Concise Review: The Surface Markers and Identity of Human Mesenchymal Stem Cells

Lv, Fengxiang; Tuan, Rocky S.; Cheung, Kenneth M.C.; Leung, Victor

doi:10.1002/stem.1681

Cited by 879 publications

(720 citation statements)

References 118 publications

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“…Although we tested fewer MSC lines expanded by this second manufacturing process, this result may indicate that morphological characterization must be performed with each manufacturing process to establish useful criteria for identifying MSC preparations with desired immunosuppressive potential. Similarly, MSCs from other tissue sources (adipose, umbilical cord, dental pulp) may possess tissue-specific morphological phenotypes and responses that will need to be characterized to identify potential morphological quality attributes unique to these cell types (42). As this study tested only three MSC lines produced by this second manufacturing process, further study will be required to confirm that unique morphological profiles are correlated with immunosuppressive capacity in bone marrowderived MSC lines produced by varying sources or manufacturing processes.…”

Section: Morphological Features Of Mscs After Ifn-γ Stimulation Corrementioning

confidence: 99%

Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity

Klinker

Marklein

Surdo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

168

166

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Human mesenchymal stromal cell (MSC) lines can vary significantly in their functional characteristics, and the effectiveness of MSCbased therapeutics may be realized by finding predictive features associated with MSC function. To identify features associated with immunosuppressive capacity in MSCs, we developed a robust in vitro assay that uses principal-component analysis to integrate multidimensional flow cytometry data into a single measurement of MSC-mediated inhibition of T-cell activation. We used this assay to correlate single-cell morphological data with overall immunosuppressive capacity in a cohort of MSC lines derived from different donors and manufacturing conditions. MSC morphology after IFN-γ stimulation significantly correlated with immunosuppressive capacity and accurately predicted the immunosuppressive capacity of MSC lines in a validation cohort. IFN-γ enhanced the immunosuppressive capacity of all MSC lines, and morphology predicted the magnitude of IFN-γ-enhanced immunosuppressive activity. Together, these data identify MSC morphology as a predictive feature of MSC immunosuppressive function.H uman mesenchymal stromal cells (MSCs) can potently suppress immune responses in vitro and in animal models of human disease (1, 2), but to date MSC-based therapies have produced mixed results in clinical trials for treatment of inflammatory and autoimmune diseases (3, 4). A major challenge in the development of consistently effective MSC-based immunosuppressive therapies is that MSC lines derived from different donors and manufacturing processes (i.e., cell expansion) can possess markedly dissimilar immunosuppressive function (3,5,6). Although methods exist to assess MSC immunosuppression in vitro, they are often based on only a few measured outcomes, assay culture conditions, and donor MSC samples (5, 7-9). To improve upon these methods, we developed an experimental and analytical approach to quantify MSC-mediated immune suppression using principal-component analysis (PCA) to integrate multiple measurements of T-cell activation assessed at a range of MSC densities. This approach allowed us to determine a single value for immunosuppressive capacity for MSC lines derived from two different manufacturing processes and 13 independent donors.Another major challenge associated with MSC-based immune therapies is the lack of well-defined predictive markers to identify MSC lines with therapeutically relevant biological activities or manufacturing processes that produce more effective MSCbased products. Efforts have been made to identify MSC quality attributes associated with immunosuppression (6, 7), but the majority of clinical studies (10) rely upon the surface markers described by Dominici et al. (11). Having previously shown that morphology can predict MSC mineralization capacity (12), we hypothesized that morphological features associated with immunosuppression in MSCs could be identified and used to predict their performance in our quantitative immunosuppression assay.Using our quantitative method for as...

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Section: Morphological Features Of Mscs After Ifn-γ Stimulation Corrementioning

confidence: 99%

Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity

Klinker

Marklein

Surdo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

168

166

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“…The latter terms are defined as plastic adherent cells that must express CD105, CD90, and CD73 but lack not only the expression of pan-leukocyte (CD45), endothelial, or primitive hematopoietic (CD34), monocyte (CD14 or CD11b), or B cell (CD79a or CD19) markers, but also the expression of HLA class II (HLA-DR) surface antigen, and show tri-lineage differentiation into osteoblasts, adipocytes, and chondrocytes [7].…”

mentioning

confidence: 99%

Stem cell therapy for inflammatory bowel disease

2015

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Inflammatory bowel disease (IBD) could be curable by ''immune rest'' and correction of the genetic predisposition inherent in allogeneic hematopoietic stem cell transplantation. However, balancing risks against benefits remains challenging. The application of mesenchymal stem cells (MSCs) serving as a site-regulated ''drugstore'' is a recent concept, which suggests the possibility of an alternative treatment for many intractable diseases such as IBD. Depending on the required function of MSC, such as a cell provider, immune moderator, and/or trophic resource, MSC therapy should be optimized to maximize its therapeutic benefit. Therapeutic effects do not always require full engraftment of MSCs. Therefore, optimization of pleiotropic gut trophic factors produced by MSCs, which favoring not only regulating immune responses but also promoting tissue repair, must directly enhance new drug discoveries for treatment of IBD. Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and patients. However, the translational arm of stem cell science remains in a relatively primitive state.Although several clinical studies using MSCs have been initiated, early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, and can be resolved only by scientifically unveiling the mechanisms of therapeutic action. In the present review, the authors outline how such information would facilitate the critical steps in the paradigm shift from basic research on stem cell biology to clinical practice of regenerative medicine for conquering IBD in the near future.

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“…The minimal criteria for defining MSCs include: (a) remain plastic-adherent under standard culture conditions; (b) express CD73, CD90, and CD105, and lack expression of CD34, CD45, CD14 or CD11b, CD79a or CD19, and HLA-DR surface molecules; and (c) differentiate into osteoblasts, adipocytes, and chondrocytes in vitro [83,84].…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

“…Originally isolated from bone marrow, MSCs have being isolated from other sites including spleen, thymus, muscle, adipose tissue, endometrium, placenta, umbilical cord, umbilical cord blood, peripheral blood, periosteum, periodontal ligament, dental pulp, synovium, synovial fluid, tendons, and cartilage [84,85]. A perivascular location for MSCs has been suggested, correlating these cells with pericytes.…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Chondrocyte Turnover in Lung Cartilage

Gopar-Cuevas¹,

Niderhauser‐García²,

Arellano³

et al. 2018

Cartilage Repair and Regeneration

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Cartilage is a highly differentiated connective tissue that forms mechanical support to soft tissues and is important for bone development from fetal period to puberty. It is conformed by chondrocytes and extracellular matrix. It is generally believed that adult cartilage has no capacity to renewal. A delicate balance between cell proliferation and cell death ensures the maintenance of normal tissue morphology and function. Stem cells play essential roles in this process. Mesenchymal stem cells (MSCs) can give rise to multiple lineages including bone, adipose and cartilage. Nestin protein was initially identified as a marker for neural stem cells, but its expression has also been detected in many types of cells, including MSCs. In vivo, chondrocyte turnover has been almost exclusively studied in articular cartilage. In this chapter we will review the findings about the chondrocyte turnover in lung cartilage. We have presented evidence that there exist nestinpositive MSCs in healthy adulthood that participates in the turnover of lung cartilage and in lung airway epithelium renewal. These findings may improve our knowledge about the biology of the cartilage and of the stem cells, and could provide new cell candidates for cartilage tissue engineering and for therapy for devastating pulmonary diseases.

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Concise Review: The Surface Markers and Identity of Human Mesenchymal Stem Cells

Cited by 879 publications

References 118 publications

Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity

Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity

Stem cell therapy for inflammatory bowel disease

Chondrocyte Turnover in Lung Cartilage

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