Abstract
Mesenchymal stem/stromal cells (MSCs) are undergoing intensive translational research for several debilitating conditions, including critical illnesses such as ARDS and sepsis. MSCs exert diverse biologic effects via their interaction with host tissues, via mechanisms that require the MSC to be in close proximity to the area of injury. Fully harnessing the therapeutic potential of advanced medicinal therapeutic products such as MSCs and their successful translation to clinical use requires a detailed understanding of MSC distribution and persistence in the injured tissues.Key aspects include understanding MSC distribution within the body, the response of the host to MSC administration, and the ultimate fate of exogenously administered MSCs within the host. Factors affecting this interaction include the MSC tissue source, the in vitro MSC culture conditions, the route of MSC administration and the specific issues relating to the target disease state, each of which remains to be fully characterised. Understanding these factors may generate strategies to modify MSC distribution and fate that may enhance their therapeutic effect.This review will examine our understanding of the mechanisms of action of MSCs, the early and late phase distribution kinetics of MSCs following in vivo administration, the ultimate fate of MSCs following administration and the potential importance of these MSC properties to their therapeutic effects. We will critique current cellular imaging and tracking methodologies used to track exogenous MSCs and their suitability for use in patients, discuss the insights they provide into the distribution and fate of MSCs after administration, and suggest strategies by which MSC biodistribution and fate may be modulated for therapeutic effect and clinical use.In conclusion, a better understanding of patterns of biodistribution and of the fate of MSCs will add important additional safety data regarding MSCs, address regulatory requirements, and may uncover strategies to increase the distribution and/or persistence of MSC at the sites of injury, potentially increasing their therapeutic potential for multiple disorders.
Highlights
Mesenchymal stem/stromal cells (MSCs) were first described in the 1970s as a clonogenic fibroblast precursor cell population of the bone marrow, referred to at the time as ‘colony forming unit fibroblasts’ [1, 2]
We will critique the cellular imaging and tracking methodologies currently used to track exogenous MSCs, discuss the insights they provide into the distribution and fate of MSCs after administration, and suggest strategies by which MSC biodistribution and fate may be modulated for therapeutic effect
Limitations in our understanding of the biodistribution and fate of therapeutically administered MSCs within the body constitute a significant impediment to successful clinical translation of MSCs
Summary
Mesenchymal stem/stromal cells (MSCs) were first described in the 1970s as a clonogenic fibroblast precursor cell population of the bone marrow, referred to at the time as ‘colony forming unit fibroblasts’ [1, 2]. A better understanding of patterns of biodistribution and of the fate of MSCs will uncover strategies to enhance strategic targeting and/or persistence of MSC at the sites of injury, potentially increasing their therapeutic ability. Nystedt and colleagues have demonstrated a role for cellular interactions mediating MSC retention in the lungs [23] They reported that umbilical cord-derived MSCs. In summary, a better understanding of patterns of biodistribution and of the fate of MSCs will uncover strategies to increase the distribution and/or persistence of MSC at the sites of injury, potentially increasing their therapeutic potential for multiple disorders, including critical illnesses such as ARDS and sepsis. There are several methods of cell labelling, and developments in recent years have allowed higher resolution, more accurate and long-term analyses of their journey in vivo
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