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New Cell-Based Therapy Paradigm: Induction of Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells into Pro-Inflammatory MSC1 and Anti-inflammatory MSC2 Phenotypes

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Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 130)

Abstract

Cell-based therapies (CBTs) are quickly taking hold as a revolutionary new approach to treat many human diseases. Among the cells used in these treatments, multipotent mesenchymal stromal cells, also often and imprecisely termed mesenchymal stem cells (MSC), are widely used because they are considered clinically safe, unique in their immune-modulating capabilities, easily obtained from adult tissues, and quickly expanded as well as stored. However, despite these established advantages, there are limiting factors to employing MSCs in these therapeutic strategies. Foremost is the lack of a general consensus on a definition of these cells, marring efforts to prepare homogeneous lots and more importantly complicating their in vitro and in vivo investigation. Furthermore, although one of the most profound clinical effects of MSC intravenous administration is the modulation of host immune responses, no adequate ex vivo assays exist to consistently predict the therapeutic effect of each MSC lot in the treated patient. Until these issues are addressed, this very promising and safe new therapeutic approach cannot be used to its full advantage. However, these confounding issues do present exciting opportunities. The first is an opportunity to discover unknown aspects of host immune responses because the unique effect driven by MSC infusion on a patient’s immunity has not yet been identified. In addition, there is an opportunity to develop methods, tests, and tools to better define MSCs and MSC-based therapy and provide consistency in preparation and effect. To this end, my laboratory recently developed a new approach to induce uniform pro-inflammatory MSC1 and anti-inflammatory MSC2 phenotypes from bone marrow-derived MSC preparations. I anticipate that MSC1 and MSC2 provide convenient tools with which to address some of these limitations and will help advance safe and effective CBTs for human disease.

 Graphical Abstract

Keywords

Anti-inflammatory ASC, adipose-derived multipotent stromal or mesenchymal stem cell Bioactive factors BM-MSC, bone marrow-derived multipotent stromal or mesenchymal stem cell Cell-based therapy Chemokines Cytokines Danger or stress responses HSC Hematopoietic stem cells IFN, interferon IL, interleukin Immune modulation or immunomodulating Immune response Immune suppression or immunosuppression MSC, multipotent stromal or mesenchymal stem cell MSC1, pro-inflammatory MSC phenotype MSC2, anti-inflammatory MSC phenotype Pro-inflammatory TLR, Toll-like receptors 

Abbreviations

ASC

Adipose-derived multipotent stromal or mesenchymal stem cell

BM-MSC

Bone marrow-derived multipotent stromal

COX

Cyclooxygenase

CTL

Cytotoxic T lymphocyte

ESCs

Embryonic stem cells

HLA

Human leukocyte antigen

HSCs

Hematopoietic stem cells

IDO

Indoleamine 2,3-dioxygenase

IFN

Interferon

IL

Interleukin

iNOS

Inducible nitric-oxide synthase

iPSCs

Induced pluripotent stem cells

LPS

Lipopolysaccharide

MHC

Major histocompatibility complex

MSC

Multipotent stromal or mesenchymal stem cell

MSC1

Pro-inflammatory MSC phenotype

MSC2

Anti-inflammatory MSC phenotype

NF

Nuclear factor

PGE-2

Prostaglandin E2

TGF

Transforming growth factor

TLR

Toll-like receptor

TNF

Tumor necrosis factor

Th1

T Helper cell 1

Treg

T Regulatory lymphocyte

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Notes

Acknowledgments

This work was supported by the National Institutes of Health grant 1P20RR20152-01, Department of Defense OC073102 Concept Award and research support from the Tulane Cancer Center and the Center for Stem Cell Research and Regenerative Medicine.

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© 2013 2012

Authors and Affiliations

  1. 1.Center for Stem Cell Research and Regenerative MedicineTulane UniversityNew OrleansUSA

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