Mesenchymal Stromal Cells: Current Understanding and Clinical Status

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Multipotent mesenchymal stromal cells (MSCs) represent a rare heterogeneous subset of pluripotent stromal cells that can be isolated from many different adult tissues that exhibit the potential to give rise to cells of diverse lineages. Numerous studies have reported beneficial effects of MSCs in tissue repair and regeneration. After culture expansion and in vivo administration, MSCs home to and engraft to injured tissues and modulate the inflammatory response through synergistic downregulation of proinflammatory cytokines and upregulation of both prosurvival and antiinflammatory factors. In addition, MSCs possess remarkable immunosuppressive properties, suppressing T-cell, NK cell functions, and also modulating dentritic cell activities. Tremendous progress has been made in preclinical studies using MSCs, including the ability to use allogeneic cells, which has driven the application of MSCs toward the clinical setting. This review highlights our current understanding into the biology of MSCs with particular emphasis on the cardiovascular and renal applications, and provides a brief update on the clinical status of MSC-based therapy.

Related collections

Most cited references 81

Record: found
Abstract: found
Article: not found

Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation.

William Tse, John Pendleton, Wendy Beyer … (2003)

Marrow stromal cells (MSC) can differentiate into multiple mesenchymal tissues. To assess the feasibility of human MSC transplantation, we evaluated the in vitro immunogenicity of MSC and their ability to function as alloantigen presenting cells (APC). Human MSC were derived and used in mixed cell cultures with allogeneic peripheral blood mononuclear cells (PBMC). Expression of immunoregulatory molecules on MSC was analyzed by flow cytometry. An MSC-associated suppressive activity was analyzed using cell-proliferation assays and enzyme-linked immunoassays. MSC failed to elicit a proliferative response when cocultured with allogeneic PBMC, despite provision of a costimulatory signal delivered by an anti-CD28 antibody and pretreatment of MSC with gamma-interferon. MSC express major histocompatibility complex (MHC) class I and lymphocyte function-associated antigen (LFA)-3 antigens constitutively and MHC class II and intercellular adhesion molecule (ICAM)-1 antigens upon gamma-interferon treatment but do not express CD80, CD86, or CD40 costimulatory molecules. MSC actively suppressed proliferation of responder PBMC stimulated by third-party allogeneic PBMC as well as T cells stimulated by anti-CD3 and anti-CD28 antibodies. Separation of MSC and PBMC by a semipermeable membrane did not abrogate the suppression. The suppressive activity could not be accounted for by MSC production of interleukin-10, transforming growth factor-beta1, or prostaglandin E2, nor by tryptophan depletion of the culture medium. Human MSC fail to stimulate allogeneic PBMC or T-cell proliferation in mixed cell cultures. Unlike other nonprofessional APC, this failure of function is not reversed by provision of CD28-mediated costimulation nor gamma-interferon pretreatment. Rather, MSC actively inhibit T-cell proliferation, suggesting that allogeneic MSC transplantation might be accomplished without the need for significant host immunosuppression.

0 comments Cited 322 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms.

Florian Tögel, Zhuma Hu, Kathleen A. Weiss … (2005)

Severe acute renal failure (ARF) remains a common, largely treatment-resistant clinical problem with disturbingly high mortality rates. Therefore, we tested whether administration of multipotent mesenchymal stem cells (MSC) to anesthetized rats with ischemia-reperfusion-induced ARF (40-min bilateral renal pedicle clamping) could improve the outcome through amelioration of inflammatory, vascular, and apoptotic/necrotic manifestations of ischemic kidney injury. Accordingly, intracarotid administration of MSC (approximately 10(6)/animal) either immediately or 24 h after renal ischemia resulted in significantly improved renal function, higher proliferative and lower apoptotic indexes, as well as lower renal injury and unchanged leukocyte infiltration scores. Such renoprotection was not obtained with syngeneic fibroblasts. Using in vivo two-photon laser confocal microscopy, fluorescence-labeled MSC were detected early after injection in glomeruli, and low numbers attached at microvasculature sites. However, within 3 days of administration, none of the administered MSC had differentiated into a tubular or endothelial cell phenotype. At 24 h after injury, expression of proinflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma, and inducible nitric oxide synthase was significantly reduced and that of anti-inflammatory IL-10 and bFGF, TGF-alpha, and Bcl-2 was highly upregulated in treated kidneys. We conclude that the early, highly significant renoprotection obtained with MSC is of considerable therapeutic promise for the cell-based management of clinical ARF. The beneficial effects of MSC are primarily mediated via complex paracrine actions and not by their differentiation into target cells, which, as such, appears to be a more protracted response that may become important in late-stage organ repair.

0 comments Cited 308 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms.

T Kinnaird, E STABILE, M. Burnett … (2004)

We recently demonstrated that marrow stromal cells (MSCs) augment collateral remodeling through release of several cytokines such as VEGF and bFGF rather than via cell incorporation into new or remodeling vessels. The present study was designed to characterize the full spectrum of cytokine genes expressed by MSCs and to further examine the role of paracrine mechanisms that underpin their therapeutic potential. Normal human MSCs were cultured under normoxic or hypoxic conditions for 72 hours. The gene expression profile of the cells was determined using Affymetrix GeneChips representing 12 000 genes. A wide array of arteriogenic cytokine genes were expressed at baseline, and several were induced >1.5-fold by hypoxic stress. The gene array data were confirmed using ELISA assays and immunoblotting of the MSC conditioned media (MSC(CM)). MSC(CM) promoted in vitro proliferation and migration of endothelial cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partially attenuated these effects. Similarly, MSC(CM) promoted smooth muscle cell proliferation and migration in a dose-dependent manner. Using a murine hindlimb ischemia model, murine MSC(CM) enhanced collateral flow recovery and remodeling, improved limb function, reduced the incidence of autoamputation, and attenuated muscle atrophy compared with control media. These data indicate that paracrine signaling is an important mediator of bone marrow cell therapy in tissue ischemia, and that cell incorporation into vessels is not a prerequisite for their effects.

0 comments Cited 288 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Stem Cells

Journal ID (publisher-id): stem

Title: Stem Cells (Dayton, Ohio)

Publisher: Wiley Subscription Services, Inc., A Wiley Company

ISSN (Print): 1066-5099

ISSN (Electronic): 1549-4918

Publication date (Print): March 2010

Publication date (Electronic): 04 December 2009

Volume: 28

Issue: 3

Pages: 585-596

Affiliations

simpleCentre for Translational Medicine and Therapeutics, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary—University of London London, United Kingdom

Author notes

Centre for Translational Medicine and Therapeutics, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary–University of London, London, EC1M 6BQ, United Kingdom. Telephone: +44 207-882-8236; Fax: +44 207-882-8252; e-mail: h.salem@ 123456qmul.ac.uk

Author contributions: H.S.: Conception and design, collection and/or assembly of data, manuscript writing; C.T.: Final approval of manuscript.

Disclosure of potential conflicts of interest is found at the end of this article.

Article

DOI: 10.1002/stem.269

PMC ID: 2962904

PubMed ID: 19967788

SO-VID: c1d7f865-af6f-4a90-b9d2-90afaf720b07

License:

Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

Mesenchymal Stromal Cells: Current Understanding and Clinical Status

Read this article at

Abstract

Related collections

Universal stem cells

Most cited references 81

Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation.

Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms.

Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 982

Cited by 248

Most referenced authors 2,911