1. Data against a Common Assumption: Xenogeneic Mouse Models Can Be Used to Assay Suppression of Immunity by Human MSCs 
Darwin J. Prockop, Joo Youn Oh, Ryang Hwa Lee 
Molecular Therapy 
Volume 25, Issue 8, Pages (August 2017)
DOI: /j.ymthe
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions

2. Figure 1
Summary of Major Differences between Expansion in Culture of mMSCs and hMSCs
aPhinney and associates4 developed an elegant protocol for expanding mMSCs without transformation by first immunodepleting the cultures of hematopoietic cells and then culturing them under an atmosphere of 5% oxygen. bExpansion at low density to enrich early progenitor cells defined as rapidly self-replicating MSCs or RS cells described by Lee et al.63 and in references therein. cVaries with preparations of different bone marrow aspirates taken from the same donor at the same session.
Molecular Therapy  , DOI: ( /j.ymthe )
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions

3. Figure 2 Summary of Immune-Suppressive Effects of hMSCs in Mice
(A) Data from experiments, in which 2 × 106 hMSCs were infused intravenously into immune-deficient mice (NOD/scid). The hMSCs were detected in tissues by qPCR assays for human-specific Alu sequences and by qRT-PCR assays specific for human GAPDH mRNA. For the RT-PCR assays, standards curves were prepared for each tissue (with hMSCs added to tissue from control mice) to correct for variability in extraction of mRNA and the efficiency of the polymerase reaction. (B) Data on hearts from experiments, in which 1 × 106 hMSCs were infused intravenously into immune-deficient mice (NOD/scid) right after permanent ligation of the left anterior descending coronary artery. Hearts were assayed as in (A). (A and B) from Lee et al.18 Reprinted with permission from Elsevier: Lee et al., Cell Stem Cell, 2009; 5: 59, Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6 (TNF-stimulated gene/protein-6). (C) Pharmokinetic analysis of the data in (A) by Parekkadan and Milwid.109 Solid blue line, apparent activity; dashed purple line, % of total cells remaining; dashed orange line, unit activity per cell; solid red line, therapeutic activity; dotted black line, minimum effective activity. Reprinted with permission from Annu. Rev. Biomed. Eng.: Parekkadan, B., and Milwid, J.M. Annu. Rev. Biomed. Eng. 2010;12:87, Mesenchymal stem cells as therapeutics. (D) In different immune models, the major immunosuppressive factors secreted by hMSCs were observed to be TSG-6, IL-1RA (IL-1 receptor antagonist), HO-1 (heme oxygenase 1), PGE2 (prostaglandin E2), TGF-β (tumor growth factor β), CCL2, IDO1 (indoleamine-pyrrole 2,3-dioxygenase 1), FasL (Fas ligand), or PD-L1 (programmed death-ligand 1). Most of the factors primarily altered cells of the innate immune system, such as monocytes/macrophages, MDSCs, or antigen presenting dendritic cells. Subsequent waves of cytokines then suppressed inflammation and altered T cells to either increase or decrease the ratio of Th1/Th17:Th2 responses.
Molecular Therapy  , DOI: ( /j.ymthe )
Copyright © 2017 The American Society of Gene and Cell Therapy Terms and Conditions