[Frontiers in Bioscience S3, 69-81, January 1, 2011]

Adipose tissue as a stem cell source for musculoskeletal regeneration

Jeffrey M. Gimble1, Warren Grayson2, Farshid Guilak3, Mandi J. Lopez4, Gordana Vunjak-Novakovic5

1Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, 2Johns Hopkins University, Baltimore, MD, 3Duke University Medical Center, Durham, NC, 4School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 5Columbia University, New York, NY

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Features of stromal vascular fraction and adipose-derived stem cells
3.1. Isolation of stromal vascular fraction and adipose-derived stem cells: frequency and yield
3.2. Advantages and limitations relative to amnion, bone marrow, and placental derived stem cells
3.3. Chondrogenic potential
3.4. Osteogenic potential
3.5. Skeletal muscle potential
3.6. Immunogenic features - autologous vs allogeneic transplantation
3.7. Tissue engineering by using ASCs, 3D scaffolds and perfusion bioreactors
3.8. Combination with gene transduction vectors
4. Perspective and conclusions
5. Acknowledgements
6. References

1. ABSTRACT

Adipose tissue is an abundant, easily accessible, and reproducible cell source for musculo-skeletal regenerative medicine applications. Initial derivation steps yield a heterogeneous population of cells of stromal vascular fraction (SVF) cells. Subsequent adherent selection of the SVF results in a relatively homogeneous population of adipose-derived stromal/stem cells (ASCs) capable of adipogenic, chondrogenic, myogenic, and osteogenic differentiation in vitro on scaffolds in bioreactors and in vivo in pre-clinical animal models. Unlike hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead release immunosuppressive factors, such as prostaglandin E2. These immunomodulatory features suggest that allogeneic and autologous ASCs will engraft successfully for tissue regeneration purposes. The differentiation and expansion potential of ASCs can be modified by growth factors, bio-inductive scaffolds, and bioreactors providing environmental control and biophysical stimulation. Gene therapy approaches using lentiviral transduction can be used to direct differentiation of ASCs to particular lineages. We discuss the utility of ASCs for musculo-skeletal tissue repair and some of the technologies that can be implemented to unlock the full regenerative potential of these highly valuable cells.