Mesenchymal stromal cells to control donor-specific memory T cells in solid organ transplantation

Abstract

Recent studies of MSCs in kidney transplantation highlight the anticipated add-on value of the immunomodulatory properties of bone marrow derived MSCs in persistently inhibiting donor-specific effector/memory CD8 T cells, an effect not shared by the current immunosuppressive drugs.

Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage

“…In brief, following previously published protocols [29,30], WT B6 mice were immunized subcutaneously (s.c.) with interphotoreceptor retinoid-binding protein peptide 1-20 (IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] in complete Freund's adjuvant (200 μg/mouse), then 2 weeks later, spleen cells were collected and re-stimulated with 10 μg/ml of IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] peptide in vitro, together with 10 ng/ml of IL-23 (Biolegend, CA). After 72 h of culture, blasting T cells were enriched by Ficoll centrifugation and adoptively transferred into naïve B6 mice by tail vein injection (5 × 10 6 /mouse), which were then randomly divided into 2 groups.…”

“…clinical studies as a potential therapy for many inflammatory diseases, such as graft versus host disease (GVHD) [4], multiple sclerosis [5], diabetes [6], colitis [7], and transplant rejection [8]. Despite all the efforts over the years and more than 400 registered MSC-based clinical trials (www.clinicaltrials.gov), there has been no approved MSC product in the US for treating inflammatory diseases.…”

Local Inhibition of Complement Improves Mesenchymal Stem Cell Viability and Function After Administration

“…5 Infusion of MSCs by intravenous injection is the most common delivery route in both humans and animals. Infusion of allo-or xeno-MSCs has been found to be effective in ameliorating pathological conditions in many animal models of disease, including multiple sclerosis, 6 rheumatoid arthritis, 7 myasthenia gravis, 8 diabetes, 9 inflammatory bowel disease, 10 and allograft rejection, 11 thus providing the rationale for testing the use of MSCs in clinical trials. However, in both human and animal studies, 5 it has been observed that most of the infused cells are first trapped in the lung, then some migrate out to other tissues and mysteriously disappear within a few days.…”

Strategies to improve the immunosuppressive properties of human mesenchymal stem cells

“…MSCs exposed to interferon (IFN)-γ are activated and suppress graft-versus-host disease (GVHD) in vivo [ 2 ]. Thus, the immunosuppressive properties of MSCs may be able to repair tissue damage caused by the immune system in autoimmune-induced inflammatory bowel diseases such as Crohn’s disease [ 32 ] and ulcerative colitis [ 33 ], treat GVHD of the gut, liver, and skin after allogeneic hematopoietic stem cell (HSC) transplantation [ 34 – 36 ], and prevent the rejection of organ transplants [ 37 , 38 ]. However, the detailed mechanisms underlying the therapeutic effects of MSCs, a heterogeneous population of ex vivo expanded cells [ 39 – 41 ], have not been fully elucidated.…”