[SUSPICIOUS MESSAGE] [GRG] mechanically functional human cartilage grown – Columbia Engineering

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Large, stratified, and mechanically functional human cartilage
grown in vitro by mesenchymal condensation

Sarindr Bhumiratanaa,
Ryan E. Etona,
Sevan R. Oungoulianb,
Leo Q. Wanc,
Gerard A. Ateshianb, and
Gordana Vunjak-Novakovica,1

Significance

The ability to regenerate functional cartilage from adult human
mesenchymal stem cells would have tremendous clinical impact.
Despite significant efforts, mechanically functional human
cartilage has not been grown in vitro. We report engineering of
functional human cartilage from mesenchymal stem cells, by
mimicking the physiologic developmental process of mesenchymal cell
condensation. Condensed mesenchymal bodies were induced to fuse and
form mechanically functional cartilaginous tissue interfacing with
bone, without using a scaffolding material. We demonstrate that
this simple “biomimetic” approach can be used to generate
centimeter-sized, anatomically shaped pieces of human cartilage
with physiologic stratification and mechanical properties.
Functional human cartilage grown from a patient’s own cells using
this method could greatly accelerate the development of new
therapeutic modalities for cartilage repair.

Abstract

The efforts to grow mechanically functional cartilage from human
mesenchymal stem cells have not been successful. We report that
clinically sized pieces of human cartilage with physiologic
stratification and biomechanics can be grown in vitro by
recapitulating some aspects of the developmental process of
mesenchymal condensation. By exposure to transforming growth factor-
β, mesenchymal stem cells were induced to condense into cellular
bodies, undergo chondrogenic differentiation, and form
cartilagenous tissue, in a process designed to mimic mesenchymal
condensation leading into chondrogenesis. We discovered that the
condensed mesenchymal cell bodies (CMBs) formed in vitro set an
outer boundary after 5 d of culture, as indicated by the expression
of mesenchymal condensation genes and deposition of tenascin.
Before setting of boundaries, the CMBs could be fused into
homogenous cellular aggregates giving rise to well-differentiated
and mechanically functional cartilage. We used the mesenchymal
condensation and fusion of CMBs to grow centimeter-sized,
anatomically shaped pieces of human articular cartilage over 5 wk
of culture. For the first time to our knowledge biomechanical
properties of cartilage derived from human mesenchymal cells were
comparable to native cartilage, with the Young’s modulus of >800
kPa and equilibrium friction coeffcient of <0.3. We also
demonstrate that CMBs have capability to form mechanically strong
cartilage–cartilage interface in an in vitro cartilage defect
model. The CMBs, which acted as “lego-like” blocks of neocartilage,
were capable of assembling into human cartilage with physiologic-
like structure and mechanical properties.

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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