the forefront of progressive treatment. The emergence of Regenerative Medicine has led to the clinical translation of sports medicine related problems. The use of Platelet Rich Plasma (PRP) and Stem Therapy are cornerstones of this model. The scientific literature will be explored to provide a foundation for the pathophysiology of injury and trauma as it relates to sports medicine, and the regulation of catabolic responses through cellular signaling and cytokines. The rationale for the use of Stem Cell Therapy and PRP in sports medicine is presented. Various clinical cases are presented to illustrate the utilization of stem cell therapy and PRP as a therapeutic strategy to assist athletes in their return to sport. Select situations in which standard medical treatment is a surgical intervention, may be unsuitable for return to sport. A Regenerative Medicine treatment model incorporating Stem Cell Therapy, may provide suitable alternative strategies that facilitate healing and repair, without precluding return to sport. In the sports medicine world success is measured by return to sport. The clinical translation of Stem Cell Therapy into sports medicine, may foster a transformation of treatment strategy.

Coffee Break, Networking, Exhibit and Poster Viewing

Human Microphysiological Systems of Blood Vessels and Skeletal Muscle for Drug Toxicity
George Truskey, R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, Duke University, United States of America

Skeletal muscle is important for drug and toxicity testing given the relative size of the muscle mass and cardiac output that passes through muscle beds, the key role of muscle in energy substrate metabolism and diabetes, its role in mediating the severity of peripheral arterial disease and heart failure, and the need for therapies for muscle diseases such as muscular dystrophy and sarcopenia. To develop a system for functional and drug testing under physiological conditions, we developed three-dimensional skeletal muscle cultures and tissue engineered blood vessels (TEBV) with a functional endothelial layer. TEBVs are of arteriolar dimensions (inner diameters between 400 µm and 800 µm) and vasoconstriction induced by 1 µM phenylephrine was stable over 5 weeks of culture. TEBVs relaxed in the presence of acetylcholine only when endothelial cells were present, consistent with their role in vascular function. The TEBV exhibited responses to inflammatory stimuli suggesting injury and repair.  Human engineered muscle bundles exhibited contraction after electrical stimulation and tetanus at high frequency of stimulation. HuMB routinely achieve twitch and tetanic contractile forces > 0.5 mN and1 mN, respectively and exhibit typical Frank-Starling like twitch force-length relationship and passive tension-length relationship.  Both TEBV and HuMB exhibited responses to Drugs similar to those observed in vivo. Supported by UH2/UH3TR000505 and the NIH Common Fund for the Microphysiological Systems Initiative.

Networking Lunch, Visit the Exhibitors and Poster Viewing

Why Manufacturing Matters: How Today’s Cell Therapy BioProcess Innovations are Laying the Foundation for a Sustainable Tissue Engineering Revolution
Jon Rowley, Chief Executive And Technology Officer, Rooster Bio Inc, United States of America

Technology is rapidly moving toward the integration of biologics into products like cell therapies, engineered tissues, bio-robotics, implantable devices, 3D printing, food, clothing, and even toys.  This coming decade will see the incorporation of living cells into all these platforms and others not yet imagined. To expedite this biologics revolution, inventors, developers and suppliers will require a limitless, standardized, low-cost supply of living cells – and today’s cell therapy bio-manufacturing innovations are laying the groundwork to make this a reality.

Bioengineering Strategies for Improved Clinical Impact of Cell-based Therapies
Oren Levy, Instructor of Medicine, Harvard Medical School/Brigham and Women’s Hospital, United States of America

A key focus of bioengineering research is to develop effective stem cell therapies to treat a wide range of diseases. This talk will focus on bioengineering strategies to enhance control over cell fate following transplantation. Specifically, approaches to control cell targeting to sites of disease to maximize therapeutic impact and new perspectives in the area of cell therapy will be discussed.

Round-Table Breakout Discussions

Close of Day 2 of the Conference