In a new studyin Nature Communications, Stephanopoulos and his colleague Ronit Freeman successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways. Credit: Northwestern University
What if one day, we could teach our bodies to self-heal like a lizard's tail, and make severe injury or disease no more threatening than a paper cut?
Or heal tissues by coaxing cells to multiply, repair or replace damaged regions in loved ones whose lives have been ravaged by stroke, Alzheimer's or Parkinson's disease?
Such is the vision, promise and excitement in the burgeoning field of regenerative medicine, now a major ASU initiative to boost 21st-century medical research discoveries.
ASU Biodesign Institute researcher Nick Stephanopoulos is one of several rising stars in regenerative medicine. In 2015, Stephanopoulos, along with Alex Green and Jeremy Mills, were recruited to the Biodesign Institute's Center for Molecular Design and Biomimetics (CMDB), directed by Hao Yan, a world-recognized leader in nanotechnology.
"One of the things that that attracted me most to the ASU and the Biodesign CMDB was Hao's vision to build a group of researchers that use biological molecules and design principles to make new materials that can mimic, and one day surpass, the most complex functions of biology," Stephanopoulos said.
"I have always been fascinated by using biological building blocks like proteins, peptides and DNA to construct self-assembled structures, devices and materials, and the interdisciplinary and highly collaborative team in the CMDB is the ideal place to put this vision into practice."
Yan's research center uses DNA and other basic building blocks to build their nanotechnology structuresonly at a scale 1,000 times smaller than the width of a human hair.
They've already used nanotechnology to build containers to specially deliver drugs to tissues, build robots to navigate a maze or nanowires for electronics.
To build a manufacturing industry at that tiny scale, their bricks and mortar use a colorful assortment of molecular Legos. Just combine the ingredients, and these building blocks can self-assemble in a seemingly infinite number of ways only limited by the laws of chemistry and physicsand the creative imaginations of these budding nano-architects.
Learning from nature
"The goal of the Center for Molecular Design and Biomimetics is to use nature's design rules as an inspiration in advancing biomedical, energy and electronics innovation through self-assembling molecules to create intelligent materials for better component control and for synthesis into higher-order systems," said Yan, who also holds the Milton Glick Chair in Chemistry and Biochemistry.
Prior to joining ASU, Stephanopoulos trained with experts in biological nanomaterials, obtaining his doctorate with the University of California Berkeley's Matthew Francis, and completed postdoctoral studies with Samuel Stupp at Northwestern University. At Northwestern, he was part of a team that developed a new category of quilt-like, self-assembling peptide and peptide-DNA biomaterials for regenerative medicine, with an emphasis in neural tissue engineering.
"We've learned from nature many of the rules behind materials that can self-assemble. Some of the most elegant complex and adaptable examples of self-assembly are found in biological systems," Stephanopoulos said.
Because they are built from the ground-up using molecules found in nature, these materials are also biocompatible and biodegradable, opening up brand-new vistas for regenerative medicine.
Stephanopoulos' tool kit includes using proteins, peptides, lipids and nucleic acids like DNA that have a rich biological lexicon of self-assembly.
"DNA possesses great potential for the construction of self-assembled biomaterials due to its highly programmable nature; any two strands of DNA can be coaxed to assemble to make nanoscale constructs and devices with exquisite precision and complexity," Stephanopoulos said.
Proof all in the design
During his time at Northwestern, Stephanopoulos worked on a number of projects and developed proof-of-concept technologies for spinal cord injury, bone regeneration and nanomaterials to guide stem cell differentiation.
Now, more recently, in a new study in Nature Communications, Stephanopoulos and his colleague Ronit Freeman in the Stupp laboratory successfully demonstrated the ability to dynamically control the environment around stem cells, to guide their behavior in new and powerful ways.
In the new technology, materials are first chemically decorated with different strands of DNA, each with a unique code for a different signal to cells.
To activate signals within the cells, soluble molecules containing complementary DNA strands are coupled to short protein fragments, called peptides, and added to the material to create DNA double helices displaying the signal.
By adding a few drops of the DNA-peptide mixture, the material effectively gives a green light to stem cells to reproduce and generate more cells. In order to dynamically tune the signal presentation, the surface is exposed to a soluble single-stranded DNA molecule designed to "grab" the signal-containing strand of the duplex and form a new DNA double helix, displacing the old signal from the surface.
This new duplex can then be washed away, turning the signal "off." To turn the signal back on, all that is needed is to now introduce a new copy of single-stranded DNA bearing a signal that will reattach to the material's surface.
One of the findings of this work is the possibility of using the synthetic material to signal neural stem cells to proliferate, then at a specific time selected by the scientist, trigger their differentiation into neurons for a while, before returning the stem cells to a proliferative state on demand.
One potential use of the new technology to manipulate cells could help cure a patient with neurodegenerative conditions like Parkinson's disease.
The patient's own skin cells could be converted to stem cells using existing techniques. The new technology could help expand the newly converted stem cells back in the laband then direct their growth into specific dopamine-producing neurons before transplantation back to the patient.
"People would love to have cell therapies that utilize stem cells derived from their own bodies to regenerate tissue," Stupp said. "In principle, this will eventually be possible, but one needs procedures that are effective at expanding and differentiating cells in order to do so. Our technology does that."
In the future, it might be possible to perform this process entirely within the body. The stem cells would be implanted in the clinic, encapsulated in the type of material described in the new work, and injected into a particular spot. Then the soluble peptide-DNA molecules would be given to the patient to bind to the material and manipulate the proliferation and differentiation of transplanted cells.
Scaling the barriers
One of the future challenges in this area will be to develop materials that can respond better to external stimuli and reconfigure their physical or chemical properties accordingly.
"Biological systems are complex, and treating injury or disease will in many cases necessitate a material that can mimic the complex spatiotemporal dynamics of the tissues they are used to treat," Stephanopoulos said.
It is likely that hybrid systems that combine multiple chemical elements will be necessary; some components may provide structure, others biological signaling and yet others a switchable element to imbue dynamic ability to the material.
A second challenge, and opportunity, for regenerative medicine lies in creating nanostructures that can organize material across multiple length scales. Biological systems themselves are hierarchically organized: from molecules to cells to tissues, and up to entire organisms.
Consider that for all of us, life starts simple, with just a single cell. By the time we reach adulthood, every adult human body is its own universe of cells, with recent estimates of 37 trillion or so. The human brain alone has 100 billion cells or about the same number of cells as stars in the Milky Way galaxy.
But over the course of a life, or by disease, whole constellations of cells are lost due to the ravages of time or the genetic blueprints going awry.
Collaborative DNA
To overcome these obstacles, much more research funding and recruitment of additional talent to ASU will be needed to build the necessary regenerative medicine workforce.
Last year, Stephanopoulos' research received a boost with funding from the U.S. Air Force's Young Investigator Research Program (YIP).
"The Air Force Office of Scientific Research YIP award will facilitate Nick's research agenda in this direction, and is a significant recognition of his creativity and track record at the early stage of his careers," Yan said.
They'll need this and more to meet the ultimate challenge in the development of self-assembled biomaterials and translation to clinical applications.
Buoyed by the funding, during the next research steps, Stephanopoulos wants to further expand horizons with collaborations from other ASU colleagues to take his research team's efforts one step closer to the clinic.
"ASU and the Biodesign Institute also offer world-class researchers in engineering, physics and biology for collaborations, not to mention close ties with the Mayo Clinic or a number of Phoenix-area institutes so we can translate our materials to medically relevant applications," Stephanopoulos said.
There is growing recognition that regenerative medicine in the Valley could be a win-win for the area, in delivering new cures to patients and building, person by person, a brand-new medicinal manufacturing industry.
Explore further: New technology to manipulate cells could help treat Parkinson's, arthritis, other diseases
More information: Ronit Freeman et al. Instructing cells with programmable peptide DNA hybrids, Nature Communications (2017). DOI: 10.1038/ncomms15982
Original post:
Bio-inspired materials give boost to regenerative medicine - Medical Xpress
- Advances in regenerative medicine-based approaches for skin ... - March 9th, 2025
- Regenerative Medicine: Case Study for Understanding and Anticipating ... - March 9th, 2025
- Top 3 Grants in Regenerative Medicine: February 2025 - RegMedNet - March 9th, 2025
- Editorial: Tissue Engineering and Regenerative Medicine: Advances, Controversies, and Future Directions by Frontiers in Bioengineering and... - March 9th, 2025
- Malaysia To Host 7th World Conference On Exercise And Regenerative Medicine - BERNAMA - March 9th, 2025
- Advancing Regenerative Medicine: A Comprehensive Outlook on the Global Cell Therapy Market - openPR - March 9th, 2025
- Worlds First 3D-Printed Penis Implant Successfully Restores Function in Pigs and Rabbits - The Daily Galaxy --Great Discoveries Channel - March 9th, 2025
- AskBio Receives FDA Regenerative Medicine Advanced Therapy designation for Parkinsons disease investigational gene therapy - Bayer - February 24th, 2025
- What is Regenerative Medicine? | Regenerative Medicine | University of ... - February 24th, 2025
- The quest for a communication device that tells cells to regenerate the body - Big Think - February 24th, 2025
- Transforming the future of regenerative medicine - Reuters - February 24th, 2025
- Breakthrough Alzheimer's Treatment Gets Official WHO Recognition - Major Milestone for Rare Disease Therapy - StockTitan - February 24th, 2025
- Regenerative Medicine Pioneer with 35-Year Track Record Takes Scientific Helm at ZEO ScientifiX - StockTitan - February 24th, 2025
- 101 Guide to Regenerative Medicine Types | Applications, Challenges - February 7th, 2025
- Regenerative Medicine | What is it? | ASCPM - February 7th, 2025
- Regenerative medicine and advanced therapy | NIST - February 7th, 2025
- Therapeutic Reprogramming toward Regenerative Medicine - February 7th, 2025
- Novel living biomaterial aims to advance regenerative medicine - February 7th, 2025
- UC Irvine-led discovery of new skeletal tissue advances regenerative ... - February 7th, 2025
- Top 3 Grants in Regenerative Medicine: January 2025 - RegMedNet - February 7th, 2025
- Advancements in lung regeneration: from bench to bedside - February 7th, 2025
- Entos Pharmaceuticals Awarded $4 Million USD in Funding from the California Institute for Regenerative Medicine (CIRM) for its Congenital Generalized... - February 7th, 2025
- Adia Nutrition Officially Enters $15.1 Billion Global Stem Cell Market with Domestic Treatments by Successful Opening of First Florida Location -... - February 7th, 2025
- Cell therapy weekly: iPSC therapy IND for Phase III trial cleared - RegMedNet - February 7th, 2025
- Creative Medical Technology Holdings Expands Collaboration with Greenstone Biosciences to Accelerate iPSCelz - EIN News - February 7th, 2025
- Placental Stem Cell Therapy Solution Market Size And Booming - openPR - February 7th, 2025
- Stem Cells Applications in Regenerative Medicine and Disease ... - December 6th, 2024
- Ageing of stem cells reduces their capacity to form tumours - Nature.com - December 6th, 2024
- Master of Science in Regenerative Medicine and Entrepreneurships FUSION program information session - The Daily | Case Western Reserve University - December 6th, 2024
- BioRestorative Therapies Announces Notice of Allowance of - GlobeNewswire - December 6th, 2024
- Stem Cell Therapy Strategic Business Report 2024 - - GlobeNewswire - December 6th, 2024
- University of Colorado Anschutz Medical Campus-Led Team Receives Up to $46 Million to Develop Innovative Treatment to Cure Blindness - University of... - December 6th, 2024
- Affimed Announces Acimtamig and AlloNK Combination Granted Regenerative Medicine Advanced Therapy (RMAT) Designation by the U.S. Food and Drug... - December 6th, 2024
- Navigating the hope and hype of regenerative medicine - October 14th, 2024
- Cell and Gene Therapy Investment Ticks Up After Hard Few Years - BioSpace - October 14th, 2024
- Crackdowns on Unproven Stem Cell Therapies Worked Abroad - Medpage Today - October 14th, 2024
- How Regenerative Medicine can help you get out of pain without surgery - WJLA - October 14th, 2024
- Regenity Biosciences Receives 510(k) Clearance for RejuvaKnee, a Groundbreaking Regenerative Meniscus Implant Device to Redefine the Standard of Care... - October 14th, 2024
- Buy, Sell, Hold: Cell and Gene Therapy - BioPharm International - October 14th, 2024
- Mayo Clinic offers unique regenerative medicine procedure for knee and ... - September 13th, 2024
- Regenerative Medicine to the Rescue - Cleveland Clinic - September 13th, 2024
- Regenerative medicine applications: An overview of clinical trials - September 13th, 2024
- The Progression of Regenerative Medicine and its Impact on Therapy ... - September 13th, 2024
- Immune cell injection significantly boosts healing of bone, muscle & skin - September 13th, 2024
- Regenerative Medicine Foundation - September 13th, 2024
- BridgeBio Receives FDAs Regenerative Medicine Advanced Therapy (RMAT ... - September 13th, 2024
- Tissue engineering and regenerative medicine approaches in colorectal ... - September 13th, 2024
- Tubular scaffolds boost stem cell-driven bone regeneration in skull defects - Phys.org - September 13th, 2024
- Finding the right path(way) to reduce fat accumulation in the liver - Medical University of South Carolina - September 13th, 2024
- NAMRU EURAFCENT Signs Agreement with Egypt Center for Research and Regenerative Medicine - DVIDS - September 13th, 2024
- BridgeBio Receives FDAs Regenerative Medicine Advanced Therapy (RMAT) Designation for BBP-812 Canavan Disease Gene Therapy Program - StockTitan - September 13th, 2024
- BioNexus Gene Lab Corp. Signs Strategic Partnership MOU with Shenzhen Rongguang Group to Advance Cancer Screening, Precision Medicine, and... - September 13th, 2024
- Neurona Therapeutics Receives $3.8 Million CIRM Grant for the Development of Next Generation Neural Cell Therapy Candidate - Yahoo Finance - September 13th, 2024
- Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets - Nature.com - September 13th, 2024
- Cellino Awarded $25M in Funding from the Advanced Research Projects Agency for Health (ARPA-H) - Business Wire - September 13th, 2024
- HepaTx Enters Collaboration with Mayo Clinic to Advance Cell Therapy Technology for Liver Disease to Clinical Trials - Longview News-Journal - September 13th, 2024
- Obsidian Therapeutics Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for OBX-115 for the Treatment of Advanced Melanoma -... - September 4th, 2024
- Regenerative Medicine in Orthopedic Surgery: Expanding Our Toolbox - Cureus - September 4th, 2024
- Somite.ai takes pre-seed to $10M as it eyes to become the OpenAI of stem cell biology - CTech - September 4th, 2024
- Longeveron Announces Positive Type C Meeting with U.S. FDA Regarding Pathway to BLA for Lomecel-B in Hypoplastic Left Heart Syndrome (HLHS) - Yahoo... - September 4th, 2024
- Study Explores Potential Of 3D Printed Regenerative Breast Implants - Forbes - September 4th, 2024
- Nikon Announces New Image Analysis Functions to Empower Drug Discovery Research for Cancer, Neurological Disease, and Regenerative Medicine - PR... - September 4th, 2024
- Trinity researcher scores 800,000 to boost regenerative medicine - SiliconRepublic.com - September 4th, 2024
- Seeing the future: Zebrafish regenerates fully functional photoreceptor cells and restores its vision - EurekAlert - September 4th, 2024
- Regenerative Medicine Industry Projected to Surge to USD 73,084.2 Million by 2033, Growing at an 18.5% CAGR - Future Market Insights - September 4th, 2024
- What is regenerative medicine? | Northwell Health - July 2nd, 2024
- Science Saturday: A regenerative reset for aging - July 2nd, 2024
- Science Saturday: A year of new directions and advancements for ... - March 29th, 2024
- Diverse ways regenerative medicine is advancing health care - March 29th, 2024
- Stem cell-based regenerative medicine - PMC - National Center for ... - February 27th, 2024
- Regenerative medicine | NIST - February 10th, 2024
- San Jose blood stem cell donor meets 15-year-old whose life he saved in Los Angeles - The Mercury News - May 17th, 2023
- Regenerative medicine: Current therapies and future directions - April 23rd, 2023
- What Is Regenerative Medicine? | Goals and Applications | ISCRM - April 23rd, 2023
- Important Patient and Consumer Information About Regenerative Medicine ... - April 23rd, 2023
- Regenerative medicine can be a boon for those with Drug-Resistant Tuberculosis - Hindustan Times - April 23rd, 2023
- About Regenerative Medicine - Center for Regenerative ... - Mayo Clinic - April 7th, 2023
- Regenerative Medicine | National Institutes of Health (NIH) - April 7th, 2023
- Porcine Vaccine Market is estimated to be US$ 4.41 billion by 2030 with a CAGR of 7.50%during the forecast - EIN News - April 7th, 2023
- Advancing Safe and Effective Regenerative Medicine Products - March 21st, 2023