Allogeneic Mesenchymal Stromal Cells (MSCs) are of Comparable Efficacy to Syngeneic MSCs for Therapeutic Revascularization in C57BKSdb/db Mice Despite the Induction of Alloantibody

Abstract

Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKS mice. Phosphate-buffered saline (control group), and MSCs (1 × 10) from B6 (allogeneic group) or C57BKS (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKS mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.

Mtu1 defects are correlated with reduced osteogenic differentiation

“…BM-MSCs were isolated from four-month-old mice to further investigate the influence of Mtu1 deficiency on MSC differentiation. These MSCs were purified by adherence to plastic and identified using expression of cell-surface markers, such as CD44 and Sca-1, and lack of expression of F4/80 and CD45 surface molecules 30 , 31 . As shown in Fig.…”

Development and validation of a multiparametric semi-quantitative scoring system for the histopathological assessment of ischaemia severity in skeletal muscle.

“…In the past years, there has been an increased interest in developing novel therapeutic products aiming to improve tissue perfusion and/or restoration of tissue function in these patients [25]. The mouse model of HLI is considered the most clinically relevant pre-clinical model of PAD, and especially CLI [26], and has been largely used to assess pre-clinical e cacy of cell therapy products such as mesenchymal stromal cells (MSCs) [27][28][29][30][31]. In most cases, a complete morphologic assessment of tissue using a range of histological techniques is performed for treatment group comparisons.…”

A Year in the Life of the EU-CardioRNA COST Action: CA17129 Catalysing Transcriptomics Research in Cardiovascular Disease

“…Another possible application of AI was presented by Mitja Lustrek from Slovenia focusing on the application of classification trees in the prediction of outcome in heart failure (HF) patients based on the clinical parameters. Tim O'Brien (IE) summarised their work on the therapeutic application of mesenchymal stromal cells to reduce diabetic complications [9].…”