Effects of TGF-β and b-FGF on the Potential of Peripheral Blood-Borne Stem Cells and Bone Marrow-Derived Stem Cells in Wound Healing in a Murine Model

Abstract

Peripheral blood fibrocytes make up a newly identified leukocyte subpopulation that displays fibroblast-like properties. These blood-borne cells can rapidly enter the site of injury at the same time as circulating inflammatory cells. Marrow stroma includes a subpopulation of undifferentiated cells that are capable of becoming one of a number of phenotypes, including chondrocytes, osteoblasts, adipocytes, and fibroblasts. Adult human bone marrow contains a minority population of bone marrow mesenchymal stem cells (BMSCs) that contribute to the regeneration of tissues such as bone, cartilage, muscle, ligaments, tendons, fat, and stroma. Evidence that these BMSCs are pluripotent, rather than being a mixture of committed progenitor cells each with a restricted potential, includes their rapid proliferation in culture. We hypothesized that peripheral blood mesenchymal stem cells (PBMSCs) and BMSCs have an effective role in wound healing. In this study, we identified and quantified the marrow stem cells (MSCs) derived from blood and bone marrow recruited and migrated to the wound site. Our results show that the synergistic effects of transforming growth factor-beta (TGF-β) and basic fibroblast growth factor (b-FGF) lead to a significant increase in migration and recruitment of both PBMSCs and BMSCs to the wound site, with more potent effects on PBMSCs as compared with BMSCs. Reverse transcription polymerase chain reaction of collagen type I (COL1A1) transcripts (348 bp) confirmed that TGF-β and b-FGF activate collagen I (production in marrow stem cells at higher transcription levels), with more vigorous effects of TGF-β on PBMSCs as compared with the same condition on BMSCs.