Integrated transcriptomic, phenotypic, and functional study reveals tissue-specific immune properties of mesenchymal stromal cells

Abstract

Clinical-grade mesenchymal stromal cells (MSCs) can be expanded from bone marrow and adipose tissue to treat inflammatory diseases and degenerative disorders. However, the influence of their tissue of origin on their functional properties, including their immunosuppressive activity, remains unsolved. In this study, we produced paired bone marrow-derived mesenchymal stromal cell (BM-MSC) and adiposederived stromal cell (ASC) batches from 14 healthy donors. We then compared them using transcriptomic, phenotypic, and functional analyses and validated our results on purified native MSCs to infer which differences were really endowed by tissue of origin. Cultured MSCs segregated together owing to their tissue of origin based on their gene expression profile analyzed using differential expression and weighted gene coexpression network analysis. This translated into distinct immune-related gene signatures, phenotypes, and functional cell interactions. Importantly, sorted native BM-MSCs and ASCs essentially displayed the same distinctive patterns than their in vitro-expanded counterparts. As a whole, ASCs exhibited an immune profile consistent with a stronger inhibition of immune response and a lower immunogenicity, supporting the use of adipose tissue as a valuable source for clinical applications.

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

“…Their perivascular identity was revealed in both the basalis and functionalis ( Figures 2B,J), indicating that CD140b + CD146 + eMSC could be isolated from endometrial biopsies and would be shed in menstrual blood (Darzi et al, 2016). Gene profiling CD14b + CD146 + eMSC versus CD140b + CD146 − endometrial fibroblasts showed 762 differentially expressed genes (Spitzer et al, 2012), indicating that perivascular eMSC are distinct from endometrial fibroblasts as for other MSC types (Menard et al, 2020).…”

“…Counter arguments reiterate the importance of using the appropriate definition of the cells under study (i.e., perivascular MSC versus fibroblasts) (Galipeau et al, 2019). Integrated transcriptomic profiling of human MSC from different tissues show their segregation by tissue of origin (Roson-Burgo et al, 2016;Menard et al, 2020) and distinct tissue-specific MSC immune signatures that are similar between fresh and cultured MSC from the same tissue source (Menard et al, 2020). Herein we will distinguish between perivascular eMSC and endometrial stromal fibroblasts.…”

MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism

“…Besides, in order to succeed in prompting MSCs therapy into suitable clinical practices, the current major challenges reside in (i) MSCs manufacturing towards standardized and optimized culture processes, (ii) improving the MSCs characterization including multiscale and multiparametric analyses, (iii) developing dynamic potency tests to qualify MSCs batches that bring guaranties of their therapeutic potential, (iv) identifying from completed trials MSCs parameters correlated with clinical benefit in order to propose predictive markers for a given physiopathologic background. The study of MSCs biology over the last decade underlines that beyond their intrinsic potential (availability, tissue specificity (182), individual features from global multi-omic and phenotyping signatures) we have to estimate, for clinical purpose, their wide range of responses when facing a challenge. Their tissue function and therapeutic benefit indeed reside in this unique ability to map environmental cues, orchestrate local reactions with possible systemic consequences such as immunometabolism reprogramming.…”

Multi-Parameter Analysis of Biobanked Human Bone Marrow Stromal Cells Shows Little Influence for Donor Age and Mild Comorbidities on Phenotypic and Functional Properties

“…Different outcomes considering an in vivo imprint of the cell donor and tissue source may be obtained when using different starting materials (e.g., adipose or placental tissue instead of BM) (98). We have predominantly banked BM-MSCs at our facility so far, and we can thus not extend our analysis to MSCs derived from other tissue sources in the same depth.…”