۱- Introduction

۲- Mechanisms regulating MSC differentiation

۳- Pericytes as pre-programmed MSC precursors in vivo

۴- Discussion and future considerations

References

Abstract

The increasing application of approaches that allow tracing of individual cells over time, together with transcriptomic and epigenomic analyses is changing the way resident stromal stem cells (mesenchymal stem cells) are viewed. Rather than being a defined, homogeneous cell population as described following in vitro expansion, in vivo, these cells are highly programmed according to their resident tissue location. This programming is evidenced by different epigenetic landscapes and gene transcription signatures in cells before any in vitro expansion. This has potentially profound implications for the heterotypic use of these cells in therapeutic tissue engineering applications.

Introduction

The prototypical mesenchymal stem cell (MSC), isolated from bone marrow (BM) was described over 3 decades ago by Friedenstein [1]. This characterisation was later expanded to include a cell type, isolated from connective tissue stroma that can exhibit stem cell properties in vitro [2, 3]. These observations led many researchers to identify cells in multiple organs that had a similar immunophenotype and characteristic s in vitro of MSCs in that they could be differentiated to form osteoblast -like, chondrocyte -like, and adipocyte -like cells. Tissues included, connective tissue of teeth [4, 5] , muscle [6], adipose [7], dermis [8], heart and liver [9]. These cell populations expressed a number of the by now established MSC gene markers and all shared some common characteristics including morphology, adherence to tissue culture plastic, and trilineage differentiation [9, 10].