[GRG] Expansion of Human Stem and Progenitor Cells w/o genetic modification

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105525

Expansion of Human and Murine Hematopoietic Stem and Progenitor
Cells Ex Vivo without Genetic Modification Using MYC and Bcl-2
Fusion Proteins
Gregory A. Bird,

Avital Polsky,

Patricia Estes,
Teri Hanlon,

Haley Hamilton, John J. Morton,
Jonathan Gutman,
Antonio Jimeno,
Brian C. Turner equal contributor,
Yosef Refaeli equal contributor mail

Published: August 29, 2014
•DOI: 10.1371/journal.pone.0105525

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Abstract

The long-term repopulating hematopoietic stem cell (HSC) population
can self-renew in vivo, support hematopoiesis for the lifetime of
the individual, and is of critical importance in the context of
bone marrow stem cell transplantation. The mechanisms that regulate
the expansion of HSCs in vivo and in vitro remain unclear to date.
Since the current set of surface markers only allow for the
identification of a population of cells that is highly enriched for
HSC activity, we will refer to the population of cells we expand as
Hematopoietic Stem and Progenitor cells (HSPCs). We describe here a
novel approach to expand a cytokine-dependent Hematopoietic Stem
and Progenitor Cell (HSPC) population ex vivo by culturing primary
adult human or murine HSPCs with fusion proteins including the
protein transduction domain of the HIV-1 transactivation protein
(Tat) and either MYC or Bcl-2. HSPCs obtained from either mouse
bone marrow, human cord blood, human G-CSF mobilized peripheral
blood, or human bone marrow were expanded an average of 87 fold,
16.6 fold, 13.6 fold, or 10 fold, respectively. The expanded cell
populations were able to give rise to different types of colonies
in methylcellulose assays in vitro, as well as mature hematopoietic
populations in vivo upon transplantation into irradiated mice.
Importantly, for both the human and murine case, the ex vivo
expanded cells also gave rise to a self-renewing cell population in
vivo, following initial transplantation, that was able to support
hematopoiesis upon serial transplantation. Our results show that a
self-renewing cell population, capable of reconstituting the
hematopoietic compartment, expanded ex vivo in the presence of Tat-
MYC and Tat-Bcl-2 suggesting that this may be an attractive
approach to expand human HSPCs ex vivo for clinical use.

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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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