Mesenchymal stromal cells: misconceptions and evolving concepts

Abstract

Nearly half a century has passed since the publication of the first articles describing plastic-adherent cells from bone marrow, referred to initially as colony-forming unit fibroblasts, then marrow stromal cells, mesenchymal stem cells and most recently multipotent mesenchymal stromal cells (MSCs). As expected, our understanding of the nature and biologic functions of MSCs has undergone major paradigm shifts over this time. Despite significant advances made in deciphering their complex biology and therapeutic potential in both experimental animal models and human clinical trials, numerous misconceptions regarding the nature and function of MSCs have persisted in the field. Continued propagation of these misconceptions in some cases may significantly impede the advancement of MSC-based therapies in clinical medicine. We have identified six prevalent misconceptions about MSCs that we believe affect the field, and we attempt to rectify them based on current available data.

Introduction

Over the past several decades, concepts regarding the nature and function of mesenchymal stromal cells (MSCs) have undergone numerous major paradigm shifts. Pioneering studies by Friedenstein and colleagues first revealed that MSCs were capable of sustaining hematopoiesis and functioned as progenitors of adipogenic, chondrogenic and osteogenic lineages, properties exploited in early clinical trials 1, 2, 3. As interest in MSCs expanded, studies conducted in experimental animal models revealed the cells also possessed potent tissue reparative properties. Initial studies attributed this activity to direct cell replacement via the transdifferentiation of transplanted MSCs. However, subsequent work by many laboratories revealed that MSCs promote tissue repair via paracrine action. In recent years, the therapeutic potency of MSCs has been attributed to the secretion by cells of a large number of factors that possess angiogenic, trophic, neuro-regulatory, immunomodulatory, and anti-inflammatory activity. However, as concepts became outmoded and replaced with new paradigms, many misconceptions related to the nature and biology of MSCs arose. In this article, we identify at least six misconceptions (Figure 1) that have persisted over the years and serve as potential impediments to the successful therapeutic application of MSCs. Where possible, we attempt to clarify these misconceptions based on available published literature.