Biophysical Regulation of Stem Cell Differentiation
- PDF / 217,846 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 99 Downloads / 251 Views
SKELETAL BIOLOGY (DB BURR, SECTION EDITOR)
Biophysical Regulation of Stem Cell Differentiation Peter M. Govey & Alayna E. Loiselle & Henry J. Donahue
Published online: 27 March 2013 # Springer Science+Business Media New York 2013
Abstract Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells—the most broadly studied source of osteoblastic progenitors—undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loadinginduced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche. Keywords Stem cell . Differentiation . Osteogenesis . Biophysical . Signaling . Mechanical loading . Fluid flow . Osteocyte . Strain . Shear stress . Topography . Allograft . Cell fate . Progenitor . Connexin 43 . Cx43 . Hemichannel . Gap junction . Hydrostatic . Intramedullary pressure . Scaffold
P. M. Govey : A. E. Loiselle : H. J. Donahue (*) Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, 500 University Drive, MC: H089, Hershey, PA, USA e-mail: [email protected]
Introduction Whether through day-to-day exercise or more artificiallyinduced means, modest magnitudes of whole-bone mechanical loading correlate with higher bone density and greater fracture resistance. Herein, we review recent advances in our understanding of this biophysical “black box” between bone’s macro-scale mechanical milieu and induced changes in gene expression leading to stem cell differentiation and increased net bone formation. Continued advances building on this knowledge will exploit these biophysical control systems to stimulate osteogenic capacity of stem cells for therapeutic benefit. A spectrum of pathologies results when the multi-cellular remodeling process is out of balance. Excessive net resorption leads to osteopenia and osteoporosis, and hormonal actions remove calcium from this mineral reservoir. On the other hand, insufficient remodeling and micro-crack accumulation manifest as stress fractures or failed bone grafts. Stem cells from aged bone decline in osteogenic differentiation capacity due to a dysfunction in the mechanisms of biophysically-induced adaptation to loading [1, 2]. Understanding biophysical regulation of stem
Data Loading...
