Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC

Kenichi Tamama,Alan Wells,Haruhisa Kawasaki

doi:10.1155/2010/795385

Abstract

Adult bone marrow multipotential stromal cells (MSCs) hold great promise in regenerative medicine and tissue engineering. However, due to their low numbers upon harvesting, MSCs need to be expanded in vitro without biasing future differentiation for optimal utility. In this concept paper, we focus on the potential use of epidermal growth factor (EGF), prototypal growth factor for enhancing the harvesting and/or differentiation of MSCs. Soluble EGF was shown to augment MSC proliferation while preserving early progenitors within MSC population, and thus did not induce differentiation. However, tethered form of EGF was shown to promote osteogenic differentiation. Soluble EGF was also shown to increase paracrine secretions including VEGF and HGF from MSC. Thus, soluble EGF can be used not only to expand MSC in vitro, but also to enhance paracrine secretion through drug-releasing MSC-encapsulated scaffolds in vivo. Tethered EGF can also be utilized to direct MSC towards osteogenic lineage both in vitro and in vivo.

Highlights

Adult bone marrow multipotential stromal cells (MSCs) hold great promise in regenerative medicine and tissue engineering
We focus on the potential use of epidermal growth factor (EGF), prototypal growth factor for enhancing the harvesting and/or differentiation of MSCs
Adult bone marrow multipotential stromal cells / mesenchymal stem cells (MSCs) are multipotent cells with strong paracrine activities of various growth factors [1,2,3,4,5,6,7]. These cells were originally isolated as colony forming adherent fibroblast-like cells or colony forming unit fibroblastic cells (CFU-Fs) from bone marrow suspension [8], but it was subsequently realized that these cells carry multipotency capable of differentiating into multiple cell lineages including osteoblasts, chondrocytes, adipocytes, smooth muscle cells, skeletal and cardiac myocytes, endothelial cells, and neurons [3,4,5,6, 9, 10]

Summary

EGF to Enhance Self-Renewal and Expansion of MSCs In Vitro

Our data show that EGF alone does not induce differentiation in the absence of chemical or other cues, and does not alter human MSC differentiation processes into osteogenic, adipogenic, and chondrogenic lineages by chemical cues in vitro [3] This discrepant finding might be attributable to a different intracellular signaling, as PI3Kprotein kinase B/akt pathway is activated in the downstream of EGFR/ErbB-1 in our report [3], whereas this pathway is not activated in their report [46]. Tethered EGF blocks EGFR/ErbB1 endocytic internalization and enhances osteogenic differentiation through providing sustained activation of downstream signaling through EGFR/ErbB1, whereas 80 pM of soluble EGF interferes with osteogenic differentiation through inducing receptor internalization and subsequent degradation [47], in agreement with Krampera’s data [45]. Soluble EGF can still be used to expand MSCs in vitro without inducing differentiation or sacrificing differentiation potentials

EGF Treatment to Enhance Therapeutic Potentials of MSC

Findings

Epilogue