Toward biomimetic materials in bone regeneration: Functional behavior of mesenchymal stem cells on a broad spectrum of extracellular matrix components

Abstract

Bone defect treatments can be augmented by mesenchymal stem cell (MSC) based therapies. MSC interaction with the extracellular matrix (ECM) of the surrounding tissue regulates their functional behavior. Understanding of these specific regulatory mechanisms is essential for the therapeutic stimulation of MSC in vivo. However, these interactions are presently only partially understood. This study examined in parallel, for the first time, the effects on the functional behavior of MSCs of 13 ECM components from bone, cartilage and hematoma compared to a control protein, and hence draws conclusions for rational biomaterial design. ECM components specifically modulated MSC adhesion, migration, proliferation, and osteogenic differentiation, for example, fibronectin facilitated migration, adhesion, and proliferation, but not osteogenic differentiation, whereas fibrinogen enhanced adhesion and proliferation, but not migration. Subsequently, the integrin expression pattern of MSCs was determined and related to the cell behavior on specific ECM components. Finally, on this basis, peptide sequences are reported for the potential stimulation of MSC functions. Based on the results of this study, ECM component coatings could be designed to specifically guide cell functions.

A Nonhuman Primate Model of Lung Regeneration: Detergent-Mediated Decellularization and Initial In Vitro Recellularization with Mesenchymal Stem Cells

“…Ode and colleagues have provided an excellent profile of human MSC integrin expression and a morphological characterization of the functional behavior of MSC on various ECM proteins. 26 A similar integrin expression profile of rhesus MSC as well as integrin inhibition studies may provide clues as to the preferential interactions of MSC with the parenchymal and vascular ECM, which may help tailor tissue-engineering approaches using these cells. 26,38 An important consideration toward the applicability of stem cells in lung regeneration is their ability to differentiate along pulmonary lineages.…”

“…26 A similar integrin expression profile of rhesus MSC as well as integrin inhibition studies may provide clues as to the preferential interactions of MSC with the parenchymal and vascular ECM, which may help tailor tissue-engineering approaches using these cells. 26,38 An important consideration toward the applicability of stem cells in lung regeneration is their ability to differentiate along pulmonary lineages. ESC can differentiate into a multitude of cell lineages, including respiratory epithelium.…”

“…Recent studies have shown that the ECM contributes to the functional behavior of MSC and may be essential in guiding cell fate during tissue-specific differentiation. 26,27 Macchiarini et al have recently achieved clinical success using autologous bone marrow MSC and nasal epithelium for chondrocyte and luminal epithelium regeneration, respectively, to create bioartificial airways from decellularized cadaveric tracheas. [28][29][30][31][32] Although very encouraging, it is not yet known if a similar approach will be successful in regenerating the distal lung, as data regarding the differentiation of adult-derived MSC into the pulmonary lineage, as referenced above, is limited.…”

“…25,41 Although MSC have thus far been limited to in vitro differentiation into bone, adipose, cartilage, and muscle/tendon, 42,43 much work is underway to expand their growth and differentiation capacities. 26,27 Alternatively, MSC may be more useful for providing a stroma and helping remodel the de-cellularized scaffold matrix as a platform for inoculation with other cell types. More investigation is needed to determine the most appropriate use of these cell types for the purposes of pulmonary regeneration.…”

Hypertensive Rat Lungs Retain Hallmarks of Vascular Disease upon Decellularization but Support the Growth of Mesenchymal Stem Cells

“…Recent studies have shown that the ECM contributes to the functional behavior of MSCs and may be essential in guiding cell fate during tissuespecific differentiation. [42][43][44][45][46][47] Our group has recently demonstrated that bone marrow-and adipose-derived MSCs adhere to and proliferate within decellularized lung scaffolds in a rhesus macaque model of lung tissue engineering. 13 Here, the initial interaction of adipose-derived MSCs with decellularized scaffolds generated from MCT-PHT rat lungs is described in an effort to provide the necessary proof-of-principle that bioartificial organs can be derived from diseased sources.…”