Bone Marrow-Derived Mesenchymal Stromal Cells: A Novel Target to Optimize Hematopoietic Stem Cell Transplantation Protocols in Hematological Malignancies and Rare Genetic Disorders.

Stefania Crippa,Maria Ester Bernardo,Giulia Porro,Roberto Bosotti,Ludovica Santi

doi:10.3390/jcm9010002

Stefania Crippa, Maria Ester Bernardo + Show 3 more

Open Access

https://doi.org/10.3390/jcm9010002

Copy DOI

Abstract

Mesenchymal stromal cells (MSCs) are crucial elements in the bone marrow (BM) niche where they provide physical support and secrete soluble factors to control and maintain hematopoietic stem progenitor cells (HSPCs). Given their role in the BM niche and HSPC support, MSCs have been employed in the clinical setting to expand ex-vivo HSPCs, as well as to facilitate HSPC engraftment in vivo. Specific alterations in the mesenchymal compartment have been described in hematological malignancies, as well as in rare genetic disorders, diseases that are amenable to allogeneic hematopoietic stem cell transplantation (HSCT), and ex-vivo HSPC-gene therapy (HSC-GT). Dissecting the in vivo function of human MSCs and studying their biological and functional properties in these diseases is a critical requirement to optimize transplantation outcomes. In this review, the role of MSCs in the orchestration of the BM niche will be revised, and alterations in the mesenchymal compartment in specific disorders will be discussed, focusing on the need to correct and restore a proper microenvironment to ameliorate transplantation procedures, and more in general disease outcomes.

Highlights

Mesenchymal stromal cells (MSCs) are a rare population of non-hematopoietic multipotent cells resident in the bone marrow (BM), which offer physical support and regulate hematopoietic stem/progenitor cell (HSPC) homeostasis
In the field of hematopoietic stem cell transplantation (HSCT), MSCs have been extensively studied for their capacity to sustain HSPC and facilitate their engraftment
HSCT is an available curative option for several hematological malignant and nonmalignant compartment may be evaluated in some pathologies

Summary

Introduction

Mesenchymal stromal cells (MSCs) are a rare population of non-hematopoietic multipotent cells resident in the bone marrow (BM), which offer physical support and regulate hematopoietic stem/progenitor cell (HSPC) homeostasis. MSCs can be expanded for several passages as fibroblast-like cells In vitro, they are positive for the expression of specific surface markers, classification determinant (CD)105, CD90, and CD73, whereas they do not express hematopoietic (CD34, CD45) and endothelial markers (CD31). Genome-wide analysis has revealed a distinct transcriptional profile of human primary MSCs and corresponding in vitro counterpart, highlighting an enhanced hematopoietic supportive function in primary MSCs [22] For this reason, the manipulation of culture conditions, including cytokines, glucose concentration, oxygen tension, culture as mesenspheres, have been proposed as a strategy to maintain MSC native properties [27,28,29], including their capacity to support HSPCs. More recently, the use of a cocktail of transcription factors has been shown to reprogram murine ex vivo expanded MSCs to a more primitive state [30].

MSCs as Key Elements of the Bone Marrow Niche

MSCs in the Clinical Use

MSCs in Hematological Malignancies

Representative